Elizabeth Mechcatie

Telmisartan was approved by the Food and Drug Administration for a new indication last month: reducing the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years or older who are at high risk of developing major cardiovascular events and cannot take ACE inhibitors.

Also approved by the FDA was a tablet formulation combining telmisartan with the calcium channel blocker amlodipine for treating hypertension.

Telmisartan, an angiotensin-II receptor blocker (ARB) marketed as Micardis, is manufactured by Boehringer Ingelheim Pharmaceuticals Inc. It was initially approved as an antihypertensive in 1998.

The revised label for telmisartan includes a statement that patients at high risk for cardiovascular (CV) events can use it with other needed treatments, such as antihypertensive, antiplatelet, or lipid-lowering therapy, but that use with an ACE inhibitor is not recommended. The approved dose for the cardiovascular risk reduction indication is 80 mg once daily.

The approval for CV risk reduction is supported by two studies involving patients aged 55 years and older who were at high CV risk, according to the revised label. In both, the primary end point was a composite of death from CV causes, MI, stroke, and hospitalization for heart failure; the secondary end point was a composite of CV death, MI, and stroke.

In ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial), which compared 80 mg of telmisartan, 10 mg of ramipril, or the combination in 25,620 patients who did not have a history of intolerance to ACE inhibitors, the incidence of the primary end point was similar in patients treated with telmisartan (16.7%) and those treated with ramipril (16.5%) over a mean of about 54 months.

In TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease), which compared 80 mg of telmisartan with placebo in almost 6,000 patients who had a history of intolerance to ACE inhibitors (mostly due to cough), the incidence of the primary end point was also similar in the two groups over a mean of 56 months: 15.7% among those on telmisartan and 17% among those on placebo. The incidence of the secondary end point, which did not include heart failure hospitalization, was significantly lower among those on telmisartan than in those on placebo (13% vs. 14.8%).

Although the rates of events in ONTARGET were similar between patients on telmisartan and those on ramipril, “the results did not unequivocally rule out that Micardis may not preserve a meaningful fraction of the effect of ramipril in reducing cardiovascular events,” the label states, but the results of both studies “do adequately support Micardis being more effective than placebo would be in this setting.”

The telmisartan-amlodipine combination tablet will be marketed under the trade name Twynsta, according to the company. There are four strengths: 40 mg of telmisartan with 5 mg or 10 mg of amlodipine and 80 mg of telmisartan with 5 mg or 10 mg of amlodipine.

Telmisartan was approved by the Food and Drug Administration for a new indication last month: reducing the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years or older who are at high risk of developing major cardiovascular events and cannot take ACE inhibitors.

Also approved by the FDA was a tablet formulation combining telmisartan with the calcium channel blocker amlodipine for treating hypertension.

Telmisartan, an angiotensin-II receptor blocker (ARB) marketed as Micardis, is manufactured by Boehringer Ingelheim Pharmaceuticals Inc. It was initially approved as an antihypertensive in 1998.

The revised label for telmisartan includes a statement that patients at high risk for cardiovascular (CV) events can use it with other needed treatments, such as antihypertensive, antiplatelet, or lipid-lowering therapy, but that use with an ACE inhibitor is not recommended. The approved dose for the cardiovascular risk reduction indication is 80 mg once daily.

The approval for CV risk reduction is supported by two studies involving patients aged 55 years and older who were at high CV risk, according to the revised label. In both, the primary end point was a composite of death from CV causes, MI, stroke, and hospitalization for heart failure; the secondary end point was a composite of CV death, MI, and stroke.

In ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial), which compared 80 mg of telmisartan, 10 mg of ramipril, or the combination in 25,620 patients who did not have a history of intolerance to ACE inhibitors, the incidence of the primary end point was similar in patients treated with telmisartan (16.7%) and those treated with ramipril (16.5%) over a mean of about 54 months.

In TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease), which compared 80 mg of telmisartan with placebo in almost 6,000 patients who had a history of intolerance to ACE inhibitors (mostly due to cough), the incidence of the primary end point was also similar in the two groups over a mean of 56 months: 15.7% among those on telmisartan and 17% among those on placebo. The incidence of the secondary end point, which did not include heart failure hospitalization, was significantly lower among those on telmisartan than in those on placebo (13% vs. 14.8%).

Although the rates of events in ONTARGET were similar between patients on telmisartan and those on ramipril, “the results did not unequivocally rule out that Micardis may not preserve a meaningful fraction of the effect of ramipril in reducing cardiovascular events,” the label states, but the results of both studies “do adequately support Micardis being more effective than placebo would be in this setting.”

The telmisartan-amlodipine combination tablet will be marketed under the trade name Twynsta, according to the company. There are four strengths: 40 mg of telmisartan with 5 mg or 10 mg of amlodipine and 80 mg of telmisartan with 5 mg or 10 mg of amlodipine.

Telmisartan was approved by the Food and Drug Administration for a new indication last month: reducing the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years or older who are at high risk of developing major cardiovascular events and cannot take ACE inhibitors.

Also approved by the FDA was a tablet formulation combining telmisartan with the calcium channel blocker amlodipine for treating hypertension.

Telmisartan, an angiotensin-II receptor blocker (ARB) marketed as Micardis, is manufactured by Boehringer Ingelheim Pharmaceuticals Inc. It was initially approved as an antihypertensive in 1998.

The revised label for telmisartan includes a statement that patients at high risk for cardiovascular (CV) events can use it with other needed treatments, such as antihypertensive, antiplatelet, or lipid-lowering therapy, but that use with an ACE inhibitor is not recommended. The approved dose for the cardiovascular risk reduction indication is 80 mg once daily.

The approval for CV risk reduction is supported by two studies involving patients aged 55 years and older who were at high CV risk, according to the revised label. In both, the primary end point was a composite of death from CV causes, MI, stroke, and hospitalization for heart failure; the secondary end point was a composite of CV death, MI, and stroke.

In ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial), which compared 80 mg of telmisartan, 10 mg of ramipril, or the combination in 25,620 patients who did not have a history of intolerance to ACE inhibitors, the incidence of the primary end point was similar in patients treated with telmisartan (16.7%) and those treated with ramipril (16.5%) over a mean of about 54 months.

In TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease), which compared 80 mg of telmisartan with placebo in almost 6,000 patients who had a history of intolerance to ACE inhibitors (mostly due to cough), the incidence of the primary end point was also similar in the two groups over a mean of 56 months: 15.7% among those on telmisartan and 17% among those on placebo. The incidence of the secondary end point, which did not include heart failure hospitalization, was significantly lower among those on telmisartan than in those on placebo (13% vs. 14.8%).

Although the rates of events in ONTARGET were similar between patients on telmisartan and those on ramipril, “the results did not unequivocally rule out that Micardis may not preserve a meaningful fraction of the effect of ramipril in reducing cardiovascular events,” the label states, but the results of both studies “do adequately support Micardis being more effective than placebo would be in this setting.”

The telmisartan-amlodipine combination tablet will be marketed under the trade name Twynsta, according to the company. There are four strengths: 40 mg of telmisartan with 5 mg or 10 mg of amlodipine and 80 mg of telmisartan with 5 mg or 10 mg of amlodipine.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a teleconference.

The Web site, AMAfluhelp.org

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member.

People can log in to the Web site or can participate anonymously and can “invite” family members and their physicians to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck, Microsoft, Minute Clinic, and the state of Colorado.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a teleconference.

The Web site, AMAfluhelp.org

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member.

People can log in to the Web site or can participate anonymously and can “invite” family members and their physicians to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck, Microsoft, Minute Clinic, and the state of Colorado.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a teleconference.

The Web site, AMAfluhelp.org

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member.

People can log in to the Web site or can participate anonymously and can “invite” family members and their physicians to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck, Microsoft, Minute Clinic, and the state of Colorado.

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.

The Food and Drug Administration's approval of ustekinumab for moderate to severe plaque psoriasis—the first interleukin-12 and −23 antagonist to be approved in the United States—is accompanied by requirements for a risk management plan and postmarketing studies that address uncertainties about the long-term safety of the biologic drug.

Ustekinumab was approved for the treatment of moderate to severe plaque psoriasis in adult patients (aged 18 and older) who are candidates for phototherapy or systemic therapy. Ustekinumab will be marketed by Centocor Inc. as Stelara.

Because of concerns over potential long-term risks of ustekinumab, which delayed approval, the FDA is requiring a risk evaluation and mitigation strategy (REMS) and postmarketing requirements that include a 5-year follow-up of patients in the clinical trials for malignancies, serious infections, and other serious adverse events; the enrollment of treated patients in a registry that will follow them for 8 years; and the establishment of a U.S.-based pregnancy registry.

Elements of the REMS include a communication plan targeted to health care providers, as well as a patient medication guide that explains the risks of treatment and will be distributed to patients with each prescription, including refills. The company is also required to provide the FDA with assessments of how well the REMS is working; such assessment will include evaluations of prescriber and patient understanding of the risks of treatment. Prescribers will also be evaluated in how well they select appropriate patients for treatment, according to the FDA's approval letter.

Ustekinumab “is the first drug that's based truly on a genetic defect recognized in psoriasis,” Dr. Alan Menter, chairman of the division of dermatology at Baylor University Medical Center in Dallas, said in an interview.

Although precisely how IL-12 and −23 contribute to the pathophysiology of psoriasis is not entirely understood, “the fact is that the shared protein between them has a key role in the inflammatory aspect of psoriasis … and we now have a drug that specifically targets that,” he noted.

