By Kim Coghill

Washington Editor

Two companies that have faced setbacks in their drug approval processes are scheduled today to present their cases before FDA advisory committees.

One product, known as FluMist, Aviron Inc.¿s flu vaccine that is inhaled through the nose, is expected to win recommended approval Friday from the Vaccine and Related Biological Products Advisory Committee, following a two-day meeting. But today, the Endocrinologic and Metabolic Drug Advisory Committee is expected to recommend against approval of Amylin Pharmaceuticals Inc.¿s experimental diabetes drug Symlin.

On Wednesday, each of the committees released summaries indicating preliminary findings.

Responding to the negative news about Symlin contained in an FDA briefing document, Joe Cook, chairman and CEO of San Diego-based Amylin, said he wouldn¿t discuss details of the committee¿s briefing document except to say that the information in the report is one person¿s opinion.

Trading on Amylin¿s stock (NASDAQ:AMLN) was held Wednesday, with it closing unchanged at $7.95.

¿The key thing I want to emphasize about this meeting is the [FDA] really does look to these meetings as an unbiased, scientifically based, open forum for input and debate about the agents being considered,¿ Cook told BioWorld Today. ¿It is very important for a company like us to be able to have the chance to present in an unbiased open forum.¿

Amylin is asking to market Symlin (pramlintide acetate) as an adjunctive therapy to insulin for the treatment of people with Type I or Type II diabetes. Symlin is a synthetic version of human amylin, a hormone secreted with insulin by the beta cells in the pancreas.

The drug has had a rocky history. Amylin was developing it in partnership with Johnson & Johnson, of New Brunswick, N.J. After investing $175 million and failing to produce a workable product, J&J withdrew in 1998, leaving the smaller company to fend for itself. (See BioWorld Today, March 3, 1998.)

Amylin changed the dose of the drug, initiated other trials, and according to the company, ended up being successful in Phase III trials where Symlin demonstrated statistically significant improvements in blood glucose control without weight gain in insulin-using people. The company said the reductions in blood glucose were achieved with no increase in severe hypoglycemic event rates compared to the control group.

But Fariba Ghodsian, managing director of health care research at Roth Capital Partners Inc. in Los Angeles, said whether the product was statistically significant wasn¿t really the issue raised in the advisory committee¿s briefing document.

¿From a statistical standpoint, our view is that the drug could have had a chance,¿ Ghodsian told BioWorld Today. ¿But from a safety and efficacy standpoint, especially a safety standpoint, I think it is extremely unlikely at this time that the drug will get approved.¿

According to the briefing document, ¿severe hypoglycemia was much more of a problem in patients on pramlintide than in patients on insulin alone and was associated with major trauma, motor vehicle accidents and death. Driving-related events associated with hypoglycemia were reported four times more frequently in pramlintide-treated patients than in patients on insulin alone. The severity of hypoglycemia in pramlintide-treated patients seems out of proportion to the small reduction in HbA1c (glycated hemoglobin).¿

The briefing document said pramlintide reduces postprandial hyperglycemia during the first few weeks of treatment but that the long-term reduction in HbA1c is ¿trivial¿ and completely overshadowed by the risk of severe hypoglycemia.

Furthermore, the document said the trials ¿deviated so much from good medical practice that they provide little insight into which patients would benefit from pramlintide or how pramlintide should be used.¿

Although Cook wouldn¿t discuss specifics before the hearing, on Wednesday he said the study was complex because it includes patients using insulin, a powerful glucose-lowering agent. ¿So in a blinded clinical setting, you cannot tell people not to change their insulin and if they vary their insulin, they confound the final results you may be trying to show in your trial,¿ he said. ¿We believe we have amassed a compelling set of data that should lead regulatory authorities to consider favorably approving this agent.¿

Aviron¿s FluMist Appears In Good Shape

If early indications are correct, Aviron, of Mountain View, Calif., could be sitting on a gold mine with its vaccine, FluMist.

Aviron¿s stock (NASDAQ:AVIR) closed Wednesday at $40.80, up $4.95 or 13.8 percent.

Douglas Lind, a physician with Morgan Stanley in New York, said by 2005, FluMist likely will generate about $320 million in sales, but some other analysts are calling FluMist a potential $500 million- to billion-dollar product.

The vaccine is expected to win recommended approval in the two-day committee hearing that begins today.

¿You never know until they vote, but I¿ve always thought it is likely that this product will get approved for a couple of reasons,¿ Lind said. ¿They had some of the top investigators doing the clinical trials and American Home Products signed on as a partner with full knowledge of the data. Also, the current management team came from Merck & Co. with full knowledge of the data and the chief scientific officer, Harry Greenberg, was a former chairman of an advisory panel. It doesn¿t get any better than that.¿

Aviron would market FluMist with Wyeth Lederle Vaccines, a business unit of the pharmaceutical division of American Home Products Corp., of Madison, N.J.

FluMist is similar to flu vaccines currently on the market in that it is needed only once a year, Lind said. But the big difference is FluMist in inhaled through the nose so it is painless.

If approved without any delays, FluMist could make it to the market in time for the coming flu season, Lind said.

Aviron began pivotal trials in 1996 for FluMist. Two years later, the FDA rejected the company¿s biologics license application, citing a need for more manufacturing data. (See BioWorld Today, Sept. 2, 1998.)

The company resubmitted an application last fall and it was accepted in December, triggering a milestone payment from Wyeth Lederle Vaccines.

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