Elizabeth Mechcatie

ADELPHI, MD. – Advisors to the Food and Drug Administration on Dec. 9 voted 19 to 5 that the benefits of the Ortho Evra contraceptive patch outweighed its risks, although they agreed with epidemiologic evidence that use of the patch is associated with an increased risk of venous thromboembolic events.

At a joint meeting of the FDA’s Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, panelists agreed that the risk of venous thromboembolic events (VTEs) associated with the Ortho Evra patch was greater than the VTE risk associated with combination oral contraceptives (COCs) that contain 35 mcg or less of ethinyl estradiol. But those who agreed that Ortho Evra had a favorable risk-benefit profile cited the unique features that the patch provides women, since it is the only contraceptive patch available in the United States and is an alternative to having to take a daily pill, and that it was important for women to have a range of contraceptive options available.

The majority of the panel also agreed that information about the risk-benefit profile of Ortho Evra in the prescriber and patient labels should be improved, and recommended revisions to the labels to reflect the available risk-benefit data, including the results of an FDA-funded study that found the risk of VTEs was increased in Ortho Evra users.

Ortho Evra was approved in November 2001 and contains 6 mg of norelgestromin and 750 mcg of ethinyl estradiol in a patch that is worn for 3 weeks, followed by 1 patch-free week. Exposure to ethinyl estradiol with the patch is about 60% higher than a COC containing 35 mcg of ethinyl estradiol.

Postmarketing reports of thrombotic and thromboembolic events associated with Ortho Evra appeared to be higher than rates with some COCs, so the manufacturer, Janssen Research and Development LLC, conducted two epidemiologic studies using insurance claims databases. One found the risk of VTEs was about twofold higher in women on Ortho Evra, compared with those on a COC containing norgestimate and 35 mcg of ethinyl estradiol. The other study found no increased VTE risk.

Earlier this year, a boxed warning was added to the Ortho Evra label that advises clinicians to balance the higher estrogen exposure with the patch and the "possible increased risk of VTE with the patch, against the chance of pregnancy."

The FDA-funded study, reported in October 2011, using an insurance claims database found that use of Ortho Evra was associated with about a 50% increased risk of VTEs, compared with combined hormonal contraceptives.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

ADELPHI, MD. – Advisors to the Food and Drug Administration on Dec. 9 voted 19 to 5 that the benefits of the Ortho Evra contraceptive patch outweighed its risks, although they agreed with epidemiologic evidence that use of the patch is associated with an increased risk of venous thromboembolic events.

At a joint meeting of the FDA’s Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, panelists agreed that the risk of venous thromboembolic events (VTEs) associated with the Ortho Evra patch was greater than the VTE risk associated with combination oral contraceptives (COCs) that contain 35 mcg or less of ethinyl estradiol. But those who agreed that Ortho Evra had a favorable risk-benefit profile cited the unique features that the patch provides women, since it is the only contraceptive patch available in the United States and is an alternative to having to take a daily pill, and that it was important for women to have a range of contraceptive options available.

The majority of the panel also agreed that information about the risk-benefit profile of Ortho Evra in the prescriber and patient labels should be improved, and recommended revisions to the labels to reflect the available risk-benefit data, including the results of an FDA-funded study that found the risk of VTEs was increased in Ortho Evra users.

Ortho Evra was approved in November 2001 and contains 6 mg of norelgestromin and 750 mcg of ethinyl estradiol in a patch that is worn for 3 weeks, followed by 1 patch-free week. Exposure to ethinyl estradiol with the patch is about 60% higher than a COC containing 35 mcg of ethinyl estradiol.

Postmarketing reports of thrombotic and thromboembolic events associated with Ortho Evra appeared to be higher than rates with some COCs, so the manufacturer, Janssen Research and Development LLC, conducted two epidemiologic studies using insurance claims databases. One found the risk of VTEs was about twofold higher in women on Ortho Evra, compared with those on a COC containing norgestimate and 35 mcg of ethinyl estradiol. The other study found no increased VTE risk.

Earlier this year, a boxed warning was added to the Ortho Evra label that advises clinicians to balance the higher estrogen exposure with the patch and the "possible increased risk of VTE with the patch, against the chance of pregnancy."

The FDA-funded study, reported in October 2011, using an insurance claims database found that use of Ortho Evra was associated with about a 50% increased risk of VTEs, compared with combined hormonal contraceptives.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

ADELPHI, MD. – Advisors to the Food and Drug Administration on Dec. 9 voted 19 to 5 that the benefits of the Ortho Evra contraceptive patch outweighed its risks, although they agreed with epidemiologic evidence that use of the patch is associated with an increased risk of venous thromboembolic events.

At a joint meeting of the FDA’s Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, panelists agreed that the risk of venous thromboembolic events (VTEs) associated with the Ortho Evra patch was greater than the VTE risk associated with combination oral contraceptives (COCs) that contain 35 mcg or less of ethinyl estradiol. But those who agreed that Ortho Evra had a favorable risk-benefit profile cited the unique features that the patch provides women, since it is the only contraceptive patch available in the United States and is an alternative to having to take a daily pill, and that it was important for women to have a range of contraceptive options available.

The majority of the panel also agreed that information about the risk-benefit profile of Ortho Evra in the prescriber and patient labels should be improved, and recommended revisions to the labels to reflect the available risk-benefit data, including the results of an FDA-funded study that found the risk of VTEs was increased in Ortho Evra users.

Ortho Evra was approved in November 2001 and contains 6 mg of norelgestromin and 750 mcg of ethinyl estradiol in a patch that is worn for 3 weeks, followed by 1 patch-free week. Exposure to ethinyl estradiol with the patch is about 60% higher than a COC containing 35 mcg of ethinyl estradiol.

Postmarketing reports of thrombotic and thromboembolic events associated with Ortho Evra appeared to be higher than rates with some COCs, so the manufacturer, Janssen Research and Development LLC, conducted two epidemiologic studies using insurance claims databases. One found the risk of VTEs was about twofold higher in women on Ortho Evra, compared with those on a COC containing norgestimate and 35 mcg of ethinyl estradiol. The other study found no increased VTE risk.

Earlier this year, a boxed warning was added to the Ortho Evra label that advises clinicians to balance the higher estrogen exposure with the patch and the "possible increased risk of VTE with the patch, against the chance of pregnancy."

The FDA-funded study, reported in October 2011, using an insurance claims database found that use of Ortho Evra was associated with about a 50% increased risk of VTEs, compared with combined hormonal contraceptives.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

ADELPHI, MD. – The benefits of Yasmin and other drospirenone-containing oral contraceptives outweigh their risks, but more information about the agents’ risk-benefit profile needs to be added to the labels, according the majority of a Food and Drug Administration advisory panel.

The agency on Dec. 8 convened a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to review the conflicting results of numerous epidemiologic studies evaluating the risk of venous thromboembolic events (VTEs) associated with Yasmin, Yaz, and other combined oral contraceptives (COCs) that contain drospirenone (DRSP) as the progestin component. Panelists voted 15-11 that the benefits of these products for preventing pregnancy in the general population of women outweighed their risks and voted 21-5 that the labels for these products did not adequately reflect available information about their risk-benefit profile.

