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No New Year's Joy from FDA

MedpageToday

The usual year-end rush of FDA approvals has been slowed by regulatory speed bumps as encountered by Pfizer's updated pneumococcal conjugate vaccine Prevnar 13, and Basilea's anti-MRSA agent ceftobiprole.

The news that ceftobiprole, which is licensed by Cilag GmbH International, a Johnson & Johnson company, was facing regulatory problems was not surprising, since the FDA had already warned that it was displeased with the way Johnson & Johnson was managing clinical trials of the drug.

The Prevnar delay was more puzzling, since many thought that Pfizer's vaccine was on course for prompt approval when FDA advisers gave it a thumbs-up by a vote of 10 to 1 in early November.

The prescription drug user fee (PDUFA) deadline for FDA action was Dec. 30.

In a prepared statement announcing the Prevnar delay, Emilio Emini, PhD, Pfizer's chief science officer in its vaccine division, said the FDA had not yet completed its review of the Biologics License Application for Prevnar 13, but it put a positive spin on the news noting "we remain confident that the data in the BLA support approval."

Pfizer first marketed a pneumococcal vaccine in 2000 and when it entered the market the original Prevnar vaccine offered protection against more than 80% of invasive pneumococcal disease in infants and toddlers.

But by 2007 new serotypes had emerged and disease caused by those non-Prevnar serotypes increased.

The updated vaccine targets the serotype 19A, the most common of those emergent strains, five other new strains, and the seven serotypes contained in the original conjugate.

The panel's positive vote came after committee members decided that the vaccine offered protection against a wider array of serotypes than the earlier vaccine, despite the fact that action against two of the new strains failed to meet clinical endpoints for efficacy in Pfizer's clinical trials.

No other vaccines are approved to protect against the same strains of invasive pneumococcal disease.

Otitis media could, however, prove to be the sticking point since the FDA panel did not seem convinced that the new vaccine would prevent ear infections. The current version was approved for the otitis media indication and the company said that the same protection was present in Prevnar 13.

In its statement Pfizer said Prevnar 13 has been approved for use in infants and young children in 34 countries. Further pediatric regulatory filings for Prevnar 13 are in advanced stages of review in various countries spanning six continents. Prevnar 13 is also being studied in global Phase III clinical trials in adults, with regulatory submissions expected in 2010.

While Pfizer is hanging fire awaiting the agency's final word on Prevnar, the outlook for Basilea's ceftobiprole is grim and has resulted in legal action.

In a complete response letter sent Dec. 30, the FDA told the company that it "has completed the review of the application and has determined that it cannot approve the application in its present form."

In a statement issued from company headquarters in Basel, Switzerland, Basilea said the FDA determined that data from two studies managed by Johnson & Johnson were unreliable.

"The FDA in its Complete Response Letter noted that, in addition, the FDA's Division of Scientific Investigations (DSI) determined that Johnson & Johnson PRD failed to adequately monitor the clinical investigators' conduct of these studies, as outlined in its Warning Letter issued earlier this year to Johnson & Johnson PRD," according to the Basilea statement.

Basilea said that the "deficiencies" cited by the FDA, prompted it to pursue a breach of license agreement against Johnson & Johnson.

"The company submitted a Request for Arbitration under the License Agreement for ceftobiprole in February 2009. Basilea's claims under arbitration include that Johnson & Johnson PRD breached the License Agreement by, among other things, causing the delay in the approval of ceftobiprole in the U.S. and E.U. Basilea's initial significant damage claims, including milestone payments and additional damages, in the arbitration will increase as a result of this further delay," the company said.