Joseph Haas

The key to Genzyme Corp.’s move to withdraw its leukemia drug, Campath, in anticipation of a multiple sclerosis indication seems to be working with the cancer community and establishing generous patient support.

Genzyme, the rare disease unit of Sanofi, is in the process of removing the Campath brand of alemtuzumab from commercial availability in about 50 markets, including the United States and the European Union – and the company has been transparent about its reasoning. It does not want Campath to be used off label in the multiple sclerosis setting when a lower-dose formulation of alemtuzumab obtains approval for multiple sclerosis.

But instead of courting controversy with the potentially contentious business decision, the firm has decided to make Campath available free of charge under a patient-access program. The leukemia treatment had reportedly cost in the range of $50,000-$60,000.

In an Aug. 9 letter to health care providers, Genzyme makes clear that it will stop selling Campath, not "for any reasons related to product safety, efficacy or supply, but as part of the company’s plan for bringing alemtuzumab forward as a treatment for a new indication." The company added that it "will continue manufacturing sufficient quantities of alemtuzumab to supply this patient access program."

Although sacrificing one patient community (and cancer, at that) in favor of a more lucrative one certainly seems as if it could provoke controversy, the steps Genzyme took appear to be enough to ease the company past public outcry.

Hildy Dillon, senior vice president of patient services for the Leukemia and Lymphoma Society, said that her organization was concerned when it first learned of Sanofi/Genzyme’s plans to stop selling Campath, but added that the companies had done a strong job of laying the groundwork for a transition from commercial product to one available for free under a compassionate-use protocol.

"There is an extensive patient-distribution system which they have shared with us," she said in an interview. "They’ve actually been quite supportive to us and our constituents by telling us what the distribution is and how they have communicated their plans to health care providers who treat our patients – hematology oncologists both in the community and in the major cancer centers.

"[Those doctors] are now aware of how they can access the drug since they no longer will be purchasing it, but they can contact the company directly to get whatever supply they need."

Campath Available to New Patients

Ms. Dillon said the Leukemia and Lymphoma Society was assured that Campath will be available for all patients who need it, including those who may be prescribed it for the first time after it is no longer available commercially.

"Genzyme was in touch with advocacy groups like ours to make sure we were aware of the change and how physicians will be accessing the drug," she said. "They’ve done a lot in their due diligence to inform both the physician community and the patients. ... It’s our understanding that there won’t be any shortage of supply and that the patients who need Campath will be able to get it."

By making it harder for alemtuzumab to be used in the MS setting off label, Genzyme also increases its chances of making the product (to be marketed as Lemtrada in the MS indication) much more lucrative. Campath, an anti-CD52 monoclonal antibody indicated for the treatment of chronic lymphocytic leukemia (CLL), yielded net sales of $76 million last year for Sanofi. The French pharmaceutical company bought out Genzyme for about $19.4 billion in early 2011, largely on the strength of the biotech company’s success in developing large-molecule products for rare disorders.

Industry analysts predict much bigger sales for Lemtrada, which will be provided in a 12-mg dose per treatment, compared with 30 mg for Campath. A supplemental Biologics License Application was filed at the Food and Drug Administration this past June, with a marketing authorization application sent to the European Medicines Agency in the same time frame, which means that regulatory decisions on Lemtrada are anticipated during the second quarter of 2013. Analysts widely predict initial-review approvals by the FDA and the EMA, a launch in late 2013, and the ramp-up to sales ranging between $336 million and $400 million in 2016.

No Similarity to Genentech AMD Dilemma, Genzyme Says

Sanofi/Genzyme’s dilemma regarding what to do with a useful but modestly selling drug that offers the potential to earn more in a second indication mirrors in some ways the challenge faced by Roche/Genentech Inc. with its vascular endothelial growth factor therapies Lucentis (ranibizumab) and Avastin (becavizumab). Both demonstrated potential in clinical trials for the treatment of wet age-related macular degeneration, but Roche never filed Avastin for AMD because it would undercut the Lucentis market in that indication. Lucentis costs about $2,000 per injection, while oncology drug Avastin is available in small-dose syringes for between $35 and $50 per unit.

A Genzyme spokesperson denied the similarity between the two business cases, however. "We believe the situation that we are managing with alemtuzumab is unique," he said in an e-mail exchange.

Sanofi/Genzyme made its decision on withdrawing Campath gradually, and consulted the MS and oncology communities, including patient advocacy groups, along the way, the spokesperson added.

"We are changing the way Campath is made available for its current use because we have decided to focus on bringing alemtuzumab forward for MS, where it holds the potential to address a significant unmet need," he said. "Importantly, this step will also help ensure that the product is used for MS patients only within the clinical trial setting prior to approval, given the differences in dosing and safety profile associated with its use in CLL and MS."