In 2001, Yasmin (0.03 mg of ethinyl estradiol with 3 mg of DRSP) was the first COC that contained DRSP, a spironolactone analogue with antimineralcorticoid activity and antiandrogenic activity, that was approved. It was followed by Yaz (0.02 mg of ethinyl estradiol with 3 mg of DRSP) in 2006, and Safyral and Beyaz, folate-containing versions of Yasmin and Yaz, respectively, which were approved in 2010. Some generic formulations are also available.

Postmarketing studies conducted by Bayer HealthCare Pharmaceuticals – the manufacturer of Yaz, Safyral, Yasmin, and Beyaz – in Europe and the United States, found no increased risk of VTEs, compared with other COCs. But other epidemiologic studies, including a recently reported FDA-funded study of more than 800,000 women, have found an increased risk of VTE associated with these products, when compared to standard low-dose COCs.

Some of the information about VTE risk has been added to the labels of these products, but panelists recommended providing more information, which would help clinicians counsel patients. Those who voted that the benefits outweighed the risks said that if the risk was elevated, it was modest, adding that it is important to have more contraceptive choices available. Those who voted that the benefits did not outweigh the risks said there were no unique benefits of DRSP-containing COCs over other available alternatives.

Relatives of several young women who had fatal pulmonary emboli while on Yaz testified during the open public hearing portion of the meeting, calling for the withdrawal of DRSP-containing contraceptives from the market, as did several women’s health advocates who also testified.

The FDA’s assessment of the available data indicates that these products, primarily Yasmin, appear to be associated with an increased VTE risk, compared with COCs that contain other progestins, an FDA official said at the meeting, But because many factors can influence risk, data need to be re-analyzed to evaluate the impact of these risk factors before "before we can conclude that Yasmin carries an increased risk of VTE," the official said, referring to Yasmin since that is the most studied of all these products.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

ADELPHI, MD. – The benefits of Yasmin and other drospirenone-containing oral contraceptives outweigh their risks, but more information about the agents’ risk-benefit profile needs to be added to the labels, according the majority of a Food and Drug Administration advisory panel.

The agency on Dec. 8 convened a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to review the conflicting results of numerous epidemiologic studies evaluating the risk of venous thromboembolic events (VTEs) associated with Yasmin, Yaz, and other combined oral contraceptives (COCs) that contain drospirenone (DRSP) as the progestin component. Panelists voted 15-11 that the benefits of these products for preventing pregnancy in the general population of women outweighed their risks and voted 21-5 that the labels for these products did not adequately reflect available information about their risk-benefit profile.

In 2001, Yasmin (0.03 mg of ethinyl estradiol with 3 mg of DRSP) was the first COC that contained DRSP, a spironolactone analogue with antimineralcorticoid activity and antiandrogenic activity, that was approved. It was followed by Yaz (0.02 mg of ethinyl estradiol with 3 mg of DRSP) in 2006, and Safyral and Beyaz, folate-containing versions of Yasmin and Yaz, respectively, which were approved in 2010. Some generic formulations are also available.

Postmarketing studies conducted by Bayer HealthCare Pharmaceuticals – the manufacturer of Yaz, Safyral, Yasmin, and Beyaz – in Europe and the United States, found no increased risk of VTEs, compared with other COCs. But other epidemiologic studies, including a recently reported FDA-funded study of more than 800,000 women, have found an increased risk of VTE associated with these products, when compared to standard low-dose COCs.

Some of the information about VTE risk has been added to the labels of these products, but panelists recommended providing more information, which would help clinicians counsel patients. Those who voted that the benefits outweighed the risks said that if the risk was elevated, it was modest, adding that it is important to have more contraceptive choices available. Those who voted that the benefits did not outweigh the risks said there were no unique benefits of DRSP-containing COCs over other available alternatives.

Relatives of several young women who had fatal pulmonary emboli while on Yaz testified during the open public hearing portion of the meeting, calling for the withdrawal of DRSP-containing contraceptives from the market, as did several women’s health advocates who also testified.

The FDA’s assessment of the available data indicates that these products, primarily Yasmin, appear to be associated with an increased VTE risk, compared with COCs that contain other progestins, an FDA official said at the meeting, But because many factors can influence risk, data need to be re-analyzed to evaluate the impact of these risk factors before "before we can conclude that Yasmin carries an increased risk of VTE," the official said, referring to Yasmin since that is the most studied of all these products.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

ADELPHI, MD. – The benefits of Yasmin and other drospirenone-containing oral contraceptives outweigh their risks, but more information about the agents’ risk-benefit profile needs to be added to the labels, according the majority of a Food and Drug Administration advisory panel.

The agency on Dec. 8 convened a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to review the conflicting results of numerous epidemiologic studies evaluating the risk of venous thromboembolic events (VTEs) associated with Yasmin, Yaz, and other combined oral contraceptives (COCs) that contain drospirenone (DRSP) as the progestin component. Panelists voted 15-11 that the benefits of these products for preventing pregnancy in the general population of women outweighed their risks and voted 21-5 that the labels for these products did not adequately reflect available information about their risk-benefit profile.

In 2001, Yasmin (0.03 mg of ethinyl estradiol with 3 mg of DRSP) was the first COC that contained DRSP, a spironolactone analogue with antimineralcorticoid activity and antiandrogenic activity, that was approved. It was followed by Yaz (0.02 mg of ethinyl estradiol with 3 mg of DRSP) in 2006, and Safyral and Beyaz, folate-containing versions of Yasmin and Yaz, respectively, which were approved in 2010. Some generic formulations are also available.

Postmarketing studies conducted by Bayer HealthCare Pharmaceuticals – the manufacturer of Yaz, Safyral, Yasmin, and Beyaz – in Europe and the United States, found no increased risk of VTEs, compared with other COCs. But other epidemiologic studies, including a recently reported FDA-funded study of more than 800,000 women, have found an increased risk of VTE associated with these products, when compared to standard low-dose COCs.

Some of the information about VTE risk has been added to the labels of these products, but panelists recommended providing more information, which would help clinicians counsel patients. Those who voted that the benefits outweighed the risks said that if the risk was elevated, it was modest, adding that it is important to have more contraceptive choices available. Those who voted that the benefits did not outweigh the risks said there were no unique benefits of DRSP-containing COCs over other available alternatives.

Relatives of several young women who had fatal pulmonary emboli while on Yaz testified during the open public hearing portion of the meeting, calling for the withdrawal of DRSP-containing contraceptives from the market, as did several women’s health advocates who also testified.

