Bristol-Myers Squibb and Merck had a setback yesterday in their plans to market a first-of-its-kind diabetes medication that aims to control blood sugar while also lowering cholesterol.
The Food and Drug Administration deferred approval of the drug, Pargluva, and asked for more information about its cardiovascular safety. The companies said the agency wanted additional information from patient trials completed since Bristol-Myers and Merck submitted data in support of their application.
The F.D.A. decision, which found the drug approvable if additional information was submitted, followed an advisory panel meeting in September in which the agency sought guidance on the drug's cardiovascular safety. Although it noted safety concerns, the panel recommended approval.
Bristol-Myers, which developed Pargluva, had hoped the drug would reinvigorate its diabetes franchise, which has been struggling against generic competition. Partly because of the company's relatively small and specialized sales force, Bristol-Myers teamed with Merck, which was to supply marketing muscle.
In a research note yesterday, the investment banking and brokerage house Friedman Billings Ramsey predicted a delay of about a year in Pargluva's introduction, to late 2006, and slightly lowered its earnings estimates for both companies.
A pool of five studies submitted by the companies revealed that patients receiving Pargluva suffered about double the risk of cardiovascular deaths or other adverse events - ranging from angina to heart attack and stroke - compared with patients receiving sugar pills or another drug.
Despite those questions about heart attack and stroke, the F.D.A.'s advisory panel last month did not include a cardiologist. The one board-certified cardiologist who normally sits on the panel reviewing diabetes drugs, Dr. Jorge Plutzky of Brigham and Women's Hospital in Boston, did not participate in the Pargluva review, citing a potential conflict of interest.
Dr. Plutzky is an expert on the class of drugs that includes Pargluva, called dual PPAR-agonists, and he has served as a consultant to both Bristol-Myers and Merck. He has also given talks on PPAR-agonists that were paid for by Bristol-Myers.
During the advisory panel meeting, members seemed confused over the cardiovascular profile of the drug, at first appearing to tilt against its approval but finally approving it 8 to 1, with some members urging additional safety studies.
In response to a reporter's question yesterday about the makeup of the advisory panel, the F.D.A. released a statement saying the agency had "the appropriate experts represented" to answer its questions about the drug. "Endocrinologists routinely treat diabetes and lipid problems in the prevention of cardiovascular disease, and so they are intimately familiar with the cardiovascular risk," the statement said.
During the September hearing, the panel members said they found comfort in the fact that beyond the five studies submitted and another five already under way, the companies planned four more, including a long-term study of cardiovascular safety.
After the panel's vote last month, Friedman Billings Ramsey lowered its 2008 sales estimate for Pargluva, to $600 million, from $950 million.
Friedman Billings cited questions over the drug's cardiovascular risks and a separate decision by the F.D.A. advisory panel that the drug should not be taken along with sulfonylureas, an oral medication to lower blood sugar that is used by about one-third of those with diabetes in the United States. The sulfonylureas stricture appeared to limit the potential market for the drug.
Yesterday, Friedman Billings lowered 2006 and 2007 earnings estimates for Bristol-Myers by 3 cents and 7 cents respectively, and lowered Merck earning estimates for 2006 by 1 cent.
Bristol-Myers fell 26 cents yesterday, to close at $22.22 a share, while Merck ended the day at $27.05 a share, down 3 cents.
