FDA Calendar Updates: AZN, BMY, OSUR, CPD, INSM, HLUKY

by: Mike Havrilla

Below is a summary of updates to the BioMedReports.com FDA Calendar, which includes a database of over 200 entries. The calendar was originally created by Mike Havrilla to track companies with pending new drug, biological agent, or medical device new product decisions at the FDA. With the launch of BioMedReports.com, the FDA Calendar has expanded to include the following categories: pending new submissions to the FDA (e.g. NDA, BLA, 510k, PMA, sNDA, sBLA filings), pending complete response letter (CRL) re-submissions to the FDA, and pending late-stage pivotal Phase 3 clinical trial results which are designed to support a filing for FDA approval.

On 6/25/09, H. Lundbeck (OTC:HLUKY) announced that the Company has received a Complete Response Letter (CRL) from the FDA for Serdolect (sertindole) for the treatment of schizophrenia. The Agency's CRL includes a request for additional data to best understand the appropriate patient population for which Serdolect could be made available, and the Company is currently evaluating the information in order to resolve the outstanding questions and discuss the next steps required to bring Serdolect safely to the U.S. market.

In the coming months, the Company expects to address the CRL and will work with the FDA to expedite completion of its review. On 4/7/09, a FDA Advisory Panel voted 8-2 (three panelists abstained from the vote) in favor of FDA approval for Serdolect among certain patients (such as those who do not respond to other treatments) despite concerns about heart-related risks. The Company proposed that Serdolect reduced suicide attempts, which is a major risk for patients with schizophrenia. However, the panel rejected this notion in a 12-1 vote based on a lack of convincing evidence to support the claim. Serdolect received marketing approval for the treatment of schizophrenia from the European Commission on 12/20/05 and is available in 40 countries worldwide.

European regulators have recommended approval of Onglyza (saxagliptin) a new diabetes drug from AstraZeneca (NYSE:AZN) and Bristol-Myers (NYSE:BMY), which clears the way for its launch in the coming months as such recommendations are typically endorsed by the European Commission within two or three months. The two companies announced that their drug won a positive opinion for type 2 diabetes as an as add-on therapy along with older medications such as metformin, thiazolidinedione or sulphonylurea. On 4/1/09, the Endocrinologic and Metabolic Drugs Advisory Committee for the FDA voted 10 to 2 that the companies' data ruled out the risk that the drug hastens heart attack, stroke and other problems with a final decision by the Agency expected by late July.

On 6/25/09, Insmed (NASDAQ:INSM) announced results from a Phase II clinical trial evaluating IPLEX (mecasermin rinfabate) in patients with myotonic muscular dystrophy (MMD). The randomized, double-blind, placebo-controlled Phase II trial conducted in 13 centers across the U.S. enrolled 69 patients with MMD, for a six-month period. The results of the trial indicated that IPLEX did not exhibit a statistically significant improvement in the functional measure of endurance by the six-minute walk test, muscle function, muscle strength, or quality of life in any of the tests utilized in this study. Based on the limited number of subjects enrolled with significant impairments in cognitive function, gastrointestinal function or pain, INSM was unable to reach any conclusions regarding the effects of IPLEX on these endpoints.

IPLEX did, however, demonstrate improvements in standard measures of insulin sensitivity and reductions in fasting glucose, fasting insulin, cholesterol and triglycerides, which is consistent with the expected metabolic profile of insulin-like growth factor. Administration of IPLEX also resulted in anabolic effects of increased body mass index and higher levels of testosterone. Based on the metabolic improvements observed in patients treated with IPLEX in this trial, and discussions with key opinion leaders, the Company intends to apply for a grant from the Muscular Dystrophy Association ("MDA") to facilitate an additional Phase II trial focused solely on a subset of MMD patients with severe insulin resistance who, based on the results of this trial, may be more likely to benefit from IPLEX treatment.

On 6/25/09, OraSure Technologies (NASDAQ:OSUR) provided the following updates for two diagnostic tests in development for hepatitis C virus (HCV) and an over-the-counter (OTC) diagnostic test for the detection of HIV.

During 4Q08, OSUR filed a premarket approval application (PMA) with the FDA for approval of an OraQuick HCV test for use in the professional market. The application sought approval for use of the product with multiple specimen types, including venous whole blood, fingerstick whole blood, oral fluid and other sample types. During its review of the PMA, the FDA indicated that the Company’s clinical data could potentially have been affected by bias because the same operators performed the test and interpreted the results on multiple specimen types derived from the same patient. The FDA recently concluded that additional clinical testing will be required to obtain approval of the PMA for a venous whole blood claim, and that a new clinical study will be required for approval of claims for oral fluid and other sample types.

Although the Company believes the clinical data originally submitted to the FDA is sufficient to support approval of its PMA, the Company has agreed to conduct the additional clinical testing and study mandated by the FDA in order to obtain approved claims for oral fluid, venous whole blood, and fingerstick whole blood. The exact timing and costs associated with this work will not be fully determined until after protocols are submitted and reviewed by the FDA, which should occur in the next several weeks. The Company expects first to complete the additional testing required for a venous whole blood claim and submit that data to the FDA for review and approval, while the additional study for the other specimen types is completed. The Company also plans to submit its application for CE mark for the OraQuick HCV test shortly, which is required to sell the test in Europe.

In August 2008, OSUR submitted the results of its observed use study to the FDA as part of its efforts to obtain approval for an OraQuick rapid HIV OTC diagnostic test. The observed use study was designed to assess an individual’s ability to interact with the product packaging, comprehend the instructions for use, take the test and interpret the results while a trained professional observed those activities. The observed use study was stopped after testing was completed for the first 1,000 subjects, because data from the study met the success criteria initially established in the study protocol for this phase of the trials.

The FDA recently reviewed the data from the observed use study at a meeting of its senior management. Following this meeting, the FDA contacted the Company and indicated that both the results of the observed use study and the Company’s remaining clinical activities should also be reviewed and approved by the Blood Products Advisory Committee (“BPAC”), an advisory committee to the FDA, before proceeding. The Company will meet with the FDA to discuss plans for the upcoming BPAC meeting. The Company intends to gain alignment with the FDA on the next steps required to complete and file a PMA application, before presenting a proposal at the BPAC’s meeting scheduled for November 2009.

During late afternoon trading on 6/25/09, shares of Caraco Pharma (NYSEMKT:CPD) plunged by about 50% on newswire reports that U.S. authorities seized generic medicines made by the Company at facilities in Michigan following repeated violations of manufacturing standards. The seized drugs included generic versions of heart, pain and psychiatric medicines, according to FDA officials. In late May, Caraco provided the following update on the status of a FDA inspection of the Company's Detroit manufacturing facilities stemming from an October 2008 warning letter. The following information was posted at the FDA website as part of a late afternoon news release:

U.S. Marshals, at the request of the Food and Drug Administration, today seized drug products manufactured by Caraco at the Company’s Michigan facilities in Detroit, Farmington Hills, and Wixom. The seizure also includes ingredients held at these same facilities. “The FDA is committed to taking enforcement action against firms that do not manufacture drugs in accordance with our good manufacturing practice requirements,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Compliance with these standards prevents harm to the public.”

Disclosure: No positions.