The FDA’s assessment of the available data indicates that these products, primarily Yasmin, appear to be associated with an increased VTE risk, compared with COCs that contain other progestins, an FDA official said at the meeting, But because many factors can influence risk, data need to be re-analyzed to evaluate the impact of these risk factors before "before we can conclude that Yasmin carries an increased risk of VTE," the official said, referring to Yasmin since that is the most studied of all these products.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The data on the kinase inhibitor axitinib support its approval as a second-line treatment for advanced renal cell carcinoma, a Food and Drug Administration advisory panel unanimously agreed at a Dec. 7 meeting.

At the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-0 that axitinib has a favorable risk-benefit profile for treating patients with advanced renal cell carcinoma (RCC) after failure of a first-line systemic therapy, based on the results of an international, phase III, open-label, randomized, controlled study comparing treatment with axitinib to sorafenib (Nexavar). Sorafenib was approved in December 2005 as the first targeted therapy for RCC. Both sorafenib and axitinib are selective inhibitors of vascular endothelial growth factor (VEGF) and are administered orally twice a day.

The study enrolled 723 patients with advanced RCC who had failed one prior systemic treatment; their median age was 61 years, almost two-thirds were men, and about two-thirds were white. About 25% of the patients were enrolled in North America, and about half were enrolled in Europe. The median progression-free survival was 6.7 months among those treated with axitinib, compared with 4.7 months among those treated with sorafenib, a highly statistically significant difference.

However, the efficacy findings were driven primarily by the results among patients previously treated with cytokines, a population less likely to be seen in the United States. In this subgroup, the median progression-free survival was 5.6 months, compared with 1.4 months among those previously treated with sorafenib, who are more reflective of the types of patients treated in the United States.

Common adverse events associated with axitinib included diarrhea, nausea, fatigue, asthenia, hypertension, and skin reactions. Although its safety profile is comparable to that of other VEGF inhibitors, the side effect profile is slightly different. (Hypertension and hypothyroidism were more common among those treated with axitinib, while hand-foot-and-mouth syndrome, rash, and alopecia were more likely to occur among those on sorafenib.)

Panelists agreed that the overall toxicity profile of axitinib was comparable to that of sorafenib. And although panelists described the efficacy of axitinib as only marginally or modestly better than that of sorafenib, they agreed it would be useful to have another treatment option within the same class to offer patients who had experienced adverse effects with another agent.

If approved, axitinib will be marketed as Inlyta by Pfizer, and it would be the seventh targeted treatment approved for advanced RCC. Other targeted treatments for advanced RCC approved since December 2005 are the VEGF-receptor inhibitors sunitinib (Sutent) and pazopanib (Votrient), the anti-VEGF antibody bevacizumab (Avastin), and the mammalian target of rapamycin (mTOR) inhibitors temsirolimus (Torisel) and everolimus (Afinitor).

Axinitib has not been approved elsewhere and is under review in the European Union. It is also being studied in a phase III study of patients with treatment-naive and previously treated advanced RCC, and in a phase II study of patients with hepatocellular carcinoma.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. No panelists at this meeting were given a waiver.

SILVER SPRING, MD. – The data on the kinase inhibitor axitinib support its approval as a second-line treatment for advanced renal cell carcinoma, a Food and Drug Administration advisory panel unanimously agreed at a Dec. 7 meeting.

At the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-0 that axitinib has a favorable risk-benefit profile for treating patients with advanced renal cell carcinoma (RCC) after failure of a first-line systemic therapy, based on the results of an international, phase III, open-label, randomized, controlled study comparing treatment with axitinib to sorafenib (Nexavar). Sorafenib was approved in December 2005 as the first targeted therapy for RCC. Both sorafenib and axitinib are selective inhibitors of vascular endothelial growth factor (VEGF) and are administered orally twice a day.

The study enrolled 723 patients with advanced RCC who had failed one prior systemic treatment; their median age was 61 years, almost two-thirds were men, and about two-thirds were white. About 25% of the patients were enrolled in North America, and about half were enrolled in Europe. The median progression-free survival was 6.7 months among those treated with axitinib, compared with 4.7 months among those treated with sorafenib, a highly statistically significant difference.

However, the efficacy findings were driven primarily by the results among patients previously treated with cytokines, a population less likely to be seen in the United States. In this subgroup, the median progression-free survival was 5.6 months, compared with 1.4 months among those previously treated with sorafenib, who are more reflective of the types of patients treated in the United States.

Common adverse events associated with axitinib included diarrhea, nausea, fatigue, asthenia, hypertension, and skin reactions. Although its safety profile is comparable to that of other VEGF inhibitors, the side effect profile is slightly different. (Hypertension and hypothyroidism were more common among those treated with axitinib, while hand-foot-and-mouth syndrome, rash, and alopecia were more likely to occur among those on sorafenib.)

Panelists agreed that the overall toxicity profile of axitinib was comparable to that of sorafenib. And although panelists described the efficacy of axitinib as only marginally or modestly better than that of sorafenib, they agreed it would be useful to have another treatment option within the same class to offer patients who had experienced adverse effects with another agent.

If approved, axitinib will be marketed as Inlyta by Pfizer, and it would be the seventh targeted treatment approved for advanced RCC. Other targeted treatments for advanced RCC approved since December 2005 are the VEGF-receptor inhibitors sunitinib (Sutent) and pazopanib (Votrient), the anti-VEGF antibody bevacizumab (Avastin), and the mammalian target of rapamycin (mTOR) inhibitors temsirolimus (Torisel) and everolimus (Afinitor).

Axinitib has not been approved elsewhere and is under review in the European Union. It is also being studied in a phase III study of patients with treatment-naive and previously treated advanced RCC, and in a phase II study of patients with hepatocellular carcinoma.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. No panelists at this meeting were given a waiver.

SILVER SPRING, MD. – The data on the kinase inhibitor axitinib support its approval as a second-line treatment for advanced renal cell carcinoma, a Food and Drug Administration advisory panel unanimously agreed at a Dec. 7 meeting.

At the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-0 that axitinib has a favorable risk-benefit profile for treating patients with advanced renal cell carcinoma (RCC) after failure of a first-line systemic therapy, based on the results of an international, phase III, open-label, randomized, controlled study comparing treatment with axitinib to sorafenib (Nexavar). Sorafenib was approved in December 2005 as the first targeted therapy for RCC. Both sorafenib and axitinib are selective inhibitors of vascular endothelial growth factor (VEGF) and are administered orally twice a day.

The study enrolled 723 patients with advanced RCC who had failed one prior systemic treatment; their median age was 61 years, almost two-thirds were men, and about two-thirds were white. About 25% of the patients were enrolled in North America, and about half were enrolled in Europe. The median progression-free survival was 6.7 months among those treated with axitinib, compared with 4.7 months among those treated with sorafenib, a highly statistically significant difference.

However, the efficacy findings were driven primarily by the results among patients previously treated with cytokines, a population less likely to be seen in the United States. In this subgroup, the median progression-free survival was 5.6 months, compared with 1.4 months among those previously treated with sorafenib, who are more reflective of the types of patients treated in the United States.

