Drug Review Profile

Xarelto Tested FDA’s Comparative Efficacy Powers, But Conservative View Prevailed / J&J/Bayer’s Xarelto tested the limits of FDA’s policy on comparative efficacy, thanks to suboptimal use of the active comparator, warfarin, and the introduction of a new competitor, Pradaxa. In the medical reviewers’ view, new therapies should be as effective as existing therapies used skillfully, but division leadership would withhold approval only if the new drug were clearly inferior to approved agents. / Pharmaceutical Approvals Monthly May 2012

FDAer Eyes Improvements In Anticoagulant Trial Design / The challenges seen in the review of the new generation of oral anticoagulants suggested some avenues for improved trial design to Division of Cardiovascular and Renal Products Deputy Director Stephen Grant. The difficulty of measuring and maintaining the effectiveness for the active comparator, warfarin, in oral anticoagulant trials was a major sticking point in the review of Johnson & Johnson/Bayer AG’s novel oral anticoagulant Xarelto (rivaroxaban) for one of the most commercially significant anticoagulant markets, prevention of stroke and systemic embolism in patients with atrial fibri... / Pharmaceutical Approvals Monthly May 2012

The Xarelto Trials That Might Have Been / Johnson & Johnson/Bayer’s Xarelto (rivaroxaban) was cleared for stroke prevention in atrial fibrillation patients unencumbered by new post-marketing studies – but not for lack of suggestions. FDA reviewers had urged further studies on topics ranging from alternate dosing regimens and reversal of drug activity to transitioning to warfarin. / Pharmaceutical Approvals Monthly May 2012

Xarelto Development Timeline / A chronology of the development of Johnson & Johnson/Bayer’s anticoagulant for atrial fibrillation, the second submission for the drug. / Pharmaceutical Approvals Monthly May 2012

Xarelto Reviewers / FDA staff who participated in the review of Johnson & Johnson/Bayer’s oral anticoagulant rivaroxaban for prevention of stroke and systemic embolism in patients with atrial fibrillation / Pharmaceutical Approvals Monthly May 2012

Therapeutic Area Updates

Cancer Vaccines Headed For Mainstream / No longer the odd cousins of traditional pharmaceutical applications, a host of therapeutic cancer vaccines is working through late-stage trials with real, life-extending data already reported and the potential to create a lot of action in the oncology sector. / Pharmaceutical Approvals Monthly May 2012

Selected Active Cancer Vaccines In Development / A sampling of cancer immunotherapeutics, also called vaccines, in late-stage development illustrates the variety of approaches and mechanisms in play. / Pharmaceutical Approvals Monthly May 2012

Pipeline Review

Acorda R&D Day Explores Pipeline Opportunities / Acorda Therapeutics highlighted the other indications it has in the works for its MS drug Ampyra, as well as several early-stage compounds in other neurological indications. / Pharmaceutical Approvals Monthly May 2012

Merck Talks About Its Pipeline Post-Singulair / With its blockbuster asthma drug Singulair going off-patent at the end of the year, Merck is looking to a few key drugs to fill the revenue gap in the coming years, the company said at a recent Deutsche Bank Healthcare conference. / Pharmaceutical Approvals Monthly May 2012

R&D News

Boehringer Will Test How Pradaxa Stacks Up To The Competition In Real-World Study / Global observational study is assessing real-world experience with Pradaxa and other anticoagulants in patients with newly diagnosed atrial fibrillation who are at risk of stroke. Results are due in 2020. / Pharmaceutical Approvals Monthly May 2012

Depomed Hot Flash Drug May Finally Be On Its Way To FDA / Despite the product’s rocky history, Depomed says it is ready to file its non-hormonal hot flash treatment Serada (extended-release gabapentin) based on a recent meeting with FDA. But a mixed Phase III dataset raises doubts about approvability. / Pharmaceutical Approvals Monthly May 2012

GTx Restarts Development Of Prostate Cancer Drug Capesaris / GTx managed to convince FDA to lift its clinical hold, arguing the mid-stage prostate cancer drug would be safe to test again in patients at lower dosages than before. / Pharmaceutical Approvals Monthly May 2012

Novartis Revises U.S. Regulatory Strategy For Key Respiratory Drug / The Swiss drug maker says it has agreed with FDA on a Phase III trial design for the combination respiratory drug QVA149 and expects to file in late 2014; plan now calls for testing a twice-daily dose in addition to once-daily. / Pharmaceutical Approvals Monthly May 2012

Pfizer’s Pride-And-Joy Pain Drug Lyrica Slips In Two New Phase III Trials / One failed study tested Lyrica in a subset of difficult-to-treat patients in the approved indication of diabetic neuropathy, while another explored its use in neuropathic pain related to HIV. / Pharmaceutical Approvals Monthly May 2012

Sanofi/Genzyme MS Drug Lemtrada Scores High Against Rebif / Genzyme, a Sanofi company, set the bar high for its multiple sclerosis contender by stacking it up against Roche’s interferon beta-1a in Phase III trials and got the results it was looking for, with a filing set for this quarter. / Pharmaceutical Approvals Monthly May 2012

FDA Performance Tracker

Estimated FDA User Fee Review Goals For Pending NDAs/BLAs / Estimated user fee goals for FDA action on publicly disclosed NDAs, BLAs and efficacy supplements are calculated based on the date of receipt and assignment to standard or priority review. Resubmissions with significant new data or analyses have a 6-month goal. / Pharmaceutical Approvals Monthly May 2012

New Molecular Entities Approved In 2012 / Annual listing of novel drugs cleared by FDA’s Center for Drug Evaluation and Research. / Pharmaceutical Approvals Monthly May 2012

2012 FDA Advisory Committee Recommendations / Year-to-date tracking of drug review recommendations from FDA advisory panels, including regulatory actions. / Pharmaceutical Approvals Monthly May 2012

April Full Approvals / Full approvals of NDAs and BLAs. / Pharmaceutical Approvals Monthly May 2012

April Supplemental Approvals / Chart lists efficacy supplements and labeling supplements selected by the editors of “Pharmaceutical Approvals Monthly.” This is not a comprehensive list of all supplemental approvals. / Pharmaceutical Approvals Monthly May 2012

FDA’s ANDA Approvals / Product Sponsor Date Approved Application No. Escitalopram oxalate, EQ 5 mg base/5 mL, solution Aurobindo 4/2/2012 79-062 Acetaminophen/oxycodone HCl, 325 mg/7.5 mg and 325 mg/10 mg, tabs. / Pharmaceutical Approvals Monthly May 2012

Biologics Approved In 2012 / FDA transferred review of most therapeutic biologics to the Center for Drug Evaluation & Research in 2003. The Center for Biologics Evaluation & Research continues to review other biologics, including vaccines, cellular products, antitoxins and immunoglobulins. / Pharmaceutical Approvals Monthly May 2012

“Complete Response” Letters / FDA stopped issuing “approvable” and “not approvable” letters in favor of “complete response” letters on Aug. 11, 2008. The following chart lists “complete response” actions that were recently announced, as well as still-pending “approvable” and “not approvable” actions. / Pharmaceutical Approvals Monthly May 2012

Current Class Of Risk Evaluation & Mitigation Strategies / Here is a general outline of the REMS FDA has mandated so far, as well as a listing of drugs where it has been announced that REMS are being developed or drugs with safety issues that could invoke a REMS. / Pharmaceutical Approvals Monthly May 2012