The most attractive features of this drug are rapid efficacy; “maintenance, if not improvement” of efficacy in most patients with continued treatment, especially through week 24 and beyond; and the convenient dosing schedule, which is every 12 weeks after the first two doses given 4 weeks apart, Dr. Menter said. Long-term safety is the “big unknown,” so 5-year follow-up data are needed, he said.

Risk is a particular concern because of what happened to the biologic efalizumab (Raptiva), which was taken off the market after three cases of progressive multifocal leukoencephalopathy (PML), a progressive and often fatal brain infection, were reported in patients who were treated with the drug for psoriasis, including two fatal cases.

Another concern is that a significant proportion of psoriasis patients weigh more than 220 pounds and thus need the higher dose, which could be financially difficult for some patients, he added.

Dr. Menter was an investigator in clinical trials of ustekinumab, and is an investigator in phase III clinical trials of ABT-874, another IL-12 and −23 antagonist for psoriasis that is being manufactured by Abbott. He said he has no financial ties to Centocor or Abbott.

The first two doses of ustekinumab are administered subcutaneously, 4 weeks apart, after which it is administered every 12 weeks; a 45-mg dose is recommended for those weighing 220 pounds or less, and 90 mg for those heavier than 220 pounds. Ustekinumab must be administered under the supervision of a physician.

At a June 2008 meeting of the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee, which backed the approval of ustekinumab, most of the panel favored office-based administration because it would provide an opportunity for clinicians to evaluate patients for responses and side effects every 3 months, and would help collect postmarketing data.

The wholesaler's acquisition cost or list price for a 45-mg vial of ustekinumab is $4,663, according to Brian Kenney, a spokesperson for Centocor.

FDA approval was based primarily on two pivotal studies (PHOENIX I and PHOENIX II) of almost 2,000 patients, aged 18 years and older, who had plaque psoriasis and a PASI (Psoriasis Area and Severity Index) score of 12 or greater, with at least 10% surface body involvement. At 12 weeks, 67% of those on the 45-mg dose and 66%-76% of those on the 90-mg dose had achieved a least a 75% reduction in psoriasis as measured by their PASI 75 response, compared with 4% of those on placebo. Response rates among those who weighed less than 220 pounds showed similar response to both doses, but those who were heavier than 220 pounds had better response rates with the higher dose.

Dr. Menter described the efficacy data as “very compelling,” noting that at week 24 (8 weeks after the third injection), almost 50% of patients achieved a PASI 90.

As with the tumor necrosis factor blockers, the ustekinumab label includes warnings and precautions about the risk of serious infections and the possible increased risk of malignancies. Serious infections—including some that required hospitalization—have been reported in patients on ustekinumab. There has been one report of reversible posterior leukoencephalopathy syndrome (RPLS), a rare, potentially fatal neurologic disorder that is not caused by demyelination or a known infectious agent, according to the ustekinumab label. If RPLS is suspected, ustekinumab should be discontinued immediately and the patient should be treated.

Among the manufacturer's other postmarketing requirements is to enroll 4,000 ustekinumab-treated patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR), and follow them for 8 years for serious infections, tuberculosis, opportunistic infections, malignancy, hypersensitivity reactions, autoimmune diseases, and neurologic or demyelinating diseases.

Dr. Menter is cochair of PSOLAR.

Ustekinumab 'is the first drug that's based truly on a genetic defect recognized in psoriasis.'

Source DR. MENTER

The Food and Drug Administration's approval of ustekinumab for moderate to severe plaque psoriasis—the first interleukin-12 and −23 antagonist to be approved in the United States—is accompanied by requirements for a risk management plan and postmarketing studies that address uncertainties about the long-term safety of the biologic drug.

Ustekinumab was approved for the treatment of moderate to severe plaque psoriasis in adult patients (aged 18 and older) who are candidates for phototherapy or systemic therapy. Ustekinumab will be marketed by Centocor Inc. as Stelara.

Because of concerns over potential long-term risks of ustekinumab, which delayed approval, the FDA is requiring a risk evaluation and mitigation strategy (REMS) and postmarketing requirements that include a 5-year follow-up of patients in the clinical trials for malignancies, serious infections, and other serious adverse events; the enrollment of treated patients in a registry that will follow them for 8 years; and the establishment of a U.S.-based pregnancy registry.

Elements of the REMS include a communication plan targeted to health care providers, as well as a patient medication guide that explains the risks of treatment and will be distributed to patients with each prescription, including refills. The company is also required to provide the FDA with assessments of how well the REMS is working; such assessment will include evaluations of prescriber and patient understanding of the risks of treatment. Prescribers will also be evaluated in how well they select appropriate patients for treatment, according to the FDA's approval letter.

Ustekinumab “is the first drug that's based truly on a genetic defect recognized in psoriasis,” Dr. Alan Menter, chairman of the division of dermatology at Baylor University Medical Center in Dallas, said in an interview.

Although precisely how IL-12 and −23 contribute to the pathophysiology of psoriasis is not entirely understood, “the fact is that the shared protein between them has a key role in the inflammatory aspect of psoriasis … and we now have a drug that specifically targets that,” he noted.

The most attractive features of this drug are rapid efficacy; “maintenance, if not improvement” of efficacy in most patients with continued treatment, especially through week 24 and beyond; and the convenient dosing schedule, which is every 12 weeks after the first two doses given 4 weeks apart, Dr. Menter said. Long-term safety is the “big unknown,” so 5-year follow-up data are needed, he said.

Risk is a particular concern because of what happened to the biologic efalizumab (Raptiva), which was taken off the market after three cases of progressive multifocal leukoencephalopathy (PML), a progressive and often fatal brain infection, were reported in patients who were treated with the drug for psoriasis, including two fatal cases.

Another concern is that a significant proportion of psoriasis patients weigh more than 220 pounds and thus need the higher dose, which could be financially difficult for some patients, he added.

Dr. Menter was an investigator in clinical trials of ustekinumab, and is an investigator in phase III clinical trials of ABT-874, another IL-12 and −23 antagonist for psoriasis that is being manufactured by Abbott. He said he has no financial ties to Centocor or Abbott.

The first two doses of ustekinumab are administered subcutaneously, 4 weeks apart, after which it is administered every 12 weeks; a 45-mg dose is recommended for those weighing 220 pounds or less, and 90 mg for those heavier than 220 pounds. Ustekinumab must be administered under the supervision of a physician.

At a June 2008 meeting of the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee, which backed the approval of ustekinumab, most of the panel favored office-based administration because it would provide an opportunity for clinicians to evaluate patients for responses and side effects every 3 months, and would help collect postmarketing data.

The wholesaler's acquisition cost or list price for a 45-mg vial of ustekinumab is $4,663, according to Brian Kenney, a spokesperson for Centocor.

FDA approval was based primarily on two pivotal studies (PHOENIX I and PHOENIX II) of almost 2,000 patients, aged 18 years and older, who had plaque psoriasis and a PASI (Psoriasis Area and Severity Index) score of 12 or greater, with at least 10% surface body involvement. At 12 weeks, 67% of those on the 45-mg dose and 66%-76% of those on the 90-mg dose had achieved a least a 75% reduction in psoriasis as measured by their PASI 75 response, compared with 4% of those on placebo. Response rates among those who weighed less than 220 pounds showed similar response to both doses, but those who were heavier than 220 pounds had better response rates with the higher dose.

Dr. Menter described the efficacy data as “very compelling,” noting that at week 24 (8 weeks after the third injection), almost 50% of patients achieved a PASI 90.

As with the tumor necrosis factor blockers, the ustekinumab label includes warnings and precautions about the risk of serious infections and the possible increased risk of malignancies. Serious infections—including some that required hospitalization—have been reported in patients on ustekinumab. There has been one report of reversible posterior leukoencephalopathy syndrome (RPLS), a rare, potentially fatal neurologic disorder that is not caused by demyelination or a known infectious agent, according to the ustekinumab label. If RPLS is suspected, ustekinumab should be discontinued immediately and the patient should be treated.

Among the manufacturer's other postmarketing requirements is to enroll 4,000 ustekinumab-treated patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR), and follow them for 8 years for serious infections, tuberculosis, opportunistic infections, malignancy, hypersensitivity reactions, autoimmune diseases, and neurologic or demyelinating diseases.

Dr. Menter is cochair of PSOLAR.

Ustekinumab 'is the first drug that's based truly on a genetic defect recognized in psoriasis.'

Source DR. MENTER

The Food and Drug Administration's approval of ustekinumab for moderate to severe plaque psoriasis—the first interleukin-12 and −23 antagonist to be approved in the United States—is accompanied by requirements for a risk management plan and postmarketing studies that address uncertainties about the long-term safety of the biologic drug.

Ustekinumab was approved for the treatment of moderate to severe plaque psoriasis in adult patients (aged 18 and older) who are candidates for phototherapy or systemic therapy. Ustekinumab will be marketed by Centocor Inc. as Stelara.

Because of concerns over potential long-term risks of ustekinumab, which delayed approval, the FDA is requiring a risk evaluation and mitigation strategy (REMS) and postmarketing requirements that include a 5-year follow-up of patients in the clinical trials for malignancies, serious infections, and other serious adverse events; the enrollment of treated patients in a registry that will follow them for 8 years; and the establishment of a U.S.-based pregnancy registry.