Because Lemtrada is a lower dosage of alemtuzumab than is Campath, it has a different safety profile. The MS space offers multiple therapeutic options, but each – including Lemtrada, if approved – poses potential safety issues.

Biogen Idec Inc. and Elan Corp. continually have battled reports of progressive multifocal leukoencephalopathy (PML) in patients treated with their drug, Tysabri (natalizumab), which claimed 12% of the MS market in 2011, garnering sales of $1.5 billion. Sales have picked up in recent months now that patients can use a diagnostic to predict their risk for PML.

Novartis AG markets a once-daily oral drug for MS, Gilenya (fingolimod), which launched in 2011, claiming a 4% share of the market and sales of $494 million. That product, however, sometimes presents cardiovascular side effects.

In a pivotal trial testing alemtuzumab in relapsed, remitting MS, Sanofi/Genzyme found that 15.9% of treatment-arm patients experienced autoimmune-related thyroid adverse events, compared with just 5% of control-arm patients who received Roche’s Rebif (interferon beta-1a). Meanwhile, 0.9% of the alemtuzumab recipients developed immune thrombocytopenia over a 2-year treatment period.

Genzyme, which has a management program in place to detect and treat both types of adverse events, says that even higher rates of autoimmune effects have been seen in MS testing with the antibody, but more than 90% of such cases are mild to moderate in severity and are treatable with standard therapies. At the 30-mg dosage used for CLL, the Campath label includes warnings for risk of cytopenia, infections, and infusion reactions.

Dosing, Efficacy Advantages Expected in MS

Dosing and efficacy both are expected to give Lemtrada a potential leg up in the MS space. Lemtrada would be dosed much less frequently than other MS drugs, although it would not offer the convenience of oral availability presented by Gilenya. An intravenous infusion drug, Lemtrada would be dosed at 12 mg for 5 consecutive days during the first year of treatment and then for 3 consecutive days the following year.

In the CARE-MS II trial, alemtuzumab reversed disability in nearly one-third of patients whose disease had relapsed while they received other therapy. Top-line data showed a 49% reduction in relapse rate, compared with patients treated with Rebif, along with a 42% reduction in worsening of disability. Longer-term data from the trial showed a reduction in disability, as measured by the Expanded Disability Status Scale, for treatment-arm patients, whereas control-arm patients saw increased disability.

In December 2010, while the Sanofi acquisition of Genzyme was being negotiated, Genzyme offered projections that Lemtrada would achieve 5% market share in its launch year, moving up to 10% and 12% in years 2 and 3 on the market, and an 18%-20% share by year 5. At that time, then–Genzyme executive Mark Enyedy acknowledged concerns "about managing the use of the oncology product in MS" and talked of a range of solutions, which included pulling Campath from commercialization.

Perhaps the most bullish on Lemtrada’s market potential is Stephen McGarry, an analyst with Société Générale Cross Asset Research. He projects Lemtrada’s reaching 472 million euros in sales by 2016 and continuing to grow, peaking at 1.134 billion euros in 2020. "Although we view the side effect profile as a negative relative to competing drugs in the MS space, and its route of administration is not oral, which is also a potential disadvantage, the dosing frequency and high level of efficacy more than balance those concerns in our view," he wrote in an Aug. 9 note.

Sanofi has another MS candidate, Aubagio (teriflunomide), pending at the FDA with a Sept. 12 action date. It plans to position Aubagio, an oral pill, as a convenient therapy for patients in early stages of MS, whereas Lemtrada would be targeted to those with more serious, later-stage disease.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

The key to Genzyme Corp.’s move to withdraw its leukemia drug, Campath, in anticipation of a multiple sclerosis indication seems to be working with the cancer community and establishing generous patient support.

Genzyme, the rare disease unit of Sanofi, is in the process of removing the Campath brand of alemtuzumab from commercial availability in about 50 markets, including the United States and the European Union – and the company has been transparent about its reasoning. It does not want Campath to be used off label in the multiple sclerosis setting when a lower-dose formulation of alemtuzumab obtains approval for multiple sclerosis.

But instead of courting controversy with the potentially contentious business decision, the firm has decided to make Campath available free of charge under a patient-access program. The leukemia treatment had reportedly cost in the range of $50,000-$60,000.

In an Aug. 9 letter to health care providers, Genzyme makes clear that it will stop selling Campath, not "for any reasons related to product safety, efficacy or supply, but as part of the company’s plan for bringing alemtuzumab forward as a treatment for a new indication." The company added that it "will continue manufacturing sufficient quantities of alemtuzumab to supply this patient access program."

Although sacrificing one patient community (and cancer, at that) in favor of a more lucrative one certainly seems as if it could provoke controversy, the steps Genzyme took appear to be enough to ease the company past public outcry.