Common adverse events associated with axitinib included diarrhea, nausea, fatigue, asthenia, hypertension, and skin reactions. Although its safety profile is comparable to that of other VEGF inhibitors, the side effect profile is slightly different. (Hypertension and hypothyroidism were more common among those treated with axitinib, while hand-foot-and-mouth syndrome, rash, and alopecia were more likely to occur among those on sorafenib.)

Panelists agreed that the overall toxicity profile of axitinib was comparable to that of sorafenib. And although panelists described the efficacy of axitinib as only marginally or modestly better than that of sorafenib, they agreed it would be useful to have another treatment option within the same class to offer patients who had experienced adverse effects with another agent.

If approved, axitinib will be marketed as Inlyta by Pfizer, and it would be the seventh targeted treatment approved for advanced RCC. Other targeted treatments for advanced RCC approved since December 2005 are the VEGF-receptor inhibitors sunitinib (Sutent) and pazopanib (Votrient), the anti-VEGF antibody bevacizumab (Avastin), and the mammalian target of rapamycin (mTOR) inhibitors temsirolimus (Torisel) and everolimus (Afinitor).

Axinitib has not been approved elsewhere and is under review in the European Union. It is also being studied in a phase III study of patients with treatment-naive and previously treated advanced RCC, and in a phase II study of patients with hepatocellular carcinoma.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. No panelists at this meeting were given a waiver.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions.

Makena, a compounded formulation of 17-alpha hydroxyprogesterone caproate (17P), was approved by the FDA in February 2011, providing for the first time an approved version of product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.

The Nov. 8 FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified “variability” in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA “has not validated or otherwise confirmed” these results, but “has carefully reviewed the data and will conduct an onsite review of the laboratory analyses.” In addition, the FDA has begun “its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them,” a process that is ongoing, according to the statement.

“In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice,” the statement said, adding: “Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product.”

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, “in order to support access to this important drug,” the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions.

Makena, a compounded formulation of 17-alpha hydroxyprogesterone caproate (17P), was approved by the FDA in February 2011, providing for the first time an approved version of product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.

The Nov. 8 FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified “variability” in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA “has not validated or otherwise confirmed” these results, but “has carefully reviewed the data and will conduct an onsite review of the laboratory analyses.” In addition, the FDA has begun “its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them,” a process that is ongoing, according to the statement.

“In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice,” the statement said, adding: “Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product.”

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, “in order to support access to this important drug,” the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions.

Makena, a compounded formulation of 17-alpha hydroxyprogesterone caproate (17P), was approved by the FDA in February 2011, providing for the first time an approved version of product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.

The Nov. 8 FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified “variability” in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA “has not validated or otherwise confirmed” these results, but “has carefully reviewed the data and will conduct an onsite review of the laboratory analyses.” In addition, the FDA has begun “its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them,” a process that is ongoing, according to the statement.

“In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice,” the statement said, adding: “Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product.”

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, “in order to support access to this important drug,” the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

Only about 28% of the nearly 1.2 million people infected with HIV in the United States are receiving appropriate treatment and have a suppressed viral load, according to a new report released Nov. 29 by the Centers for Disease Control and Prevention.

The report’s findings signal the need for greater effort in increasing HIV testing and in keeping infected people linked to treatment, which will also have an impact on preventing transmission, Dr. Thomas R. Frieden, director of the CDC, said during a telebriefing held the same day.

Copyright Dr. A. Harrison; Dr. P. Feorino / CDC 

There are many missed opportunities for patients to be treated properly and to be counseled about prevention, Dr. Frieden said, noting that only about half of the people who are aware they have HIV remain in treatment. These gaps require "all of us to be more accountable," including health care professionals who can offer HIV testing as a regular part of medical care, as well as ongoing treatment and prevention counseling after diagnosis.

Dr. Frieden referred to the encouraging results of the recent National Institutes of Health study of heterosexual couples, which found that consistently taking antiretroviral therapy (ART) can reduce the risk of transmission to the uninfected partner by about 96%.

HIV testing is the "gateway to effective treatment and prevention," Dr. Kevin Fenton, director of the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention at the CDC, said during the briefing. But one in five people infected with HIV is unaware of his or her status, which accounts for an estimated 240,000 people in the United States, he added.*

These figures are from the Vital Signs report on "HIV Prevention Through Care and Treatment – United States," (MMWR 2011;60:1-6). The results highlight the challenges in getting patients with HIV diagnosed, into care, and controlling HIV "in themselves and their communities," Dr. Frieden pointed out.

The CDC report used different surveillance data sets and published data to provide estimates that included how many HIV-infected people in the United States receive treatment and the proportion of people with HIV who have a suppressed viral load:

• Of the estimated 1.2 million people infected with HIV in the United States in 2008, 80% had been diagnosed.

• In 2010, 9.6% of adults aged 18-64 years had been tested for HIV during the previous 12 months, ranging from 4.9% to 29.8% in different states, with higher rates in those states with a higher prevalence of HIV.

• About 77% of the people diagnosed with HIV are linked to care within 3-4 months, and 51% remained in ongoing care.

• Of the adults who were receiving care for HIV, 89% had been prescribed ART; of these people, 77% had a suppressed viral load, based on their most recent test. (A suppressed viral load is associated with reduced morbidity and mortality and a lower risk of HIV transmission to sexual partners.)

Based on these data, an estimated 28% of the 1,178,350 people infected with HIV in the United States have a suppressed viral load, according to the report.

The proportion of patients who had been prescribed ART, had achieved viral suppression, and had received prevention counseling from a health care provider during the previous year differed by age, race, and ethnicity, and reported sexual behavior. For example, 76% of those aged 18-24 years had received ART, compared with 92% of those aged 55 years and older. ART was prescribed to 92% of whites, 89% of Hispanics, and 86% of blacks, with viral suppression rates of 84%, 79%, and 70%, respectively.

A higher proportion of men who have sex with women received only a prescription for ART (91%), compared with men who have sex with men (89%) and women who have sex with men (86%). Viral suppression rates were higher among men (81% of men who have sex with men and 75% of men who have sex with women), compared with women who have sex with men (71%).

Although 77% of people were linked to care after being diagnosed with HIV infection, "more effort is needed to ensure that those patients remain in care and to eliminate disparities among subgroups who are prescribed ART and subsequently achieve viral suppression," the report concluded. The report pointed out that less than half of the patients with HIV in one of the data sets had received counseling about prevention in the previous year, especially among men who have sex with men, which indicates "a need for health-care providers to deliver HIV prevention services more consistently."

Dr. Fenton encouraged health care professionals to offer HIV testing as a regular part of medical care, as recommended by the CDC, with those at high risk being tested at least once a year. Because treatment also helps prevent transmission, health care providers should make sure that their patients with HIV infection are aware of the importance of ART and viral suppression – particularly among black gay and bisexual men – and should provide counseling about prevention, with referral to other preventive services as needed. Although many people with HIV are linked to care after they are diagnosed, they lose the connections to care for various reasons, so he encouraged health care providers to help patients get linked back to care.