Elements of the REMS include a communication plan targeted to health care providers, as well as a patient medication guide that explains the risks of treatment and will be distributed to patients with each prescription, including refills. The company is also required to provide the FDA with assessments of how well the REMS is working; such assessment will include evaluations of prescriber and patient understanding of the risks of treatment. Prescribers will also be evaluated in how well they select appropriate patients for treatment, according to the FDA's approval letter.

Ustekinumab “is the first drug that's based truly on a genetic defect recognized in psoriasis,” Dr. Alan Menter, chairman of the division of dermatology at Baylor University Medical Center in Dallas, said in an interview.

Although precisely how IL-12 and −23 contribute to the pathophysiology of psoriasis is not entirely understood, “the fact is that the shared protein between them has a key role in the inflammatory aspect of psoriasis … and we now have a drug that specifically targets that,” he noted.

The most attractive features of this drug are rapid efficacy; “maintenance, if not improvement” of efficacy in most patients with continued treatment, especially through week 24 and beyond; and the convenient dosing schedule, which is every 12 weeks after the first two doses given 4 weeks apart, Dr. Menter said. Long-term safety is the “big unknown,” so 5-year follow-up data are needed, he said.

Risk is a particular concern because of what happened to the biologic efalizumab (Raptiva), which was taken off the market after three cases of progressive multifocal leukoencephalopathy (PML), a progressive and often fatal brain infection, were reported in patients who were treated with the drug for psoriasis, including two fatal cases.

Another concern is that a significant proportion of psoriasis patients weigh more than 220 pounds and thus need the higher dose, which could be financially difficult for some patients, he added.

Dr. Menter was an investigator in clinical trials of ustekinumab, and is an investigator in phase III clinical trials of ABT-874, another IL-12 and −23 antagonist for psoriasis that is being manufactured by Abbott. He said he has no financial ties to Centocor or Abbott.

The first two doses of ustekinumab are administered subcutaneously, 4 weeks apart, after which it is administered every 12 weeks; a 45-mg dose is recommended for those weighing 220 pounds or less, and 90 mg for those heavier than 220 pounds. Ustekinumab must be administered under the supervision of a physician.

At a June 2008 meeting of the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee, which backed the approval of ustekinumab, most of the panel favored office-based administration because it would provide an opportunity for clinicians to evaluate patients for responses and side effects every 3 months, and would help collect postmarketing data.

The wholesaler's acquisition cost or list price for a 45-mg vial of ustekinumab is $4,663, according to Brian Kenney, a spokesperson for Centocor.

FDA approval was based primarily on two pivotal studies (PHOENIX I and PHOENIX II) of almost 2,000 patients, aged 18 years and older, who had plaque psoriasis and a PASI (Psoriasis Area and Severity Index) score of 12 or greater, with at least 10% surface body involvement. At 12 weeks, 67% of those on the 45-mg dose and 66%-76% of those on the 90-mg dose had achieved a least a 75% reduction in psoriasis as measured by their PASI 75 response, compared with 4% of those on placebo. Response rates among those who weighed less than 220 pounds showed similar response to both doses, but those who were heavier than 220 pounds had better response rates with the higher dose.

Dr. Menter described the efficacy data as “very compelling,” noting that at week 24 (8 weeks after the third injection), almost 50% of patients achieved a PASI 90.

As with the tumor necrosis factor blockers, the ustekinumab label includes warnings and precautions about the risk of serious infections and the possible increased risk of malignancies. Serious infections—including some that required hospitalization—have been reported in patients on ustekinumab. There has been one report of reversible posterior leukoencephalopathy syndrome (RPLS), a rare, potentially fatal neurologic disorder that is not caused by demyelination or a known infectious agent, according to the ustekinumab label. If RPLS is suspected, ustekinumab should be discontinued immediately and the patient should be treated.

Among the manufacturer's other postmarketing requirements is to enroll 4,000 ustekinumab-treated patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR), and follow them for 8 years for serious infections, tuberculosis, opportunistic infections, malignancy, hypersensitivity reactions, autoimmune diseases, and neurologic or demyelinating diseases.

Dr. Menter is cochair of PSOLAR.

Ustekinumab 'is the first drug that's based truly on a genetic defect recognized in psoriasis.'

Source DR. MENTER

BETHESDA, MD. — A Food and Drug Administration advisory panel cast mixed votes on whether data on an injectable product derived from autologous fibroblast cells had demonstrated that it was safe and effective for treating moderate to severe nasolabial fold wrinkles in adults, the indication for which it is under review for approval.

At the meeting, the FDA's Cellular, Tissue and Gene Therapies Advisory Committee voted 11-3 that the data submitted by the manufacturer showed the product was effective in treating moderate to severe nasolabial fold wrinkles. Dr. Michael Olding, the panel's plastic surgeon and chief of plastic surgery at George Washington University, Washington, voted yes on the efficacy question, but emphasized that the indication was narrow and the product had not been shown to be effective in treating the nasolabial fold or contour deficiencies. He and the other panelists also said that they did not believe the agent had been shown to be effective in people over age 65 years, in nonwhite populations, or in older men, who were not well represented in the two pivotal trials. The efficacy had been seen primarily in white women under age 65 years, who accounted for most of the patients.

The panel also voted 8-6 that the data on the product, azfibrocel-T, had not demonstrated that it was safe for the indication, citing gaps in the data, including uncertainty over its mechanism of action and whether it induced scar formation or collagen production.

Other safety concerns included not knowing what happens to the fibroblasts over time and the lack of biopsies to help make that determination, as well as the lack of long-term data and the likelihood that, once approved, it would be widely used off-label, and there are no data to support other uses. The panel, however, did not appear overly concerned about the potential tumorigenicity of the product, although they said longer term data were needed to address this theoretical risk. The panel was not asked specifically whether to recommend approval.

The product, previously called Isolagen, was marketed commercially in the United States between 1995 and 1999 as a nonregulated product, and in the United Kingdom between 2002 and 2007. It is manufactured by Fibrocell Science Inc., which until August was Isolagen Technologies Inc. If approved, the product will be marketed as Laviv.

Azfibrocel-T is derived from fibroblasts obtained from three punch biopsies taken from behind the ear that are sent to a Fibrocell facility. Once there, they are isolated, harvested, prepared in an injectable cell suspension, frozen, and shipped to clinicians overnight, for use within 48 hours. The cells are harvested an average of 50 days after the biopsies, according to the company.

Treatment is administered in three doses at 5-week intervals and is injected with a 29-guage needle directly into the papillary dermis of the nasolabial fold wrinkles, where the fibroblasts “are believed to produce and organize extracellular matrix proteins, including collagen, by a mechanism analogous to natural wound healing,” according to the company.

In the two pivotal, identical U.S. multicenter, double-blind trials, a total of 421 patients were randomized to receive three injections of azfibrocel-T or vehicle to the nasolabial fold wrinkles. Patients' mean age was 56 years, and most were white women.

At 6 months after the first treatment, significantly more of the patients who received the active treatment evaluated themselves as having a 2-point improvement in a 5-point scale evaluating the appearance of the “lower part of their face,” when compared with those who had received the vehicle (57% and 46% of those who received azfibrocel-T in both studies, compared with 30% and 8%, respectively, among those in the vehicle groups). This was one of the two primary endpoints.

The second primary endpoint was a 2-point improvement on the Lemperle scale as assessed by a blinded evaluator's live assessment at the 6-month visit, using a photo guide of the scale. When enrolled, patients' wrinkles were at least a grade 3 (moderately deep) on the 6-point scale that ranges from 0 (no wrinkle) to 5.

The differences in evaluator assessments of the azfibrocel-T–treated patients and those who received the vehicle were not as wide as the patients' assessments, but were statistically significant. At 6 months, 33% of the patients in one study and 19% in the second study were evaluated as having a 2-point improvement, compared with 7% of those on the vehicle in both studies.

The most common adverse events associated with treatment were injection site reactions, namely erythema, swelling, bruising, and bleeding; these effects were mostly mild to moderate and did not last longer than 7–14 days. There was one case of a basal cell carcinoma near the injection site diagnosed 5 months after the third treatment. Clinical experience to date indicates the risk of scarring and keloids is minimal, according to the company, which has proposed plans for a mandatory physician training program.

Voting no on both efficacy and safety, panelist Dr. Lynn A. Drake of Harvard Medical School, Boston, said she was concerned about the lack of nonvisible evidence to support safety. She and other dermatologists on the panel said that it was important to determine whether normal or scar tissue was present after treatment, whether collagen was produced, and if so, what type, and whether elastin was affected.

Dr. Drake questioned whether the lack of efficacy in people over age 65 was indicative of the inability of the elderly to scar, and emphasized that once a new treatment for wrinkles becomes available, it is widely used immediately in all age groups and often in locations where it might not be safe.

If approved, azfibrocel-T would be the first cellular product for treating nasolabial fold wrinkles and the first fibroblast product contained in an injectable cell suspension, according to the FDA. It would be the second autologous cell product to be approved; the first is Carticel, a preparation of autologous chondrocytes used to repair knee cartilage. Clinical studies are underway in facial acne scars, gingival recession, and vocal fold scarring. A study in burn scars is being planned, the company said.

The FDA usually follows the recommendations of its advisory panels.

BETHESDA, MD. — A Food and Drug Administration advisory panel cast mixed votes on whether data on an injectable product derived from autologous fibroblast cells had demonstrated that it was safe and effective for treating moderate to severe nasolabial fold wrinkles in adults, the indication for which it is under review for approval.