Hildy Dillon, senior vice president of patient services for the Leukemia and Lymphoma Society, said that her organization was concerned when it first learned of Sanofi/Genzyme’s plans to stop selling Campath, but added that the companies had done a strong job of laying the groundwork for a transition from commercial product to one available for free under a compassionate-use protocol.

"There is an extensive patient-distribution system which they have shared with us," she said in an interview. "They’ve actually been quite supportive to us and our constituents by telling us what the distribution is and how they have communicated their plans to health care providers who treat our patients – hematology oncologists both in the community and in the major cancer centers.

"[Those doctors] are now aware of how they can access the drug since they no longer will be purchasing it, but they can contact the company directly to get whatever supply they need."

Campath Available to New Patients

Ms. Dillon said the Leukemia and Lymphoma Society was assured that Campath will be available for all patients who need it, including those who may be prescribed it for the first time after it is no longer available commercially.

"Genzyme was in touch with advocacy groups like ours to make sure we were aware of the change and how physicians will be accessing the drug," she said. "They’ve done a lot in their due diligence to inform both the physician community and the patients. ... It’s our understanding that there won’t be any shortage of supply and that the patients who need Campath will be able to get it."

By making it harder for alemtuzumab to be used in the MS setting off label, Genzyme also increases its chances of making the product (to be marketed as Lemtrada in the MS indication) much more lucrative. Campath, an anti-CD52 monoclonal antibody indicated for the treatment of chronic lymphocytic leukemia (CLL), yielded net sales of $76 million last year for Sanofi. The French pharmaceutical company bought out Genzyme for about $19.4 billion in early 2011, largely on the strength of the biotech company’s success in developing large-molecule products for rare disorders.

Industry analysts predict much bigger sales for Lemtrada, which will be provided in a 12-mg dose per treatment, compared with 30 mg for Campath. A supplemental Biologics License Application was filed at the Food and Drug Administration this past June, with a marketing authorization application sent to the European Medicines Agency in the same time frame, which means that regulatory decisions on Lemtrada are anticipated during the second quarter of 2013. Analysts widely predict initial-review approvals by the FDA and the EMA, a launch in late 2013, and the ramp-up to sales ranging between $336 million and $400 million in 2016.

No Similarity to Genentech AMD Dilemma, Genzyme Says

Sanofi/Genzyme’s dilemma regarding what to do with a useful but modestly selling drug that offers the potential to earn more in a second indication mirrors in some ways the challenge faced by Roche/Genentech Inc. with its vascular endothelial growth factor therapies Lucentis (ranibizumab) and Avastin (becavizumab). Both demonstrated potential in clinical trials for the treatment of wet age-related macular degeneration, but Roche never filed Avastin for AMD because it would undercut the Lucentis market in that indication. Lucentis costs about $2,000 per injection, while oncology drug Avastin is available in small-dose syringes for between $35 and $50 per unit.

A Genzyme spokesperson denied the similarity between the two business cases, however. "We believe the situation that we are managing with alemtuzumab is unique," he said in an e-mail exchange.

Sanofi/Genzyme made its decision on withdrawing Campath gradually, and consulted the MS and oncology communities, including patient advocacy groups, along the way, the spokesperson added.

"We are changing the way Campath is made available for its current use because we have decided to focus on bringing alemtuzumab forward for MS, where it holds the potential to address a significant unmet need," he said. "Importantly, this step will also help ensure that the product is used for MS patients only within the clinical trial setting prior to approval, given the differences in dosing and safety profile associated with its use in CLL and MS."

Because Lemtrada is a lower dosage of alemtuzumab than is Campath, it has a different safety profile. The MS space offers multiple therapeutic options, but each – including Lemtrada, if approved – poses potential safety issues.

Biogen Idec Inc. and Elan Corp. continually have battled reports of progressive multifocal leukoencephalopathy (PML) in patients treated with their drug, Tysabri (natalizumab), which claimed 12% of the MS market in 2011, garnering sales of $1.5 billion. Sales have picked up in recent months now that patients can use a diagnostic to predict their risk for PML.

Novartis AG markets a once-daily oral drug for MS, Gilenya (fingolimod), which launched in 2011, claiming a 4% share of the market and sales of $494 million. That product, however, sometimes presents cardiovascular side effects.

In a pivotal trial testing alemtuzumab in relapsed, remitting MS, Sanofi/Genzyme found that 15.9% of treatment-arm patients experienced autoimmune-related thyroid adverse events, compared with just 5% of control-arm patients who received Roche’s Rebif (interferon beta-1a). Meanwhile, 0.9% of the alemtuzumab recipients developed immune thrombocytopenia over a 2-year treatment period.