In the 3 years that followed the CDC’s 2006 recommendation that HIV testing should be offered to all people aged 13-64 years, 2.8 million people were tested and 18,000 learned they were infected with HIV, Dr. Jonathan Mermin, director of the CDC’s division of HIV/AIDS Prevention, said during the briefing.

The launch of a new CDC campaign aimed at black gay and bisexual men to get tested for HIV was also announced during the briefing. The campaign includes national print and online ads, a Web site, and a Facebook page. Black gay and bisexual men are disproportionately affected by HIV, accounting for about 22% of new infections, but most do not know they are infected, according to the CDC.

*Correction, 11/30/2011: The number of U.S. patients who are unaware of their HIV status was misstated. This version has been corrected.

Only about 28% of the nearly 1.2 million people infected with HIV in the United States are receiving appropriate treatment and have a suppressed viral load, according to a new report released Nov. 29 by the Centers for Disease Control and Prevention.

The report’s findings signal the need for greater effort in increasing HIV testing and in keeping infected people linked to treatment, which will also have an impact on preventing transmission, Dr. Thomas R. Frieden, director of the CDC, said during a telebriefing held the same day.

Copyright Dr. A. Harrison; Dr. P. Feorino / CDC 

There are many missed opportunities for patients to be treated properly and to be counseled about prevention, Dr. Frieden said, noting that only about half of the people who are aware they have HIV remain in treatment. These gaps require "all of us to be more accountable," including health care professionals who can offer HIV testing as a regular part of medical care, as well as ongoing treatment and prevention counseling after diagnosis.

Dr. Frieden referred to the encouraging results of the recent National Institutes of Health study of heterosexual couples, which found that consistently taking antiretroviral therapy (ART) can reduce the risk of transmission to the uninfected partner by about 96%.

HIV testing is the "gateway to effective treatment and prevention," Dr. Kevin Fenton, director of the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention at the CDC, said during the briefing. But one in five people infected with HIV is unaware of his or her status, which accounts for an estimated 240,000 people in the United States, he added.*

These figures are from the Vital Signs report on "HIV Prevention Through Care and Treatment – United States," (MMWR 2011;60:1-6). The results highlight the challenges in getting patients with HIV diagnosed, into care, and controlling HIV "in themselves and their communities," Dr. Frieden pointed out.

The CDC report used different surveillance data sets and published data to provide estimates that included how many HIV-infected people in the United States receive treatment and the proportion of people with HIV who have a suppressed viral load:

• Of the estimated 1.2 million people infected with HIV in the United States in 2008, 80% had been diagnosed.

• In 2010, 9.6% of adults aged 18-64 years had been tested for HIV during the previous 12 months, ranging from 4.9% to 29.8% in different states, with higher rates in those states with a higher prevalence of HIV.

• About 77% of the people diagnosed with HIV are linked to care within 3-4 months, and 51% remained in ongoing care.

• Of the adults who were receiving care for HIV, 89% had been prescribed ART; of these people, 77% had a suppressed viral load, based on their most recent test. (A suppressed viral load is associated with reduced morbidity and mortality and a lower risk of HIV transmission to sexual partners.)

Based on these data, an estimated 28% of the 1,178,350 people infected with HIV in the United States have a suppressed viral load, according to the report.

The proportion of patients who had been prescribed ART, had achieved viral suppression, and had received prevention counseling from a health care provider during the previous year differed by age, race, and ethnicity, and reported sexual behavior. For example, 76% of those aged 18-24 years had received ART, compared with 92% of those aged 55 years and older. ART was prescribed to 92% of whites, 89% of Hispanics, and 86% of blacks, with viral suppression rates of 84%, 79%, and 70%, respectively.

A higher proportion of men who have sex with women received only a prescription for ART (91%), compared with men who have sex with men (89%) and women who have sex with men (86%). Viral suppression rates were higher among men (81% of men who have sex with men and 75% of men who have sex with women), compared with women who have sex with men (71%).

Although 77% of people were linked to care after being diagnosed with HIV infection, "more effort is needed to ensure that those patients remain in care and to eliminate disparities among subgroups who are prescribed ART and subsequently achieve viral suppression," the report concluded. The report pointed out that less than half of the patients with HIV in one of the data sets had received counseling about prevention in the previous year, especially among men who have sex with men, which indicates "a need for health-care providers to deliver HIV prevention services more consistently."

Dr. Fenton encouraged health care professionals to offer HIV testing as a regular part of medical care, as recommended by the CDC, with those at high risk being tested at least once a year. Because treatment also helps prevent transmission, health care providers should make sure that their patients with HIV infection are aware of the importance of ART and viral suppression – particularly among black gay and bisexual men – and should provide counseling about prevention, with referral to other preventive services as needed. Although many people with HIV are linked to care after they are diagnosed, they lose the connections to care for various reasons, so he encouraged health care providers to help patients get linked back to care.

In the 3 years that followed the CDC’s 2006 recommendation that HIV testing should be offered to all people aged 13-64 years, 2.8 million people were tested and 18,000 learned they were infected with HIV, Dr. Jonathan Mermin, director of the CDC’s division of HIV/AIDS Prevention, said during the briefing.

The launch of a new CDC campaign aimed at black gay and bisexual men to get tested for HIV was also announced during the briefing. The campaign includes national print and online ads, a Web site, and a Facebook page. Black gay and bisexual men are disproportionately affected by HIV, accounting for about 22% of new infections, but most do not know they are infected, according to the CDC.

*Correction, 11/30/2011: The number of U.S. patients who are unaware of their HIV status was misstated. This version has been corrected.

Only about 28% of the nearly 1.2 million people infected with HIV in the United States are receiving appropriate treatment and have a suppressed viral load, according to a new report released Nov. 29 by the Centers for Disease Control and Prevention.

The report’s findings signal the need for greater effort in increasing HIV testing and in keeping infected people linked to treatment, which will also have an impact on preventing transmission, Dr. Thomas R. Frieden, director of the CDC, said during a telebriefing held the same day.

Copyright Dr. A. Harrison; Dr. P. Feorino / CDC 

There are many missed opportunities for patients to be treated properly and to be counseled about prevention, Dr. Frieden said, noting that only about half of the people who are aware they have HIV remain in treatment. These gaps require "all of us to be more accountable," including health care professionals who can offer HIV testing as a regular part of medical care, as well as ongoing treatment and prevention counseling after diagnosis.

Dr. Frieden referred to the encouraging results of the recent National Institutes of Health study of heterosexual couples, which found that consistently taking antiretroviral therapy (ART) can reduce the risk of transmission to the uninfected partner by about 96%.

HIV testing is the "gateway to effective treatment and prevention," Dr. Kevin Fenton, director of the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention at the CDC, said during the briefing. But one in five people infected with HIV is unaware of his or her status, which accounts for an estimated 240,000 people in the United States, he added.*

These figures are from the Vital Signs report on "HIV Prevention Through Care and Treatment – United States," (MMWR 2011;60:1-6). The results highlight the challenges in getting patients with HIV diagnosed, into care, and controlling HIV "in themselves and their communities," Dr. Frieden pointed out.