At the meeting, the FDA's Cellular, Tissue and Gene Therapies Advisory Committee voted 11-3 that the data submitted by the manufacturer showed the product was effective in treating moderate to severe nasolabial fold wrinkles. Dr. Michael Olding, the panel's plastic surgeon and chief of plastic surgery at George Washington University, Washington, voted yes on the efficacy question, but emphasized that the indication was narrow and the product had not been shown to be effective in treating the nasolabial fold or contour deficiencies. He and the other panelists also said that they did not believe the agent had been shown to be effective in people over age 65 years, in nonwhite populations, or in older men, who were not well represented in the two pivotal trials. The efficacy had been seen primarily in white women under age 65 years, who accounted for most of the patients.

The panel also voted 8-6 that the data on the product, azfibrocel-T, had not demonstrated that it was safe for the indication, citing gaps in the data, including uncertainty over its mechanism of action and whether it induced scar formation or collagen production.

Other safety concerns included not knowing what happens to the fibroblasts over time and the lack of biopsies to help make that determination, as well as the lack of long-term data and the likelihood that, once approved, it would be widely used off-label, and there are no data to support other uses. The panel, however, did not appear overly concerned about the potential tumorigenicity of the product, although they said longer term data were needed to address this theoretical risk. The panel was not asked specifically whether to recommend approval.

The product, previously called Isolagen, was marketed commercially in the United States between 1995 and 1999 as a nonregulated product, and in the United Kingdom between 2002 and 2007. It is manufactured by Fibrocell Science Inc., which until August was Isolagen Technologies Inc. If approved, the product will be marketed as Laviv.

Azfibrocel-T is derived from fibroblasts obtained from three punch biopsies taken from behind the ear that are sent to a Fibrocell facility. Once there, they are isolated, harvested, prepared in an injectable cell suspension, frozen, and shipped to clinicians overnight, for use within 48 hours. The cells are harvested an average of 50 days after the biopsies, according to the company.

Treatment is administered in three doses at 5-week intervals and is injected with a 29-guage needle directly into the papillary dermis of the nasolabial fold wrinkles, where the fibroblasts “are believed to produce and organize extracellular matrix proteins, including collagen, by a mechanism analogous to natural wound healing,” according to the company.

In the two pivotal, identical U.S. multicenter, double-blind trials, a total of 421 patients were randomized to receive three injections of azfibrocel-T or vehicle to the nasolabial fold wrinkles. Patients' mean age was 56 years, and most were white women.

At 6 months after the first treatment, significantly more of the patients who received the active treatment evaluated themselves as having a 2-point improvement in a 5-point scale evaluating the appearance of the “lower part of their face,” when compared with those who had received the vehicle (57% and 46% of those who received azfibrocel-T in both studies, compared with 30% and 8%, respectively, among those in the vehicle groups). This was one of the two primary endpoints.

The second primary endpoint was a 2-point improvement on the Lemperle scale as assessed by a blinded evaluator's live assessment at the 6-month visit, using a photo guide of the scale. When enrolled, patients' wrinkles were at least a grade 3 (moderately deep) on the 6-point scale that ranges from 0 (no wrinkle) to 5.

The differences in evaluator assessments of the azfibrocel-T–treated patients and those who received the vehicle were not as wide as the patients' assessments, but were statistically significant. At 6 months, 33% of the patients in one study and 19% in the second study were evaluated as having a 2-point improvement, compared with 7% of those on the vehicle in both studies.

The most common adverse events associated with treatment were injection site reactions, namely erythema, swelling, bruising, and bleeding; these effects were mostly mild to moderate and did not last longer than 7–14 days. There was one case of a basal cell carcinoma near the injection site diagnosed 5 months after the third treatment. Clinical experience to date indicates the risk of scarring and keloids is minimal, according to the company, which has proposed plans for a mandatory physician training program.

Voting no on both efficacy and safety, panelist Dr. Lynn A. Drake of Harvard Medical School, Boston, said she was concerned about the lack of nonvisible evidence to support safety. She and other dermatologists on the panel said that it was important to determine whether normal or scar tissue was present after treatment, whether collagen was produced, and if so, what type, and whether elastin was affected.

Dr. Drake questioned whether the lack of efficacy in people over age 65 was indicative of the inability of the elderly to scar, and emphasized that once a new treatment for wrinkles becomes available, it is widely used immediately in all age groups and often in locations where it might not be safe.

If approved, azfibrocel-T would be the first cellular product for treating nasolabial fold wrinkles and the first fibroblast product contained in an injectable cell suspension, according to the FDA. It would be the second autologous cell product to be approved; the first is Carticel, a preparation of autologous chondrocytes used to repair knee cartilage. Clinical studies are underway in facial acne scars, gingival recession, and vocal fold scarring. A study in burn scars is being planned, the company said.

The FDA usually follows the recommendations of its advisory panels.

BETHESDA, MD. — A Food and Drug Administration advisory panel cast mixed votes on whether data on an injectable product derived from autologous fibroblast cells had demonstrated that it was safe and effective for treating moderate to severe nasolabial fold wrinkles in adults, the indication for which it is under review for approval.

At the meeting, the FDA's Cellular, Tissue and Gene Therapies Advisory Committee voted 11-3 that the data submitted by the manufacturer showed the product was effective in treating moderate to severe nasolabial fold wrinkles. Dr. Michael Olding, the panel's plastic surgeon and chief of plastic surgery at George Washington University, Washington, voted yes on the efficacy question, but emphasized that the indication was narrow and the product had not been shown to be effective in treating the nasolabial fold or contour deficiencies. He and the other panelists also said that they did not believe the agent had been shown to be effective in people over age 65 years, in nonwhite populations, or in older men, who were not well represented in the two pivotal trials. The efficacy had been seen primarily in white women under age 65 years, who accounted for most of the patients.

The panel also voted 8-6 that the data on the product, azfibrocel-T, had not demonstrated that it was safe for the indication, citing gaps in the data, including uncertainty over its mechanism of action and whether it induced scar formation or collagen production.

Other safety concerns included not knowing what happens to the fibroblasts over time and the lack of biopsies to help make that determination, as well as the lack of long-term data and the likelihood that, once approved, it would be widely used off-label, and there are no data to support other uses. The panel, however, did not appear overly concerned about the potential tumorigenicity of the product, although they said longer term data were needed to address this theoretical risk. The panel was not asked specifically whether to recommend approval.

The product, previously called Isolagen, was marketed commercially in the United States between 1995 and 1999 as a nonregulated product, and in the United Kingdom between 2002 and 2007. It is manufactured by Fibrocell Science Inc., which until August was Isolagen Technologies Inc. If approved, the product will be marketed as Laviv.

Azfibrocel-T is derived from fibroblasts obtained from three punch biopsies taken from behind the ear that are sent to a Fibrocell facility. Once there, they are isolated, harvested, prepared in an injectable cell suspension, frozen, and shipped to clinicians overnight, for use within 48 hours. The cells are harvested an average of 50 days after the biopsies, according to the company.

Treatment is administered in three doses at 5-week intervals and is injected with a 29-guage needle directly into the papillary dermis of the nasolabial fold wrinkles, where the fibroblasts “are believed to produce and organize extracellular matrix proteins, including collagen, by a mechanism analogous to natural wound healing,” according to the company.

In the two pivotal, identical U.S. multicenter, double-blind trials, a total of 421 patients were randomized to receive three injections of azfibrocel-T or vehicle to the nasolabial fold wrinkles. Patients' mean age was 56 years, and most were white women.

At 6 months after the first treatment, significantly more of the patients who received the active treatment evaluated themselves as having a 2-point improvement in a 5-point scale evaluating the appearance of the “lower part of their face,” when compared with those who had received the vehicle (57% and 46% of those who received azfibrocel-T in both studies, compared with 30% and 8%, respectively, among those in the vehicle groups). This was one of the two primary endpoints.

The second primary endpoint was a 2-point improvement on the Lemperle scale as assessed by a blinded evaluator's live assessment at the 6-month visit, using a photo guide of the scale. When enrolled, patients' wrinkles were at least a grade 3 (moderately deep) on the 6-point scale that ranges from 0 (no wrinkle) to 5.

The differences in evaluator assessments of the azfibrocel-T–treated patients and those who received the vehicle were not as wide as the patients' assessments, but were statistically significant. At 6 months, 33% of the patients in one study and 19% in the second study were evaluated as having a 2-point improvement, compared with 7% of those on the vehicle in both studies.

The most common adverse events associated with treatment were injection site reactions, namely erythema, swelling, bruising, and bleeding; these effects were mostly mild to moderate and did not last longer than 7–14 days. There was one case of a basal cell carcinoma near the injection site diagnosed 5 months after the third treatment. Clinical experience to date indicates the risk of scarring and keloids is minimal, according to the company, which has proposed plans for a mandatory physician training program.

Voting no on both efficacy and safety, panelist Dr. Lynn A. Drake of Harvard Medical School, Boston, said she was concerned about the lack of nonvisible evidence to support safety. She and other dermatologists on the panel said that it was important to determine whether normal or scar tissue was present after treatment, whether collagen was produced, and if so, what type, and whether elastin was affected.

Dr. Drake questioned whether the lack of efficacy in people over age 65 was indicative of the inability of the elderly to scar, and emphasized that once a new treatment for wrinkles becomes available, it is widely used immediately in all age groups and often in locations where it might not be safe.