Genzyme, which has a management program in place to detect and treat both types of adverse events, says that even higher rates of autoimmune effects have been seen in MS testing with the antibody, but more than 90% of such cases are mild to moderate in severity and are treatable with standard therapies. At the 30-mg dosage used for CLL, the Campath label includes warnings for risk of cytopenia, infections, and infusion reactions.

Dosing, Efficacy Advantages Expected in MS

Dosing and efficacy both are expected to give Lemtrada a potential leg up in the MS space. Lemtrada would be dosed much less frequently than other MS drugs, although it would not offer the convenience of oral availability presented by Gilenya. An intravenous infusion drug, Lemtrada would be dosed at 12 mg for 5 consecutive days during the first year of treatment and then for 3 consecutive days the following year.

In the CARE-MS II trial, alemtuzumab reversed disability in nearly one-third of patients whose disease had relapsed while they received other therapy. Top-line data showed a 49% reduction in relapse rate, compared with patients treated with Rebif, along with a 42% reduction in worsening of disability. Longer-term data from the trial showed a reduction in disability, as measured by the Expanded Disability Status Scale, for treatment-arm patients, whereas control-arm patients saw increased disability.

In December 2010, while the Sanofi acquisition of Genzyme was being negotiated, Genzyme offered projections that Lemtrada would achieve 5% market share in its launch year, moving up to 10% and 12% in years 2 and 3 on the market, and an 18%-20% share by year 5. At that time, then–Genzyme executive Mark Enyedy acknowledged concerns "about managing the use of the oncology product in MS" and talked of a range of solutions, which included pulling Campath from commercialization.

Perhaps the most bullish on Lemtrada’s market potential is Stephen McGarry, an analyst with Société Générale Cross Asset Research. He projects Lemtrada’s reaching 472 million euros in sales by 2016 and continuing to grow, peaking at 1.134 billion euros in 2020. "Although we view the side effect profile as a negative relative to competing drugs in the MS space, and its route of administration is not oral, which is also a potential disadvantage, the dosing frequency and high level of efficacy more than balance those concerns in our view," he wrote in an Aug. 9 note.

Sanofi has another MS candidate, Aubagio (teriflunomide), pending at the FDA with a Sept. 12 action date. It plans to position Aubagio, an oral pill, as a convenient therapy for patients in early stages of MS, whereas Lemtrada would be targeted to those with more serious, later-stage disease.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

The key to Genzyme Corp.’s move to withdraw its leukemia drug, Campath, in anticipation of a multiple sclerosis indication seems to be working with the cancer community and establishing generous patient support.

Genzyme, the rare disease unit of Sanofi, is in the process of removing the Campath brand of alemtuzumab from commercial availability in about 50 markets, including the United States and the European Union – and the company has been transparent about its reasoning. It does not want Campath to be used off label in the multiple sclerosis setting when a lower-dose formulation of alemtuzumab obtains approval for multiple sclerosis.

But instead of courting controversy with the potentially contentious business decision, the firm has decided to make Campath available free of charge under a patient-access program. The leukemia treatment had reportedly cost in the range of $50,000-$60,000.

In an Aug. 9 letter to health care providers, Genzyme makes clear that it will stop selling Campath, not "for any reasons related to product safety, efficacy or supply, but as part of the company’s plan for bringing alemtuzumab forward as a treatment for a new indication." The company added that it "will continue manufacturing sufficient quantities of alemtuzumab to supply this patient access program."

Although sacrificing one patient community (and cancer, at that) in favor of a more lucrative one certainly seems as if it could provoke controversy, the steps Genzyme took appear to be enough to ease the company past public outcry.

Hildy Dillon, senior vice president of patient services for the Leukemia and Lymphoma Society, said that her organization was concerned when it first learned of Sanofi/Genzyme’s plans to stop selling Campath, but added that the companies had done a strong job of laying the groundwork for a transition from commercial product to one available for free under a compassionate-use protocol.

"There is an extensive patient-distribution system which they have shared with us," she said in an interview. "They’ve actually been quite supportive to us and our constituents by telling us what the distribution is and how they have communicated their plans to health care providers who treat our patients – hematology oncologists both in the community and in the major cancer centers.

"[Those doctors] are now aware of how they can access the drug since they no longer will be purchasing it, but they can contact the company directly to get whatever supply they need."

Campath Available to New Patients

Ms. Dillon said the Leukemia and Lymphoma Society was assured that Campath will be available for all patients who need it, including those who may be prescribed it for the first time after it is no longer available commercially.

"Genzyme was in touch with advocacy groups like ours to make sure we were aware of the change and how physicians will be accessing the drug," she said. "They’ve done a lot in their due diligence to inform both the physician community and the patients. ... It’s our understanding that there won’t be any shortage of supply and that the patients who need Campath will be able to get it."

