New Drug Reviews

Oncology Review Division At The Head Of The Pack – But Can The Others Keep Up? / Analysis of drug review performance by division finds Cardiovascular & Renal Drugs Division to occupy the lower end of the spectrum. Staffing appears to be a vital component of review performance, giving weight to the researchers’ warning of impending wholesale staff turnover. / Pharmaceutical Approvals Monthly April 2012

Review Performance By The Numbers / A breakdown of performance metrics for the eight CDER review divisions analyzed by the Tufts Center for the Study of Drug Development. / Pharmaceutical Approvals Monthly April 2012

Drug Review Profile

Untargeting Xalkori? Hints Of Efficacy In ALK-Negative Patients Must Be Addressed, FDA Says / FDA approved Pfizer’s lung cancer drug for patients positive for the gene translocation – but review documents show that agency reviewers focused on the efficacy seen in the few ALK-negative patients in the pivotal trial, and want Pfizer to follow up on that signal post-marketing. Regulatory expectations for disproving effect in the non-selected population will be an important issue as more personalized medicines reach the agency. / Pharmaceutical Approvals Monthly April 2012

Therapeutic Area Updates

AACR Showcases Early Cancer Drugs, Early Use Of Biomarker Strategies / At the American Association for Cancer Research annual meeting in Chicago, data were presented on early-stage projects, some of them for the first time, as AACR displayed its growing enthusiasm for translational medicine. / Pharmaceutical Approvals Monthly April 2012

BIND Nanotherapy Shows Early Cancer Efficacy In The Clinic / Strong preclinical data for BIND-014, docetaxel-carrying particles engineered using BIND’s Accurin platform, translated into positive results against tumors not usually vulnerable to the cancer drug, the company reported at a late-breaker poster session of the American Association for Cancer Research annual meeting. / Pharmaceutical Approvals Monthly April 2012

Threshold Cancer Drug May Successfully Target Hypoxia / In combination with gemcitabine, TH-302 produced positive Phase IIb results in treatment naïve pancreatic cancer patients, according to late-breaking data presented April 2 at the AACR meeting in Chicago. / Pharmaceutical Approvals Monthly April 2012

Pipeline Updates

Allergan Seeks To Extend Botox Use To Overactive Bladder / During an R&D day March 28, Allergan highlighted its growth strategy for Botox, which includes expansion into new indications like overactive bladder; the company submitted an sBLA for the indication. / Pharmaceutical Approvals Monthly April 2012

R&D News

Bleeding Rates In TRA-2P Further Dim Outlook For Merck’s Vorapaxar / Outcomes study of about 25,000 patients shows novel antiplatelet drug reduces events but also increases major bleeding, including intracranial hemorrhage. / Pharmaceutical Approvals Monthly April 2012

Northera Ongoing Trial May Satisfy FDA Request For More Efficacy Data, Chelsea Says / In a “complete response” letter to Chelsea for use of droxidopa in treating neurogenic orthostatic hypotension, FDA requests data from an additional trial showing efficacy and durability of effect. Chelsea believes ongoing Study 306, which has had its own efficacy challenges, could fill the bill and enable an NDA resubmission as early as the first quarter of 2013. / Pharmaceutical Approvals Monthly April 2012

Genzyme/Isis’ Long-Awaited Kynamro NDA May Allay Liver Toxicity Fears / Sanofi’s Genzyme business unit and Isis submitted an NDA for mipomersen, a first-in-class cholesterol-lowering antisense drug, in an orphan population of high-risk patients with a rare genetic cardiovascular disease – with an assist from three Phase III clinical trials from other, larger, high-risk populations, to help inform regulators. / Pharmaceutical Approvals Monthly April 2012

GSK Plans To File Once-Weekly GLP-1 Albiglutide By Year-End / GSK/Human Genome Sciences’ once-weekly injectable GLP-1 agonist albiglutide succeeds in a non-inferiority study and should be filed in late 2012. But analysts critique efficacy relative to the competition and some say the diabetes drug will come to the market too late. / Pharmaceutical Approvals Monthly April 2012

Janssen Plans New U.S. Filing For Xarelto Based On Positive EINSTEIN-PE Results / In study of almost 5,000 patients, Janssen/Bayer’s novel anticoagulant proves non-inferior on efficacy compared to old standard of care, with significantly less major bleeding. A mostly one-drug, oral approach could help differentiate the drug from rivals in venous thromboembolism prevention. / Pharmaceutical Approvals Monthly April 2012

Positive Early Results For Addex Parkinson’s Drug Dipraglurant Spur Hopes For Deal / In a small, short Phase IIa study, an oral inhibitor of mGluR5 proved effective at reducing dyskinesia caused by levodopa. If future trials are positive, the drug would have a significant positive impact on Parkinson’s patients, says the Michael J. / Pharmaceutical Approvals Monthly April 2012

Profile Of Viiv’s Unboosted Dolutegravir Emerges With First Phase III Results / Viiv Healthcare/Shionogi’s once-daily, unboosted integrase inhibitor dolutegravir is efficacious and well-tolerated in the first of four Phase III HIV trials to report, a study of treatment-naïve patients. Drug poses a competitive threat to Merck’s blockbuster Isentress and Gilead’s elvitegravir, part of the four-in-one “Quad” pill. / Pharmaceutical Approvals Monthly April 2012

Sanofi/Regeneron’s PCSK9 Data Show Robust LDL Reduction, But Prompt Call For Outcomes Data / Novel inhibitor of PCSK9 lowers LDL cholesterol far beyond what can be achieved by statins. Investigators report reductions of 40% to 72% in new Phase II trial. / Pharmaceutical Approvals Monthly April 2012

Targacept, AstraZeneca Face Another Failure With NNR Class / The Targacept/AstraZeneca partnership faces another major setback as they decide not to file their neuronal nicotinic receptor modulator TC-5214 in major depressive disorder. Targacept CEO chalks the trial failure up to the gray areas of depression trial design. / Pharmaceutical Approvals Monthly April 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 April 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 April 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 April 2012

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

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

March 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 April 2012

March ANDA Approvals / Full and tentative generic drug approvals. / Pharmaceutical Approvals Monthly April 2012