If approved, azfibrocel-T would be the first cellular product for treating nasolabial fold wrinkles and the first fibroblast product contained in an injectable cell suspension, according to the FDA. It would be the second autologous cell product to be approved; the first is Carticel, a preparation of autologous chondrocytes used to repair knee cartilage. Clinical studies are underway in facial acne scars, gingival recession, and vocal fold scarring. A study in burn scars is being planned, the company said.

The FDA usually follows the recommendations of its advisory panels.

Health care providers can now make use of 13 performance measures with which to assess adult patients' risk for cardiovascular disease.

These measures, which apply to adult patients aged 18 years and older, are not guidelines, but they translate existing guidelines for CVD prevention into steps that health care providers can easily use in their offices, according to Dr. Rita Redberg, professor of medicine, University of California, San Francisco, and the chairwoman of the writing committee (Circulation 2009;120:1296-336; J. Am. Coll. Cardiol. 2009;54:1364-405).

The measures were developed by the American College of Cardiology Foundation/American Heart Association task force on Performance Measures, in collaboration with the American Academy of Family Physicians, American Association of Cardiovascular and Pulmonary Rehabilitation, and Preventive Cardiovascular Nurses Association. They were endorsed by the American College of Preventive Medicine, American College of Sports Medicine, and Society for Women's Health Research.

The task force used guidelines supported by the strongest level of evidence, “the ones we really think make a difference in terms of patient care and patient outcomes,” Dr. Redberg, director of women's cardiovascular services at UCSF Medical Center, said in an interview.

The lifestyle/risk factor screening performance measure, for example, entails an assessment of lifestyle and risk factors for development of CVD; the second measure on the list, dietary intake counseling, provides advice about maintaining a healthy diet.

The remaining 11 performance measures are as follows: physical activity counseling; smoking/tobacco use; smoking/tobacco cessation; weight/adiposity assessment; weight management; blood pressure management; blood pressure control; blood lipid measurement; blood lipid therapy and control; global risk estimation; and aspirin use. The Global Risk evaluation measure entails use of a multivariate risk score to estimate a patient's absolute risk for development of CVD.

Several appendices are included with useful references, such as a sample performance measure survey form, a sample data collection flow sheet, a table for calculating body mass index, and a guideline on how to measure waist circumference.

The task force is hopeful that the table will be a useful reference in the office. Incorporating the measures into electronic medical records would be the most practical and efficient approach, but she said the measures were designed to be accessible and user friendly for offices that use only paper records, said Dr. Redberg, who had no conflicts to disclose.

Web Site Targets Poor Communication

Primary care physicians who have struggled to get a cardiovascular disease patient to adhere to a drug regimen may find a wealth of practical advice in an online educational program aimed at improving physician/patient communication.

“Even though we think we are good communicators, all of us can learn from each other and from these best practices, and hopefully do a better job” communicating about cardiovascular disease, said Dr. Richard H. Carmona, chair of the advisory board for the program called Time to Talk CARDIO.

What doctors see as patient noncompliance may actually be the doctor's inability to effectively communicate, especially across cultural barriers, said Dr. Carmona, who served as U.S. Surgeon General from 2002 to 2006. He currently serves as president of the Canyon Ranch Institute, a nonprofit wellness organization based in Tucson, Ariz.

On the program's Web site, physicians answer a series of questions regarding communication with their most vexing patient. Based on their replies, the program generates a list of the top six most important skills that the individual physician needs to work on, along with a selection of video vignettes that demonstrate best practices for each specific communication skill. The videos may suggest, for example, different ways of confirming that a patient understands what is being asked of him or her.

The Web site contains a library of more than 500 short videos showing doctors with patients discussing topics related to heart health.

The program is being pilot tested locally at several sites across the United States, and a national rollout is planned for February 2010, according to a press release.

Dr. Jason Dees, a family physician in New Albany, Miss., is pilot testing the program in his practice. The patient-centered medical home is about communication among the office staff as well as between doctor and patient, noted Dr. Dees, who said that he has shared information from the program with his partners, mid-level providers, nurses, and patient educators.

The Web site provides a worksheet for patients and providers to set goals and it has been “a huge help to us,” Dr. Dees said. The program is easy for time-strapped physicians to use. “This is not a big, time-consuming training tool,” he added.

To learn more about the program, go to

www.timetotalkcardio.com

Time to Talk CARDIO is supported in part by Merck/Schering-Plough Pharmaceuticals. It was developed in partnership with the American Academy of Family Physicians, Canyon Ranch Institute, and RIASWorks, a company that supports development of medical communication tools.

—Heidi Splete

Health care providers can now make use of 13 performance measures with which to assess adult patients' risk for cardiovascular disease.

These measures, which apply to adult patients aged 18 years and older, are not guidelines, but they translate existing guidelines for CVD prevention into steps that health care providers can easily use in their offices, according to Dr. Rita Redberg, professor of medicine, University of California, San Francisco, and the chairwoman of the writing committee (Circulation 2009;120:1296-336; J. Am. Coll. Cardiol. 2009;54:1364-405).

The measures were developed by the American College of Cardiology Foundation/American Heart Association task force on Performance Measures, in collaboration with the American Academy of Family Physicians, American Association of Cardiovascular and Pulmonary Rehabilitation, and Preventive Cardiovascular Nurses Association. They were endorsed by the American College of Preventive Medicine, American College of Sports Medicine, and Society for Women's Health Research.

The task force used guidelines supported by the strongest level of evidence, “the ones we really think make a difference in terms of patient care and patient outcomes,” Dr. Redberg, director of women's cardiovascular services at UCSF Medical Center, said in an interview.

The lifestyle/risk factor screening performance measure, for example, entails an assessment of lifestyle and risk factors for development of CVD; the second measure on the list, dietary intake counseling, provides advice about maintaining a healthy diet.

The remaining 11 performance measures are as follows: physical activity counseling; smoking/tobacco use; smoking/tobacco cessation; weight/adiposity assessment; weight management; blood pressure management; blood pressure control; blood lipid measurement; blood lipid therapy and control; global risk estimation; and aspirin use. The Global Risk evaluation measure entails use of a multivariate risk score to estimate a patient's absolute risk for development of CVD.

Several appendices are included with useful references, such as a sample performance measure survey form, a sample data collection flow sheet, a table for calculating body mass index, and a guideline on how to measure waist circumference.

The task force is hopeful that the table will be a useful reference in the office. Incorporating the measures into electronic medical records would be the most practical and efficient approach, but she said the measures were designed to be accessible and user friendly for offices that use only paper records, said Dr. Redberg, who had no conflicts to disclose.

Web Site Targets Poor Communication

Primary care physicians who have struggled to get a cardiovascular disease patient to adhere to a drug regimen may find a wealth of practical advice in an online educational program aimed at improving physician/patient communication.

“Even though we think we are good communicators, all of us can learn from each other and from these best practices, and hopefully do a better job” communicating about cardiovascular disease, said Dr. Richard H. Carmona, chair of the advisory board for the program called Time to Talk CARDIO.

What doctors see as patient noncompliance may actually be the doctor's inability to effectively communicate, especially across cultural barriers, said Dr. Carmona, who served as U.S. Surgeon General from 2002 to 2006. He currently serves as president of the Canyon Ranch Institute, a nonprofit wellness organization based in Tucson, Ariz.

On the program's Web site, physicians answer a series of questions regarding communication with their most vexing patient. Based on their replies, the program generates a list of the top six most important skills that the individual physician needs to work on, along with a selection of video vignettes that demonstrate best practices for each specific communication skill. The videos may suggest, for example, different ways of confirming that a patient understands what is being asked of him or her.

The Web site contains a library of more than 500 short videos showing doctors with patients discussing topics related to heart health.

The program is being pilot tested locally at several sites across the United States, and a national rollout is planned for February 2010, according to a press release.

Dr. Jason Dees, a family physician in New Albany, Miss., is pilot testing the program in his practice. The patient-centered medical home is about communication among the office staff as well as between doctor and patient, noted Dr. Dees, who said that he has shared information from the program with his partners, mid-level providers, nurses, and patient educators.

The Web site provides a worksheet for patients and providers to set goals and it has been “a huge help to us,” Dr. Dees said. The program is easy for time-strapped physicians to use. “This is not a big, time-consuming training tool,” he added.

To learn more about the program, go to

www.timetotalkcardio.com

Time to Talk CARDIO is supported in part by Merck/Schering-Plough Pharmaceuticals. It was developed in partnership with the American Academy of Family Physicians, Canyon Ranch Institute, and RIASWorks, a company that supports development of medical communication tools.

—Heidi Splete

Health care providers can now make use of 13 performance measures with which to assess adult patients' risk for cardiovascular disease.

These measures, which apply to adult patients aged 18 years and older, are not guidelines, but they translate existing guidelines for CVD prevention into steps that health care providers can easily use in their offices, according to Dr. Rita Redberg, professor of medicine, University of California, San Francisco, and the chairwoman of the writing committee (Circulation 2009;120:1296-336; J. Am. Coll. Cardiol. 2009;54:1364-405).

The measures were developed by the American College of Cardiology Foundation/American Heart Association task force on Performance Measures, in collaboration with the American Academy of Family Physicians, American Association of Cardiovascular and Pulmonary Rehabilitation, and Preventive Cardiovascular Nurses Association. They were endorsed by the American College of Preventive Medicine, American College of Sports Medicine, and Society for Women's Health Research.

The task force used guidelines supported by the strongest level of evidence, “the ones we really think make a difference in terms of patient care and patient outcomes,” Dr. Redberg, director of women's cardiovascular services at UCSF Medical Center, said in an interview.