By making it harder for alemtuzumab to be used in the MS setting off label, Genzyme also increases its chances of making the product (to be marketed as Lemtrada in the MS indication) much more lucrative. Campath, an anti-CD52 monoclonal antibody indicated for the treatment of chronic lymphocytic leukemia (CLL), yielded net sales of $76 million last year for Sanofi. The French pharmaceutical company bought out Genzyme for about $19.4 billion in early 2011, largely on the strength of the biotech company’s success in developing large-molecule products for rare disorders.

Industry analysts predict much bigger sales for Lemtrada, which will be provided in a 12-mg dose per treatment, compared with 30 mg for Campath. A supplemental Biologics License Application was filed at the Food and Drug Administration this past June, with a marketing authorization application sent to the European Medicines Agency in the same time frame, which means that regulatory decisions on Lemtrada are anticipated during the second quarter of 2013. Analysts widely predict initial-review approvals by the FDA and the EMA, a launch in late 2013, and the ramp-up to sales ranging between $336 million and $400 million in 2016.

No Similarity to Genentech AMD Dilemma, Genzyme Says

Sanofi/Genzyme’s dilemma regarding what to do with a useful but modestly selling drug that offers the potential to earn more in a second indication mirrors in some ways the challenge faced by Roche/Genentech Inc. with its vascular endothelial growth factor therapies Lucentis (ranibizumab) and Avastin (becavizumab). Both demonstrated potential in clinical trials for the treatment of wet age-related macular degeneration, but Roche never filed Avastin for AMD because it would undercut the Lucentis market in that indication. Lucentis costs about $2,000 per injection, while oncology drug Avastin is available in small-dose syringes for between $35 and $50 per unit.

A Genzyme spokesperson denied the similarity between the two business cases, however. "We believe the situation that we are managing with alemtuzumab is unique," he said in an e-mail exchange.

Sanofi/Genzyme made its decision on withdrawing Campath gradually, and consulted the MS and oncology communities, including patient advocacy groups, along the way, the spokesperson added.

"We are changing the way Campath is made available for its current use because we have decided to focus on bringing alemtuzumab forward for MS, where it holds the potential to address a significant unmet need," he said. "Importantly, this step will also help ensure that the product is used for MS patients only within the clinical trial setting prior to approval, given the differences in dosing and safety profile associated with its use in CLL and MS."

Because Lemtrada is a lower dosage of alemtuzumab than is Campath, it has a different safety profile. The MS space offers multiple therapeutic options, but each – including Lemtrada, if approved – poses potential safety issues.

Biogen Idec Inc. and Elan Corp. continually have battled reports of progressive multifocal leukoencephalopathy (PML) in patients treated with their drug, Tysabri (natalizumab), which claimed 12% of the MS market in 2011, garnering sales of $1.5 billion. Sales have picked up in recent months now that patients can use a diagnostic to predict their risk for PML.

Novartis AG markets a once-daily oral drug for MS, Gilenya (fingolimod), which launched in 2011, claiming a 4% share of the market and sales of $494 million. That product, however, sometimes presents cardiovascular side effects.

In a pivotal trial testing alemtuzumab in relapsed, remitting MS, Sanofi/Genzyme found that 15.9% of treatment-arm patients experienced autoimmune-related thyroid adverse events, compared with just 5% of control-arm patients who received Roche’s Rebif (interferon beta-1a). Meanwhile, 0.9% of the alemtuzumab recipients developed immune thrombocytopenia over a 2-year treatment period.

Genzyme, which has a management program in place to detect and treat both types of adverse events, says that even higher rates of autoimmune effects have been seen in MS testing with the antibody, but more than 90% of such cases are mild to moderate in severity and are treatable with standard therapies. At the 30-mg dosage used for CLL, the Campath label includes warnings for risk of cytopenia, infections, and infusion reactions.

Dosing, Efficacy Advantages Expected in MS

Dosing and efficacy both are expected to give Lemtrada a potential leg up in the MS space. Lemtrada would be dosed much less frequently than other MS drugs, although it would not offer the convenience of oral availability presented by Gilenya. An intravenous infusion drug, Lemtrada would be dosed at 12 mg for 5 consecutive days during the first year of treatment and then for 3 consecutive days the following year.

In the CARE-MS II trial, alemtuzumab reversed disability in nearly one-third of patients whose disease had relapsed while they received other therapy. Top-line data showed a 49% reduction in relapse rate, compared with patients treated with Rebif, along with a 42% reduction in worsening of disability. Longer-term data from the trial showed a reduction in disability, as measured by the Expanded Disability Status Scale, for treatment-arm patients, whereas control-arm patients saw increased disability.