The CDC report used different surveillance data sets and published data to provide estimates that included how many HIV-infected people in the United States receive treatment and the proportion of people with HIV who have a suppressed viral load:

• Of the estimated 1.2 million people infected with HIV in the United States in 2008, 80% had been diagnosed.

• In 2010, 9.6% of adults aged 18-64 years had been tested for HIV during the previous 12 months, ranging from 4.9% to 29.8% in different states, with higher rates in those states with a higher prevalence of HIV.

• About 77% of the people diagnosed with HIV are linked to care within 3-4 months, and 51% remained in ongoing care.

• Of the adults who were receiving care for HIV, 89% had been prescribed ART; of these people, 77% had a suppressed viral load, based on their most recent test. (A suppressed viral load is associated with reduced morbidity and mortality and a lower risk of HIV transmission to sexual partners.)

Based on these data, an estimated 28% of the 1,178,350 people infected with HIV in the United States have a suppressed viral load, according to the report.

The proportion of patients who had been prescribed ART, had achieved viral suppression, and had received prevention counseling from a health care provider during the previous year differed by age, race, and ethnicity, and reported sexual behavior. For example, 76% of those aged 18-24 years had received ART, compared with 92% of those aged 55 years and older. ART was prescribed to 92% of whites, 89% of Hispanics, and 86% of blacks, with viral suppression rates of 84%, 79%, and 70%, respectively.

A higher proportion of men who have sex with women received only a prescription for ART (91%), compared with men who have sex with men (89%) and women who have sex with men (86%). Viral suppression rates were higher among men (81% of men who have sex with men and 75% of men who have sex with women), compared with women who have sex with men (71%).

Although 77% of people were linked to care after being diagnosed with HIV infection, "more effort is needed to ensure that those patients remain in care and to eliminate disparities among subgroups who are prescribed ART and subsequently achieve viral suppression," the report concluded. The report pointed out that less than half of the patients with HIV in one of the data sets had received counseling about prevention in the previous year, especially among men who have sex with men, which indicates "a need for health-care providers to deliver HIV prevention services more consistently."

Dr. Fenton encouraged health care professionals to offer HIV testing as a regular part of medical care, as recommended by the CDC, with those at high risk being tested at least once a year. Because treatment also helps prevent transmission, health care providers should make sure that their patients with HIV infection are aware of the importance of ART and viral suppression – particularly among black gay and bisexual men – and should provide counseling about prevention, with referral to other preventive services as needed. Although many people with HIV are linked to care after they are diagnosed, they lose the connections to care for various reasons, so he encouraged health care providers to help patients get linked back to care.

In the 3 years that followed the CDC’s 2006 recommendation that HIV testing should be offered to all people aged 13-64 years, 2.8 million people were tested and 18,000 learned they were infected with HIV, Dr. Jonathan Mermin, director of the CDC’s division of HIV/AIDS Prevention, said during the briefing.

The launch of a new CDC campaign aimed at black gay and bisexual men to get tested for HIV was also announced during the briefing. The campaign includes national print and online ads, a Web site, and a Facebook page. Black gay and bisexual men are disproportionately affected by HIV, accounting for about 22% of new infections, but most do not know they are infected, according to the CDC.

*Correction, 11/30/2011: The number of U.S. patients who are unaware of their HIV status was misstated. This version has been corrected.

The approval of bevacizumab, the angiogenesis inhibitor marketed as Avastin, as a treatment for metastatic breast cancer is being withdrawn by the Food and Drug Administration, the agency announced Nov. 18.

In the statement announcing the decision, FDA commissioner Dr. Margaret Hamburg said she is revoking the approval, because the use of Avastin as a first-line treatment for metastatic breast cancer has not been shown to be safe and effective. Avastin is approved for several other types of cancers, so it will remain on the U.S. market.

The FDA granted an accelerated approval to bevacizumab in combination with paclitaxel as a first-line treatment for metastatic breast cancer in February 2008, based on an open-label study that found a survival advantage for the combined treatment, compared with treatment with paclitaxel alone. Studies confirming the beneficial effects are a condition of accelerated approvals. In this case, though, follow-up studies failed to confirm the benefit, and the FDA decided to withdraw its approval of the breast cancer indication

In an unusual move, the manufacturer, Genentech, requested a hearing on the decision, which was held in July 2011. At that meeting, the Oncologic Drugs Advisory Committee unanimously voted that approval for the breast cancer indication should be withdrawn because clinical trials did not show an improvement in overall survival or any clinically meaningful improvements in progression-free survival. The final decision was left to Dr. Hamburg.

"This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use," Dr. Hamburg said in the statement. "After reviewing the available studies, it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life." Her decision is explained in a 69-page opinion.

A statement issued by Genentech immediately after the FDA statement was released said that the company was disappointed with the outcome, remained committed to women with the disease, and would "continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment." Despite the FDA’s decision, the company said it planned to start a new phase III study of Avastin in combination with paclitaxel in women with previously untreated metastatic breast cancer, which would "evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin."

In the FDA statement, Dr. Hamburg said that she encouraged Genentech to consider other studies "to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug."

At least for now, Medicare coverage of bevacizumab will continue for women with breast cancer. A statement issued by the Centers for Medicare & Medicaid Services said that the agency would “monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.”

Avastin is still approved for treating metastatic breast cancer in more than 80 countries.

This story was updated November 18, 2011.

The approval of bevacizumab, the angiogenesis inhibitor marketed as Avastin, as a treatment for metastatic breast cancer is being withdrawn by the Food and Drug Administration, the agency announced Nov. 18.

In the statement announcing the decision, FDA commissioner Dr. Margaret Hamburg said she is revoking the approval, because the use of Avastin as a first-line treatment for metastatic breast cancer has not been shown to be safe and effective. Avastin is approved for several other types of cancers, so it will remain on the U.S. market.

The FDA granted an accelerated approval to bevacizumab in combination with paclitaxel as a first-line treatment for metastatic breast cancer in February 2008, based on an open-label study that found a survival advantage for the combined treatment, compared with treatment with paclitaxel alone. Studies confirming the beneficial effects are a condition of accelerated approvals. In this case, though, follow-up studies failed to confirm the benefit, and the FDA decided to withdraw its approval of the breast cancer indication

In an unusual move, the manufacturer, Genentech, requested a hearing on the decision, which was held in July 2011. At that meeting, the Oncologic Drugs Advisory Committee unanimously voted that approval for the breast cancer indication should be withdrawn because clinical trials did not show an improvement in overall survival or any clinically meaningful improvements in progression-free survival. The final decision was left to Dr. Hamburg.

"This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use," Dr. Hamburg said in the statement. "After reviewing the available studies, it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life." Her decision is explained in a 69-page opinion.

A statement issued by Genentech immediately after the FDA statement was released said that the company was disappointed with the outcome, remained committed to women with the disease, and would "continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment." Despite the FDA’s decision, the company said it planned to start a new phase III study of Avastin in combination with paclitaxel in women with previously untreated metastatic breast cancer, which would "evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin."