The lifestyle/risk factor screening performance measure, for example, entails an assessment of lifestyle and risk factors for development of CVD; the second measure on the list, dietary intake counseling, provides advice about maintaining a healthy diet.

The remaining 11 performance measures are as follows: physical activity counseling; smoking/tobacco use; smoking/tobacco cessation; weight/adiposity assessment; weight management; blood pressure management; blood pressure control; blood lipid measurement; blood lipid therapy and control; global risk estimation; and aspirin use. The Global Risk evaluation measure entails use of a multivariate risk score to estimate a patient's absolute risk for development of CVD.

Several appendices are included with useful references, such as a sample performance measure survey form, a sample data collection flow sheet, a table for calculating body mass index, and a guideline on how to measure waist circumference.

The task force is hopeful that the table will be a useful reference in the office. Incorporating the measures into electronic medical records would be the most practical and efficient approach, but she said the measures were designed to be accessible and user friendly for offices that use only paper records, said Dr. Redberg, who had no conflicts to disclose.

Web Site Targets Poor Communication

Primary care physicians who have struggled to get a cardiovascular disease patient to adhere to a drug regimen may find a wealth of practical advice in an online educational program aimed at improving physician/patient communication.

“Even though we think we are good communicators, all of us can learn from each other and from these best practices, and hopefully do a better job” communicating about cardiovascular disease, said Dr. Richard H. Carmona, chair of the advisory board for the program called Time to Talk CARDIO.

What doctors see as patient noncompliance may actually be the doctor's inability to effectively communicate, especially across cultural barriers, said Dr. Carmona, who served as U.S. Surgeon General from 2002 to 2006. He currently serves as president of the Canyon Ranch Institute, a nonprofit wellness organization based in Tucson, Ariz.

On the program's Web site, physicians answer a series of questions regarding communication with their most vexing patient. Based on their replies, the program generates a list of the top six most important skills that the individual physician needs to work on, along with a selection of video vignettes that demonstrate best practices for each specific communication skill. The videos may suggest, for example, different ways of confirming that a patient understands what is being asked of him or her.

The Web site contains a library of more than 500 short videos showing doctors with patients discussing topics related to heart health.

The program is being pilot tested locally at several sites across the United States, and a national rollout is planned for February 2010, according to a press release.

Dr. Jason Dees, a family physician in New Albany, Miss., is pilot testing the program in his practice. The patient-centered medical home is about communication among the office staff as well as between doctor and patient, noted Dr. Dees, who said that he has shared information from the program with his partners, mid-level providers, nurses, and patient educators.

The Web site provides a worksheet for patients and providers to set goals and it has been “a huge help to us,” Dr. Dees said. The program is easy for time-strapped physicians to use. “This is not a big, time-consuming training tool,” he added.

To learn more about the program, go to

www.timetotalkcardio.com

Time to Talk CARDIO is supported in part by Merck/Schering-Plough Pharmaceuticals. It was developed in partnership with the American Academy of Family Physicians, Canyon Ranch Institute, and RIASWorks, a company that supports development of medical communication tools.

—Heidi Splete

Type 2 diabetes patients have a greater likelihood of having an acute myocardial infarction if they are treated with insulin glargine than if they are treated with human neutral protamine hagedorn insulin, according to findings from a large retrospective study.

The results are hypothesis generating and should be interpreted cautiously, noted the study's lead author Dr. George G. Rhoads of the University of Medicine and Dentistry of New Jersey School of Public Health in Piscataway and his associates.

However, they do “raise the possibility that specific insulin formulations or regimens might confer different levels of risk of [acute myocardial infarction] in patients with type 2 diabetes mellitus, and that this effect might be independent of the intensity of glucose control,” the investigators wrote (Am. J. Cardiol. 2009;104:910-6 [doi:10. 1016/j.amjcard.2009.05.030]).

The investigators culled data from the Integrated Health Care Information System, a large administrative database.

All the inpatient claims analyzed were for acute myocardial infarctions (AMIs) among patients who were taking oral antidiabetic agents after initiation of either NPH, a basal insulin (5,461 patients), or insulin glargine, a newer, long-acting synthetic insulin analog (14,730 patients). Their mean age was 56 years.

In the neutral protamine hagedorn (NPH) group, significantly more patients were women and the rates of baseline comorbidities, medical claims for hypoglycemia, and medical service use for diabetes were higher, but the rates of hypertension, hyperlipidemia, and statin use were lower. The average adjusted hemoglobin A_1c was about 8% in the two groups.

During a mean 2-year follow-up period after initiating insulin treatment, the risk of an AMI was 56% greater in NPH insulin group, when compared with the insulin glargine group.

The study was sponsored by Sanofi-Aventis, the manufacturer of insulin glargine. An independent statistical analysis was conducted by a University of Medicine and Dentistry of New Jersey statistician. Dr. Rhoads has served as a consultant to Sanofi-Aventis; other authors have served as a speaker, adviser, and consultant for the company.

Type 2 diabetes patients have a greater likelihood of having an acute myocardial infarction if they are treated with insulin glargine than if they are treated with human neutral protamine hagedorn insulin, according to findings from a large retrospective study.

The results are hypothesis generating and should be interpreted cautiously, noted the study's lead author Dr. George G. Rhoads of the University of Medicine and Dentistry of New Jersey School of Public Health in Piscataway and his associates.

However, they do “raise the possibility that specific insulin formulations or regimens might confer different levels of risk of [acute myocardial infarction] in patients with type 2 diabetes mellitus, and that this effect might be independent of the intensity of glucose control,” the investigators wrote (Am. J. Cardiol. 2009;104:910-6 [doi:10. 1016/j.amjcard.2009.05.030]).

The investigators culled data from the Integrated Health Care Information System, a large administrative database.

All the inpatient claims analyzed were for acute myocardial infarctions (AMIs) among patients who were taking oral antidiabetic agents after initiation of either NPH, a basal insulin (5,461 patients), or insulin glargine, a newer, long-acting synthetic insulin analog (14,730 patients). Their mean age was 56 years.

In the neutral protamine hagedorn (NPH) group, significantly more patients were women and the rates of baseline comorbidities, medical claims for hypoglycemia, and medical service use for diabetes were higher, but the rates of hypertension, hyperlipidemia, and statin use were lower. The average adjusted hemoglobin A_1c was about 8% in the two groups.

During a mean 2-year follow-up period after initiating insulin treatment, the risk of an AMI was 56% greater in NPH insulin group, when compared with the insulin glargine group.

The study was sponsored by Sanofi-Aventis, the manufacturer of insulin glargine. An independent statistical analysis was conducted by a University of Medicine and Dentistry of New Jersey statistician. Dr. Rhoads has served as a consultant to Sanofi-Aventis; other authors have served as a speaker, adviser, and consultant for the company.

Type 2 diabetes patients have a greater likelihood of having an acute myocardial infarction if they are treated with insulin glargine than if they are treated with human neutral protamine hagedorn insulin, according to findings from a large retrospective study.

The results are hypothesis generating and should be interpreted cautiously, noted the study's lead author Dr. George G. Rhoads of the University of Medicine and Dentistry of New Jersey School of Public Health in Piscataway and his associates.

However, they do “raise the possibility that specific insulin formulations or regimens might confer different levels of risk of [acute myocardial infarction] in patients with type 2 diabetes mellitus, and that this effect might be independent of the intensity of glucose control,” the investigators wrote (Am. J. Cardiol. 2009;104:910-6 [doi:10. 1016/j.amjcard.2009.05.030]).

The investigators culled data from the Integrated Health Care Information System, a large administrative database.

All the inpatient claims analyzed were for acute myocardial infarctions (AMIs) among patients who were taking oral antidiabetic agents after initiation of either NPH, a basal insulin (5,461 patients), or insulin glargine, a newer, long-acting synthetic insulin analog (14,730 patients). Their mean age was 56 years.

In the neutral protamine hagedorn (NPH) group, significantly more patients were women and the rates of baseline comorbidities, medical claims for hypoglycemia, and medical service use for diabetes were higher, but the rates of hypertension, hyperlipidemia, and statin use were lower. The average adjusted hemoglobin A_1c was about 8% in the two groups.

During a mean 2-year follow-up period after initiating insulin treatment, the risk of an AMI was 56% greater in NPH insulin group, when compared with the insulin glargine group.

The study was sponsored by Sanofi-Aventis, the manufacturer of insulin glargine. An independent statistical analysis was conducted by a University of Medicine and Dentistry of New Jersey statistician. Dr. Rhoads has served as a consultant to Sanofi-Aventis; other authors have served as a speaker, adviser, and consultant for the company.

SILVER SPRING, MD. — The majority of a federal advisory panel agreed that the data on a recombinant bivalent human papillomavirus vaccine indicate that the vaccine is safe and effective in preventing cervical cancer and certain precancerous or dysplastic lesions caused by HPV types 16 and 18 in girls and women aged 10-25 years.

The FDA's Vaccines and Related Biological Products Advisory Committee, voted 12-1 that the data on the GlaxoSmithKline Biologicals human papillomavirus bivalent (types 16 and 18) vaccine, recombinant, supported the efficacy of the vaccine for preventing HPV 16/18–related cervical cancer, cervical intraepithelial neoplasia (CIN) 2+, adenocarcinoma in situ (AIS), and CIN1+ in girls and women aged 15-25 years.