In December 2010, while the Sanofi acquisition of Genzyme was being negotiated, Genzyme offered projections that Lemtrada would achieve 5% market share in its launch year, moving up to 10% and 12% in years 2 and 3 on the market, and an 18%-20% share by year 5. At that time, then–Genzyme executive Mark Enyedy acknowledged concerns "about managing the use of the oncology product in MS" and talked of a range of solutions, which included pulling Campath from commercialization.

Perhaps the most bullish on Lemtrada’s market potential is Stephen McGarry, an analyst with Société Générale Cross Asset Research. He projects Lemtrada’s reaching 472 million euros in sales by 2016 and continuing to grow, peaking at 1.134 billion euros in 2020. "Although we view the side effect profile as a negative relative to competing drugs in the MS space, and its route of administration is not oral, which is also a potential disadvantage, the dosing frequency and high level of efficacy more than balance those concerns in our view," he wrote in an Aug. 9 note.

Sanofi has another MS candidate, Aubagio (teriflunomide), pending at the FDA with a Sept. 12 action date. It plans to position Aubagio, an oral pill, as a convenient therapy for patients in early stages of MS, whereas Lemtrada would be targeted to those with more serious, later-stage disease.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

After discussions with dabigatran’s sponsor, Boehringer Ingelheim GMBH, and further study of pivotal trial data submitted with new drug application for the oral direct thrombin inhibitor, the Food and Drug Administration has revised the anticoagulant’s labeling to note that it demonstrated superiority in prevention of ischemic and hemorrhagic stroke over warfarin.

Dabigatran (Pradaxa) obtained FDA approval for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in October 2010. The label change, in the Clinical Studies section, is not because of any additional post-NDA or postmarketing data but reflects a fuller review by FDA of the data from the phase III pivotal RE-LY trial, Boehringer Ingelheim’s senior vice president for clinical development and medical affairs, John Smith, noted.

"We’ve maintained an ongoing dialogue with [the FDA’s] cardiorenal division since the approval of Pradaxa," Smith added. "What this does is ... reiterate the significant reduction of stroke that we saw in the RE-LY trial, 35% reduction of stroke, including significant 25% reduction in the risk of ischemic stroke, which is the most common stroke type in patients with atrial fibrillation." RE-LY also demonstrated significant reduction of risk for hemorrhagic stroke.

Dabigatran currently is the only approved anticoagulant drug with efficacy data superior to warfarin. It was approved with a Risk Evaluation and Mitigation Strategy, including a Medication Guide, which notes that it "can cause bleeding which can be serious, and sometimes lead to death.

AE Reporting Suggests Safety Trouble for Dabigatran

Dabigatran is safety challenged, however, especially if one gives credence to adverse event (AE) reporting. In a May 31 report, the Institute for Safe Medication Practices noted that dabigatran and warfarin ranked first and second in 2011 in serious adverse event reports to FDA by companies, clinicians, and patients. The Institute cautioned, however, that its data are not scientific – direct reporting of serious AEs to FDA is a valuable index of drug-safety risk but should not be seen as a reliable indicator of the frequency of AEs with a specific drug. FDA estimates that less than 1% of serious AEs are directly reported.

In its Quarter Watch report, the Institute noted that dabigatran accounted for 3,781 domestic serious AEs in 2011, including 542 patient deaths. These reports included 2,367 cases of hemorrhage, 291 cases of acute renal failure, and 644 of stroke. Meanwhile, warfarin was linked to 1,106 serious AEs and 72 deaths.

Later this year, Boehringer Ingelheim plans to unveil data from its long-term safety study of Pradaxa called RELY-ABLE, while it also is establishing the GLORIA-AF patient registry to study NVAF patients being treated with oral anticoagulants.

"We anticipate enrolling almost up to 10,000 patients [in GLORIA-AF], approximately a sixth of the patients globally," Mr. Smith said. "This is an opportunity to observe the use of oral anticoagulants in a real-world setting and again globally, and also allows for the serial collection of data that aren’t necessarily available from spontaneous reports."

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

After discussions with dabigatran’s sponsor, Boehringer Ingelheim GMBH, and further study of pivotal trial data submitted with new drug application for the oral direct thrombin inhibitor, the Food and Drug Administration has revised the anticoagulant’s labeling to note that it demonstrated superiority in prevention of ischemic and hemorrhagic stroke over warfarin.

Dabigatran (Pradaxa) obtained FDA approval for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in October 2010. The label change, in the Clinical Studies section, is not because of any additional post-NDA or postmarketing data but reflects a fuller review by FDA of the data from the phase III pivotal RE-LY trial, Boehringer Ingelheim’s senior vice president for clinical development and medical affairs, John Smith, noted.