In the FDA statement, Dr. Hamburg said that she encouraged Genentech to consider other studies "to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug."

At least for now, Medicare coverage of bevacizumab will continue for women with breast cancer. A statement issued by the Centers for Medicare & Medicaid Services said that the agency would “monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.”

Avastin is still approved for treating metastatic breast cancer in more than 80 countries.

This story was updated November 18, 2011.

The approval of bevacizumab, the angiogenesis inhibitor marketed as Avastin, as a treatment for metastatic breast cancer is being withdrawn by the Food and Drug Administration, the agency announced Nov. 18.

In the statement announcing the decision, FDA commissioner Dr. Margaret Hamburg said she is revoking the approval, because the use of Avastin as a first-line treatment for metastatic breast cancer has not been shown to be safe and effective. Avastin is approved for several other types of cancers, so it will remain on the U.S. market.

The FDA granted an accelerated approval to bevacizumab in combination with paclitaxel as a first-line treatment for metastatic breast cancer in February 2008, based on an open-label study that found a survival advantage for the combined treatment, compared with treatment with paclitaxel alone. Studies confirming the beneficial effects are a condition of accelerated approvals. In this case, though, follow-up studies failed to confirm the benefit, and the FDA decided to withdraw its approval of the breast cancer indication

In an unusual move, the manufacturer, Genentech, requested a hearing on the decision, which was held in July 2011. At that meeting, the Oncologic Drugs Advisory Committee unanimously voted that approval for the breast cancer indication should be withdrawn because clinical trials did not show an improvement in overall survival or any clinically meaningful improvements in progression-free survival. The final decision was left to Dr. Hamburg.

"This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use," Dr. Hamburg said in the statement. "After reviewing the available studies, it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life." Her decision is explained in a 69-page opinion.

A statement issued by Genentech immediately after the FDA statement was released said that the company was disappointed with the outcome, remained committed to women with the disease, and would "continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment." Despite the FDA’s decision, the company said it planned to start a new phase III study of Avastin in combination with paclitaxel in women with previously untreated metastatic breast cancer, which would "evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin."

In the FDA statement, Dr. Hamburg said that she encouraged Genentech to consider other studies "to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug."

At least for now, Medicare coverage of bevacizumab will continue for women with breast cancer. A statement issued by the Centers for Medicare & Medicaid Services said that the agency would “monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.”

Avastin is still approved for treating metastatic breast cancer in more than 80 countries.

This story was updated November 18, 2011.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Nov. 16 supported expanding the approval of the pneumococcal 13-valent conjugate vaccine approved in 2010 for infants and children for use in adults aged 50 and older, based on studies using surrogate end points of effectiveness.

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 14 to 1 that the immunogenicity data on the vaccine, marketed as Prevnar 13 by Wyeth Pharmaceuticals Inc., supported its effectiveness in preventing pneumococcal disease caused by the serotypes contained in the vaccine in people aged 50 and older. The panel also voted 14 to 1 that the available data supported its safety in this older age group, with the panel’s consumer representative casting the no vote on both questions.

Prevnar 13 is under FDA review as an accelerated approval, which applies to products that "provide meaningful clinical benefit" over existing treatments for serious and life-threatening illnesses, which in the case of this vaccine is the protection of adults and the elderly from nonbacteremic pneumococcal pneumonia and protection from invasive pneumococcal disease, according to the FDA. A product can be approved under the accelerated approval regulation based on studies using surrogate effectiveness end points, if a follow-up clinical study confirming the benefits is conducted. If that study is negative, the FDA can withdraw approval.

The proposed adult indication for Prevnar 13 is for the prevention of pneumococcal disease (including pneumonia and invasive disease) caused by the Streptococcus pneumoniae serotypes contained in the vaccine, in adults aged 50 years and older. Prevnar 13 was recently approved for this indication in 29 countries in Europe and 8 other countries.

The vaccine was approved in 2010 for preventing invasive disease caused by the S. pneumoniae serotypes in the vaccine in children aged 6 weeks through 5 years; it is also approved for preventing otitis media caused by seven serotypes.

The adult formulation is identical to the pediatric vaccine.

In the two pivotal trials, immune responses with a single dose of Prevnar 13 were considered noninferior to the responses seen with a single dose of Pneumovax 23, a 23-valent polysaccharide vaccine approved in 1983 for immunizing adults aged 50 and older and children aged 2 years and older, who are at an increased risk for pneumococcal disease. With one exception, Pneumovax 23 contains the serotypes included in Prevnar 13 plus 11 others; it is the only adult pneumococcal vaccine approved in the United States. One study was conducted in the United States and compared Prevnar13 to Pneumovax 23. The study comprised 1,235 adults aged 50-64 years, who had not received a pneumococcal vaccine before; the other compared the two vaccines in 936 patients, aged 70 years and older, in the United States and Sweden. Those participants received Pneumovax 23 at least 5 years earlier.

For most serotypes in the vaccine, the immune responses were significantly higher with Prevnar 13 than with Pneumovax 23 among those aged 50-65 who had not received the pneumococcal vaccine previously and among those aged 70 years and older who had been previously vaccinated, according to Pfizer presentations at the meeting. (Wyeth is a wholly owned subsidiary of Pfizer Inc.)

There were no imbalances in deaths or serious adverse events among those who received Prevnar 13 and among those who received the older vaccine, but the safety database was not large enough to identify rare side effects, according to the FDA.

To confirm the results of these studies, Wyeth is conducting a placebo-controlled study of more than 85,000 adults aged 65 years and older in the Netherlands, evaluating the efficacy of the vaccine in preventing the first episode of pneumococcal pneumonia, which is underway."

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Nov. 16 supported expanding the approval of the pneumococcal 13-valent conjugate vaccine approved in 2010 for infants and children for use in adults aged 50 and older, based on studies using surrogate end points of effectiveness.

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 14 to 1 that the immunogenicity data on the vaccine, marketed as Prevnar 13 by Wyeth Pharmaceuticals Inc., supported its effectiveness in preventing pneumococcal disease caused by the serotypes contained in the vaccine in people aged 50 and older. The panel also voted 14 to 1 that the available data supported its safety in this older age group, with the panel’s consumer representative casting the no vote on both questions.

Prevnar 13 is under FDA review as an accelerated approval, which applies to products that "provide meaningful clinical benefit" over existing treatments for serious and life-threatening illnesses, which in the case of this vaccine is the protection of adults and the elderly from nonbacteremic pneumococcal pneumonia and protection from invasive pneumococcal disease, according to the FDA. A product can be approved under the accelerated approval regulation based on studies using surrogate effectiveness end points, if a follow-up clinical study confirming the benefits is conducted. If that study is negative, the FDA can withdraw approval.

The proposed adult indication for Prevnar 13 is for the prevention of pneumococcal disease (including pneumonia and invasive disease) caused by the Streptococcus pneumoniae serotypes contained in the vaccine, in adults aged 50 years and older. Prevnar 13 was recently approved for this indication in 29 countries in Europe and 8 other countries.

The vaccine was approved in 2010 for preventing invasive disease caused by the S. pneumoniae serotypes in the vaccine in children aged 6 weeks through 5 years; it is also approved for preventing otitis media caused by seven serotypes.

The adult formulation is identical to the pediatric vaccine.

In the two pivotal trials, immune responses with a single dose of Prevnar 13 were considered noninferior to the responses seen with a single dose of Pneumovax 23, a 23-valent polysaccharide vaccine approved in 1983 for immunizing adults aged 50 and older and children aged 2 years and older, who are at an increased risk for pneumococcal disease. With one exception, Pneumovax 23 contains the serotypes included in Prevnar 13 plus 11 others; it is the only adult pneumococcal vaccine approved in the United States. One study was conducted in the United States and compared Prevnar13 to Pneumovax 23. The study comprised 1,235 adults aged 50-64 years, who had not received a pneumococcal vaccine before; the other compared the two vaccines in 936 patients, aged 70 years and older, in the United States and Sweden. Those participants received Pneumovax 23 at least 5 years earlier.

For most serotypes in the vaccine, the immune responses were significantly higher with Prevnar 13 than with Pneumovax 23 among those aged 50-65 who had not received the pneumococcal vaccine previously and among those aged 70 years and older who had been previously vaccinated, according to Pfizer presentations at the meeting. (Wyeth is a wholly owned subsidiary of Pfizer Inc.)

There were no imbalances in deaths or serious adverse events among those who received Prevnar 13 and among those who received the older vaccine, but the safety database was not large enough to identify rare side effects, according to the FDA.

To confirm the results of these studies, Wyeth is conducting a placebo-controlled study of more than 85,000 adults aged 65 years and older in the Netherlands, evaluating the efficacy of the vaccine in preventing the first episode of pneumococcal pneumonia, which is underway."

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Nov. 16 supported expanding the approval of the pneumococcal 13-valent conjugate vaccine approved in 2010 for infants and children for use in adults aged 50 and older, based on studies using surrogate end points of effectiveness.

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 14 to 1 that the immunogenicity data on the vaccine, marketed as Prevnar 13 by Wyeth Pharmaceuticals Inc., supported its effectiveness in preventing pneumococcal disease caused by the serotypes contained in the vaccine in people aged 50 and older. The panel also voted 14 to 1 that the available data supported its safety in this older age group, with the panel’s consumer representative casting the no vote on both questions.

Prevnar 13 is under FDA review as an accelerated approval, which applies to products that "provide meaningful clinical benefit" over existing treatments for serious and life-threatening illnesses, which in the case of this vaccine is the protection of adults and the elderly from nonbacteremic pneumococcal pneumonia and protection from invasive pneumococcal disease, according to the FDA. A product can be approved under the accelerated approval regulation based on studies using surrogate effectiveness end points, if a follow-up clinical study confirming the benefits is conducted. If that study is negative, the FDA can withdraw approval.

The proposed adult indication for Prevnar 13 is for the prevention of pneumococcal disease (including pneumonia and invasive disease) caused by the Streptococcus pneumoniae serotypes contained in the vaccine, in adults aged 50 years and older. Prevnar 13 was recently approved for this indication in 29 countries in Europe and 8 other countries.

The vaccine was approved in 2010 for preventing invasive disease caused by the S. pneumoniae serotypes in the vaccine in children aged 6 weeks through 5 years; it is also approved for preventing otitis media caused by seven serotypes.

The adult formulation is identical to the pediatric vaccine.

In the two pivotal trials, immune responses with a single dose of Prevnar 13 were considered noninferior to the responses seen with a single dose of Pneumovax 23, a 23-valent polysaccharide vaccine approved in 1983 for immunizing adults aged 50 and older and children aged 2 years and older, who are at an increased risk for pneumococcal disease. With one exception, Pneumovax 23 contains the serotypes included in Prevnar 13 plus 11 others; it is the only adult pneumococcal vaccine approved in the United States. One study was conducted in the United States and compared Prevnar13 to Pneumovax 23. The study comprised 1,235 adults aged 50-64 years, who had not received a pneumococcal vaccine before; the other compared the two vaccines in 936 patients, aged 70 years and older, in the United States and Sweden. Those participants received Pneumovax 23 at least 5 years earlier.

For most serotypes in the vaccine, the immune responses were significantly higher with Prevnar 13 than with Pneumovax 23 among those aged 50-65 who had not received the pneumococcal vaccine previously and among those aged 70 years and older who had been previously vaccinated, according to Pfizer presentations at the meeting. (Wyeth is a wholly owned subsidiary of Pfizer Inc.)

There were no imbalances in deaths or serious adverse events among those who received Prevnar 13 and among those who received the older vaccine, but the safety database was not large enough to identify rare side effects, according to the FDA.

To confirm the results of these studies, Wyeth is conducting a placebo-controlled study of more than 85,000 adults aged 65 years and older in the Netherlands, evaluating the efficacy of the vaccine in preventing the first episode of pneumococcal pneumonia, which is underway."

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions. The agency announced this on Nov. 8.

Makena, a prescription hormone medicine (progestin), was approved by the FDA in February 2011, providing for the first time an approved version of a product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.*

The FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified "variability" in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA "has not validated or otherwise confirmed" these results, but "has carefully reviewed the data and will conduct an onsite review of the laboratory analyses." In addition, the FDA has begun "its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them," a process that is ongoing, according to the statement.

"In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice," the statement said, adding: "Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product."

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, "in order to support access to this important drug," the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

*Correction, 12/20/2011: An earlier version of this story mischaracterized Makena.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions. The agency announced this on Nov. 8.

Makena, a prescription hormone medicine (progestin), was approved by the FDA in February 2011, providing for the first time an approved version of a product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.*

The FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified "variability" in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA "has not validated or otherwise confirmed" these results, but "has carefully reviewed the data and will conduct an onsite review of the laboratory analyses." In addition, the FDA has begun "its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them," a process that is ongoing, according to the statement.

"In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice," the statement said, adding: "Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product."

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, "in order to support access to this important drug," the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

*Correction, 12/20/2011: An earlier version of this story mischaracterized Makena.

The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions. The agency announced this on Nov. 8.

Makena, a prescription hormone medicine (progestin), was approved by the FDA in February 2011, providing for the first time an approved version of a product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.*

The FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified "variability" in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA "has not validated or otherwise confirmed" these results, but "has carefully reviewed the data and will conduct an onsite review of the laboratory analyses." In addition, the FDA has begun "its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them," a process that is ongoing, according to the statement.

"In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice," the statement said, adding: "Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product."

Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.

Despite the availability of an approved product, the FDA released a statement in March that said, "in order to support access to this important drug," the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.

*Correction, 12/20/2011: An earlier version of this story mischaracterized Makena.