In a separate vote, the panel again voted 12-1 that the results of an immunogenicity bridging study from the United Kingdom, which compared immune responses to the vaccine in recipients aged 10-14 years with those of older recipients, supported effectiveness of this same claim in girls aged 10-14 years. There were no efficacy data in the younger age group, but immune responses for HPV 16/18 in the younger girls were similar to those in the older group. If approved, GSK plans to market the vaccine as Cervarix. GSK has proposed that Cervarix be licensed for prevention of cervical cancer (squamous cell cancer and adenocarcinoma, and protection against precancerous or dysplastic lesions and persistent/incident infections), caused by HPV types 16 and 18, in girls and women aged 10-25 years. It is administered in a three-dose schedule at 0, 1, and 6 months.

The majority of the panel also voted that the data supported the safety of the vaccine in girls and women aged 10-25 years but recommended that safety issues, which included spontaneous abortions, be studied further after licensure. In the pivotal study, there was a higher number of spontaneous abortions around the time of vaccination than in the comparison group.

GSK already has a Cervarix pregnancy registry in the United Kingdom and has announced plans to combine that with a registry in the United States pending FDA approval. The company has also announced plans to conduct a postmarketing safety study.

There were more musculoskeletal and neuroinflammatory events with potential autoimmune causes—although rare—among almost 30,000 Cervarix recipients, compared with controls. The three most common adverse events associated with the vaccine were headache, injection site pain, and fever.

The FDA usually follows the recommendations of its advisory panels. HPV 16 and 18 cause most cervical cancers in the United States. The vaccine was approved in May 2007, in Australia and is now licensed in 98 countries.

In the pivotal phase III, randomized, double-blind international study, more than 18,000 girls and women aged 15-25 in the general population received Cervarix or the active control, Havrix, an inactivated hepatitis A vaccine.

Over a mean follow-up of 39 months after the first dose, the vaccine was 93% effective against HPV 16/18 CIN2+ in seronegative subjects. There also was evidence that vaccination was effective in preventing this end point in women who had been previously infected with HPV 16/18, according to GSK.

Merck's quadrivalent HPV vaccine, Gardasil (human papillomavirus [types 6, 11, 16, 18] quadrivalent vaccine, recombinant), is approved for girls and women aged 9-26 years, for preventing cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 as well as associated precursor lesions and genital warts caused by HPV types 6 and 11.

SILVER SPRING, MD. — The majority of a federal advisory panel agreed that the data on a recombinant bivalent human papillomavirus vaccine indicate that the vaccine is safe and effective in preventing cervical cancer and certain precancerous or dysplastic lesions caused by HPV types 16 and 18 in girls and women aged 10-25 years.

The FDA's Vaccines and Related Biological Products Advisory Committee, voted 12-1 that the data on the GlaxoSmithKline Biologicals human papillomavirus bivalent (types 16 and 18) vaccine, recombinant, supported the efficacy of the vaccine for preventing HPV 16/18–related cervical cancer, cervical intraepithelial neoplasia (CIN) 2+, adenocarcinoma in situ (AIS), and CIN1+ in girls and women aged 15-25 years.

In a separate vote, the panel again voted 12-1 that the results of an immunogenicity bridging study from the United Kingdom, which compared immune responses to the vaccine in recipients aged 10-14 years with those of older recipients, supported effectiveness of this same claim in girls aged 10-14 years. There were no efficacy data in the younger age group, but immune responses for HPV 16/18 in the younger girls were similar to those in the older group. If approved, GSK plans to market the vaccine as Cervarix. GSK has proposed that Cervarix be licensed for prevention of cervical cancer (squamous cell cancer and adenocarcinoma, and protection against precancerous or dysplastic lesions and persistent/incident infections), caused by HPV types 16 and 18, in girls and women aged 10-25 years. It is administered in a three-dose schedule at 0, 1, and 6 months.

The majority of the panel also voted that the data supported the safety of the vaccine in girls and women aged 10-25 years but recommended that safety issues, which included spontaneous abortions, be studied further after licensure. In the pivotal study, there was a higher number of spontaneous abortions around the time of vaccination than in the comparison group.

GSK already has a Cervarix pregnancy registry in the United Kingdom and has announced plans to combine that with a registry in the United States pending FDA approval. The company has also announced plans to conduct a postmarketing safety study.

There were more musculoskeletal and neuroinflammatory events with potential autoimmune causes—although rare—among almost 30,000 Cervarix recipients, compared with controls. The three most common adverse events associated with the vaccine were headache, injection site pain, and fever.

The FDA usually follows the recommendations of its advisory panels. HPV 16 and 18 cause most cervical cancers in the United States. The vaccine was approved in May 2007, in Australia and is now licensed in 98 countries.

In the pivotal phase III, randomized, double-blind international study, more than 18,000 girls and women aged 15-25 in the general population received Cervarix or the active control, Havrix, an inactivated hepatitis A vaccine.

Over a mean follow-up of 39 months after the first dose, the vaccine was 93% effective against HPV 16/18 CIN2+ in seronegative subjects. There also was evidence that vaccination was effective in preventing this end point in women who had been previously infected with HPV 16/18, according to GSK.

Merck's quadrivalent HPV vaccine, Gardasil (human papillomavirus [types 6, 11, 16, 18] quadrivalent vaccine, recombinant), is approved for girls and women aged 9-26 years, for preventing cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 as well as associated precursor lesions and genital warts caused by HPV types 6 and 11.

SILVER SPRING, MD. — The majority of a federal advisory panel agreed that the data on a recombinant bivalent human papillomavirus vaccine indicate that the vaccine is safe and effective in preventing cervical cancer and certain precancerous or dysplastic lesions caused by HPV types 16 and 18 in girls and women aged 10-25 years.

The FDA's Vaccines and Related Biological Products Advisory Committee, voted 12-1 that the data on the GlaxoSmithKline Biologicals human papillomavirus bivalent (types 16 and 18) vaccine, recombinant, supported the efficacy of the vaccine for preventing HPV 16/18–related cervical cancer, cervical intraepithelial neoplasia (CIN) 2+, adenocarcinoma in situ (AIS), and CIN1+ in girls and women aged 15-25 years.

In a separate vote, the panel again voted 12-1 that the results of an immunogenicity bridging study from the United Kingdom, which compared immune responses to the vaccine in recipients aged 10-14 years with those of older recipients, supported effectiveness of this same claim in girls aged 10-14 years. There were no efficacy data in the younger age group, but immune responses for HPV 16/18 in the younger girls were similar to those in the older group. If approved, GSK plans to market the vaccine as Cervarix. GSK has proposed that Cervarix be licensed for prevention of cervical cancer (squamous cell cancer and adenocarcinoma, and protection against precancerous or dysplastic lesions and persistent/incident infections), caused by HPV types 16 and 18, in girls and women aged 10-25 years. It is administered in a three-dose schedule at 0, 1, and 6 months.

The majority of the panel also voted that the data supported the safety of the vaccine in girls and women aged 10-25 years but recommended that safety issues, which included spontaneous abortions, be studied further after licensure. In the pivotal study, there was a higher number of spontaneous abortions around the time of vaccination than in the comparison group.

GSK already has a Cervarix pregnancy registry in the United Kingdom and has announced plans to combine that with a registry in the United States pending FDA approval. The company has also announced plans to conduct a postmarketing safety study.

There were more musculoskeletal and neuroinflammatory events with potential autoimmune causes—although rare—among almost 30,000 Cervarix recipients, compared with controls. The three most common adverse events associated with the vaccine were headache, injection site pain, and fever.

The FDA usually follows the recommendations of its advisory panels. HPV 16 and 18 cause most cervical cancers in the United States. The vaccine was approved in May 2007, in Australia and is now licensed in 98 countries.

In the pivotal phase III, randomized, double-blind international study, more than 18,000 girls and women aged 15-25 in the general population received Cervarix or the active control, Havrix, an inactivated hepatitis A vaccine.

Over a mean follow-up of 39 months after the first dose, the vaccine was 93% effective against HPV 16/18 CIN2+ in seronegative subjects. There also was evidence that vaccination was effective in preventing this end point in women who had been previously infected with HPV 16/18, according to GSK.

Merck's quadrivalent HPV vaccine, Gardasil (human papillomavirus [types 6, 11, 16, 18] quadrivalent vaccine, recombinant), is approved for girls and women aged 9-26 years, for preventing cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 as well as associated precursor lesions and genital warts caused by HPV types 6 and 11.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9-26 years.

The FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co. The FDA usually follows the recommendations of its advisory panels. The company expects the FDA to make a decision during the fall season, according to a Merck spokesperson.

The vaccine is licensed for use in girls and women aged 9-26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9-26 years of age, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16-26 years, who received Gardasil or placebo; 85% were heterosexual and 15% were men having sex with men. (Almost 30% of the participants were in North America.) Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer. Approximately 1,800 of the subjects in the study met the protocol, and received all three Gardasil doses and were tested at month 7. In this group, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. Most of the effect was on condylomata acuminata, the focus of the proposed indication: The vaccine was 89% effective in preventing condylomata acuminata. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

An “immunobridging” study of adolescent boys (aged 9-15 years) and boys and men aged 16-26 years, who received the three Gardasil doses, determined that the immune responses to each of the four HPV types among the younger participants were not inferior to the responses seen among those in the older group. These results “inferred” efficacy of the vaccine in 9- to 15-year-olds, according to Merck.

In the pivotal trial, adverse events reported 1-15 days after any of the vaccinations, was 10% higher (74% vs. 64%) among Gardasil recipients, mostly because of injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly higher in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate.