"We’ve maintained an ongoing dialogue with [the FDA’s] cardiorenal division since the approval of Pradaxa," Smith added. "What this does is ... reiterate the significant reduction of stroke that we saw in the RE-LY trial, 35% reduction of stroke, including significant 25% reduction in the risk of ischemic stroke, which is the most common stroke type in patients with atrial fibrillation." RE-LY also demonstrated significant reduction of risk for hemorrhagic stroke.

Dabigatran currently is the only approved anticoagulant drug with efficacy data superior to warfarin. It was approved with a Risk Evaluation and Mitigation Strategy, including a Medication Guide, which notes that it "can cause bleeding which can be serious, and sometimes lead to death.

AE Reporting Suggests Safety Trouble for Dabigatran

Dabigatran is safety challenged, however, especially if one gives credence to adverse event (AE) reporting. In a May 31 report, the Institute for Safe Medication Practices noted that dabigatran and warfarin ranked first and second in 2011 in serious adverse event reports to FDA by companies, clinicians, and patients. The Institute cautioned, however, that its data are not scientific – direct reporting of serious AEs to FDA is a valuable index of drug-safety risk but should not be seen as a reliable indicator of the frequency of AEs with a specific drug. FDA estimates that less than 1% of serious AEs are directly reported.

In its Quarter Watch report, the Institute noted that dabigatran accounted for 3,781 domestic serious AEs in 2011, including 542 patient deaths. These reports included 2,367 cases of hemorrhage, 291 cases of acute renal failure, and 644 of stroke. Meanwhile, warfarin was linked to 1,106 serious AEs and 72 deaths.

Later this year, Boehringer Ingelheim plans to unveil data from its long-term safety study of Pradaxa called RELY-ABLE, while it also is establishing the GLORIA-AF patient registry to study NVAF patients being treated with oral anticoagulants.

"We anticipate enrolling almost up to 10,000 patients [in GLORIA-AF], approximately a sixth of the patients globally," Mr. Smith said. "This is an opportunity to observe the use of oral anticoagulants in a real-world setting and again globally, and also allows for the serial collection of data that aren’t necessarily available from spontaneous reports."

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

After discussions with dabigatran’s sponsor, Boehringer Ingelheim GMBH, and further study of pivotal trial data submitted with new drug application for the oral direct thrombin inhibitor, the Food and Drug Administration has revised the anticoagulant’s labeling to note that it demonstrated superiority in prevention of ischemic and hemorrhagic stroke over warfarin.

Dabigatran (Pradaxa) obtained FDA approval for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in October 2010. The label change, in the Clinical Studies section, is not because of any additional post-NDA or postmarketing data but reflects a fuller review by FDA of the data from the phase III pivotal RE-LY trial, Boehringer Ingelheim’s senior vice president for clinical development and medical affairs, John Smith, noted.

"We’ve maintained an ongoing dialogue with [the FDA’s] cardiorenal division since the approval of Pradaxa," Smith added. "What this does is ... reiterate the significant reduction of stroke that we saw in the RE-LY trial, 35% reduction of stroke, including significant 25% reduction in the risk of ischemic stroke, which is the most common stroke type in patients with atrial fibrillation." RE-LY also demonstrated significant reduction of risk for hemorrhagic stroke.

Dabigatran currently is the only approved anticoagulant drug with efficacy data superior to warfarin. It was approved with a Risk Evaluation and Mitigation Strategy, including a Medication Guide, which notes that it "can cause bleeding which can be serious, and sometimes lead to death.

AE Reporting Suggests Safety Trouble for Dabigatran

Dabigatran is safety challenged, however, especially if one gives credence to adverse event (AE) reporting. In a May 31 report, the Institute for Safe Medication Practices noted that dabigatran and warfarin ranked first and second in 2011 in serious adverse event reports to FDA by companies, clinicians, and patients. The Institute cautioned, however, that its data are not scientific – direct reporting of serious AEs to FDA is a valuable index of drug-safety risk but should not be seen as a reliable indicator of the frequency of AEs with a specific drug. FDA estimates that less than 1% of serious AEs are directly reported.

In its Quarter Watch report, the Institute noted that dabigatran accounted for 3,781 domestic serious AEs in 2011, including 542 patient deaths. These reports included 2,367 cases of hemorrhage, 291 cases of acute renal failure, and 644 of stroke. Meanwhile, warfarin was linked to 1,106 serious AEs and 72 deaths.

Later this year, Boehringer Ingelheim plans to unveil data from its long-term safety study of Pradaxa called RELY-ABLE, while it also is establishing the GLORIA-AF patient registry to study NVAF patients being treated with oral anticoagulants.

"We anticipate enrolling almost up to 10,000 patients [in GLORIA-AF], approximately a sixth of the patients globally," Mr. Smith said. "This is an opportunity to observe the use of oral anticoagulants in a real-world setting and again globally, and also allows for the serial collection of data that aren’t necessarily available from spontaneous reports."

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

For hepatitis C treatment, telaprevir may be suited for response-guided therapy in a larger population than boceprevir and may show greater efficacy in null responders, according to briefing materials for a Food and Drug Administration advisory committee.

Telaprevir goes before the Antiviral Products Advisory Committee on April 28; boceprevir is to be reviewed April 27.

Both of the protease inhibitors look to be headed for fairly easy reviews, with little concern raised in the FDA’s briefing documents on the efficacy.

Telaprevir and boceprevir are intended to improve therapy for chronic hepatitis C virus (HCV), adding a direct-acting antiviral to the current standard of care, a weekly injection of pegylated interferon and ribavirin, a daily tablet.

The course of therapy currently takes 48 weeks and is efficacious in fewer than half of all patients. With significant side effect profiles, including flulike symptoms and anemia, many patients discontinue therapy before completion. Both Vertex Pharmaceuticals (telaprevir) and Merck (boceprevir) hope to position their oral protease inhibitors as increasing the rate of sustained virologic response (viral cure) and reducing the duration of treatment for many patients.

Like Merck, Vertex is seeking a label that would authorize response-guided therapy (RGT) for patients who demonstrate initial improvement after receiving its drug. Vertex proposes RGT for patients who achieve extended virologic response, defined as undetectable levels of HCV RNA at weeks 4 and 12 of treatment. For telaprevir, RGT would consist of 12 weeks of combination treatment with standard of care followed by another 12 weeks on just peginterferon and ribavirin.

Vertex is asking the FDA to approve RGT in the treatment-naive population and in prior relapsers – patients who achieved cure previously on standard of care but then relapsed following treatment.

The briefing documents indicate support for Vertex’s position, which Robert W. Baird & Co. analyst Thomas Russo said would be "a clinically important, and unexpected, win at this stage," in an April 26 note.

Extended Virologic Response Seen as Good Predictor for RGT

Vertex backs its rationale for using RGT in prior relapsers who achieve extended virologic response with a retrospective viral dynamic simulation of prior relapsers using results from a pair of phase II studies included in the New Drug Application. The company found a sustained virologic response (SVR) rate greater than 90% in prior relapse patients who achieved extended virologic response after treatment with telaprevir.

"[Vertex] hypothesized that these interferon-sensitive subjects could be re-treated with a shorter course of therapy," the FDA briefing documents stated. "Because there are not adequate randomized, controlled trial data, we will ask the advisory committee to consider the evidence supporting effectiveness in this subgroup."

The FDA is asking the panelists to discuss the evidence supporting RGT at each of the drug reviews.

Telaprevir could also gain an advantage over boceprevir in the scope of the patient population, based on its effects in nonresponders. The agency questioned boceprevir’s potential efficacy in null responders in its briefing documents for that drug’s review.

The telaprevir briefing material, on the other hand, indicated that telaprevir might be significantly more effective than the current standard of care in curing this population. Vertex’s phase III REALIZE trial – which tested telaprevir in null responders, partial responders, and prior relapsers – produced a 31% SVR rate for null responders, compared with 3% for controls.

Another sign of confidence in the efficacy profile comes from an FDA reanalysis of the efficacy data from Vertex’s three phase III trials. In the treatment-naive population, the FDA determined that telaprevir produced an SVR rate of 79%, greater than the 75% reported by Vertex, in the phase III ADVANCE study. The SVR rate for the control group in that trial was unchanged, at 46%.

Signs of Concern About Safety, Specific Populations

In terms of the safety profile, the FDA is seeking the panel’s input on the significance of the rash that was commonly associated with telaprevir use, sometimes to a severe and treatment-limiting degree, as well as anemia, which occurred more frequently and sometimes more severely in patients receiving telaprevir than patients on standard of care. Anemia is also a concern with boceprevir, but not rash.

The FDA noted that rash was reported in 56% of patients receiving telaprevir, compared with 32% of patients receiving standard care. In most cases, the rash was mild to moderate, but it was severe in 1% of cases and resulted in treatment discontinuation in 6% of cases.

While anemia is a known toxicity related to treatment with ribavirin, the FDA noted that telaprevir (and boceprevir) exacerbates the potential for the disorder. Subjects treated with telaprevir had a higher frequency of anemia (36% vs. 15% of control group patients). Telaprevir-related anemia often was more severe than that occurring in patients not receiving telaprevir. Anemia-related serious adverse events were reported in 2.5% of patients receiving telaprevir but in less than 1% of control patients.

The FDA also asked the panel to comment on whether there are sufficient data to recommend that telaprevir be used in specific populations, including African Americans and patients with cirrhosis. Phase III data for telaprevir and boceprevir have suggested that the Vertex drug may be more efficacious in African American HCV patients, who historically have lower SVR rates than other patients on standard of care.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.