In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA. There were no reports of syncope, which has been reported among female recipients since Gardasil was approved.

Merck is planning postlicensure studies that will continue to assess the safety and efficacy of Gardasil in males, including a 10-year follow-up of long-term safety, efficacy, and immunogenicity in the extension of the pivotal study and the immunobridging study of 9- to 15-year-olds, and a safety study using an HMO database, of about 27,000 boys and men who receive at least one dose of Gardasil.

Pamela McInnes, D.D.S., director of the division of extramural research at the National Institute of Dental and Craniofacial Research, Bethesda, Md., who voted in favor of safety and efficacy, said that duration of immunity is a “critical issue” that needs to be studied to determine whether a booster will be necessary for lifelong protection.

The consumer representative on the panel, Vicky Debold, Ph.D., R.N., director of patient safety at the National Vaccine Information Center, Vienna, Va., voted no on the safety question, and abstained on the efficacy question. More information about safety in girls is needed “before we subject boys to this,” she said, referring to a recent review of postmarketing reports of postvaccination thromboembolic events and syncope in JAMA (2009;302:750-7).

In that study of postvaccine problems reported to the Vaccine Adverse Events Reporting System (VAERS) over a 2.4-year period, reports of syncope and venous thromboembolism after vaccination with Gardasil exceeded the expected background rates. The company responded that Gardasil has not been associated with an increase in thromboembolic events, and that the events reported have been in people with risk factors for thromboembolism.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9-26 years.

The FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co. The FDA usually follows the recommendations of its advisory panels. The company expects the FDA to make a decision during the fall season, according to a Merck spokesperson.

The vaccine is licensed for use in girls and women aged 9-26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9-26 years of age, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16-26 years, who received Gardasil or placebo; 85% were heterosexual and 15% were men having sex with men. (Almost 30% of the participants were in North America.) Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer. Approximately 1,800 of the subjects in the study met the protocol, and received all three Gardasil doses and were tested at month 7. In this group, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. Most of the effect was on condylomata acuminata, the focus of the proposed indication: The vaccine was 89% effective in preventing condylomata acuminata. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

An “immunobridging” study of adolescent boys (aged 9-15 years) and boys and men aged 16-26 years, who received the three Gardasil doses, determined that the immune responses to each of the four HPV types among the younger participants were not inferior to the responses seen among those in the older group. These results “inferred” efficacy of the vaccine in 9- to 15-year-olds, according to Merck.

In the pivotal trial, adverse events reported 1-15 days after any of the vaccinations, was 10% higher (74% vs. 64%) among Gardasil recipients, mostly because of injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly higher in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate.

In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA. There were no reports of syncope, which has been reported among female recipients since Gardasil was approved.

Merck is planning postlicensure studies that will continue to assess the safety and efficacy of Gardasil in males, including a 10-year follow-up of long-term safety, efficacy, and immunogenicity in the extension of the pivotal study and the immunobridging study of 9- to 15-year-olds, and a safety study using an HMO database, of about 27,000 boys and men who receive at least one dose of Gardasil.

Pamela McInnes, D.D.S., director of the division of extramural research at the National Institute of Dental and Craniofacial Research, Bethesda, Md., who voted in favor of safety and efficacy, said that duration of immunity is a “critical issue” that needs to be studied to determine whether a booster will be necessary for lifelong protection.

The consumer representative on the panel, Vicky Debold, Ph.D., R.N., director of patient safety at the National Vaccine Information Center, Vienna, Va., voted no on the safety question, and abstained on the efficacy question. More information about safety in girls is needed “before we subject boys to this,” she said, referring to a recent review of postmarketing reports of postvaccination thromboembolic events and syncope in JAMA (2009;302:750-7).

In that study of postvaccine problems reported to the Vaccine Adverse Events Reporting System (VAERS) over a 2.4-year period, reports of syncope and venous thromboembolism after vaccination with Gardasil exceeded the expected background rates. The company responded that Gardasil has not been associated with an increase in thromboembolic events, and that the events reported have been in people with risk factors for thromboembolism.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9-26 years.

The FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co. The FDA usually follows the recommendations of its advisory panels. The company expects the FDA to make a decision during the fall season, according to a Merck spokesperson.

The vaccine is licensed for use in girls and women aged 9-26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9-26 years of age, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16-26 years, who received Gardasil or placebo; 85% were heterosexual and 15% were men having sex with men. (Almost 30% of the participants were in North America.) Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer. Approximately 1,800 of the subjects in the study met the protocol, and received all three Gardasil doses and were tested at month 7. In this group, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. Most of the effect was on condylomata acuminata, the focus of the proposed indication: The vaccine was 89% effective in preventing condylomata acuminata. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

An “immunobridging” study of adolescent boys (aged 9-15 years) and boys and men aged 16-26 years, who received the three Gardasil doses, determined that the immune responses to each of the four HPV types among the younger participants were not inferior to the responses seen among those in the older group. These results “inferred” efficacy of the vaccine in 9- to 15-year-olds, according to Merck.

In the pivotal trial, adverse events reported 1-15 days after any of the vaccinations, was 10% higher (74% vs. 64%) among Gardasil recipients, mostly because of injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly higher in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate.

In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA. There were no reports of syncope, which has been reported among female recipients since Gardasil was approved.

Merck is planning postlicensure studies that will continue to assess the safety and efficacy of Gardasil in males, including a 10-year follow-up of long-term safety, efficacy, and immunogenicity in the extension of the pivotal study and the immunobridging study of 9- to 15-year-olds, and a safety study using an HMO database, of about 27,000 boys and men who receive at least one dose of Gardasil.

Pamela McInnes, D.D.S., director of the division of extramural research at the National Institute of Dental and Craniofacial Research, Bethesda, Md., who voted in favor of safety and efficacy, said that duration of immunity is a “critical issue” that needs to be studied to determine whether a booster will be necessary for lifelong protection.

The consumer representative on the panel, Vicky Debold, Ph.D., R.N., director of patient safety at the National Vaccine Information Center, Vienna, Va., voted no on the safety question, and abstained on the efficacy question. More information about safety in girls is needed “before we subject boys to this,” she said, referring to a recent review of postmarketing reports of postvaccination thromboembolic events and syncope in JAMA (2009;302:750-7).

In that study of postvaccine problems reported to the Vaccine Adverse Events Reporting System (VAERS) over a 2.4-year period, reports of syncope and venous thromboembolism after vaccination with Gardasil exceeded the expected background rates. The company responded that Gardasil has not been associated with an increase in thromboembolic events, and that the events reported have been in people with risk factors for thromboembolism.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9–26 years.

At the meeting, the FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically on whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co.

The FDA usually follows the recommendations of its advisory panels. A Merck spokesperson said the company expects the FDA to make a decision during the fall. The vaccine is licensed for use in girls and women aged 9–26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9–26 years, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16–26 years, who received Gardasil or placebo; 85% were hetero-sexual and 15% were men having sex with men. Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer.

In the approximately 1,800 subjects who received all three Gardasil doses and were tested at month 7, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. The vaccine was 89% effective in preventing condylomata acuminata, the focus of the proposed indication. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

A study of adolescent boys aged 9–15 years and of boys and men aged 16–26 years who received the three Gardasil doses determined that the immune responses to each of the four HPV types among the younger participants was not inferior to the responses seen among those in the older group.

In the pivotal trial, the number of adverse events reported within 1–15 days of any of the vaccinations was 10% higher (74% vs. 64%) among Gardasil recipients, mostly due to injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly more common in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate. In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9–26 years.

At the meeting, the FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically on whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co.

The FDA usually follows the recommendations of its advisory panels. A Merck spokesperson said the company expects the FDA to make a decision during the fall. The vaccine is licensed for use in girls and women aged 9–26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9–26 years, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16–26 years, who received Gardasil or placebo; 85% were hetero-sexual and 15% were men having sex with men. Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer.

In the approximately 1,800 subjects who received all three Gardasil doses and were tested at month 7, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. The vaccine was 89% effective in preventing condylomata acuminata, the focus of the proposed indication. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

A study of adolescent boys aged 9–15 years and of boys and men aged 16–26 years who received the three Gardasil doses determined that the immune responses to each of the four HPV types among the younger participants was not inferior to the responses seen among those in the older group.

In the pivotal trial, the number of adverse events reported within 1–15 days of any of the vaccinations was 10% higher (74% vs. 64%) among Gardasil recipients, mostly due to injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly more common in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate. In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA.

SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9–26 years.

At the meeting, the FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically on whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co.

The FDA usually follows the recommendations of its advisory panels. A Merck spokesperson said the company expects the FDA to make a decision during the fall. The vaccine is licensed for use in girls and women aged 9–26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.

The expanded indication proposed by Merck is for use in boys and men aged 9–26 years, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.

Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16–26 years, who received Gardasil or placebo; 85% were hetero-sexual and 15% were men having sex with men. Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.

The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer.

In the approximately 1,800 subjects who received all three Gardasil doses and were tested at month 7, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. The vaccine was 89% effective in preventing condylomata acuminata, the focus of the proposed indication. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.

A study of adolescent boys aged 9–15 years and of boys and men aged 16–26 years who received the three Gardasil doses determined that the immune responses to each of the four HPV types among the younger participants was not inferior to the responses seen among those in the older group.

In the pivotal trial, the number of adverse events reported within 1–15 days of any of the vaccinations was 10% higher (74% vs. 64%) among Gardasil recipients, mostly due to injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly more common in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate. In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA.