By Lisa Seachrist

Washington Editor

Nearly five months after it was given, the FDA took the advice of its advisory committee and issued Magainin Pharmaceuticals Inc. a non-approvable letter for its lead antibiotic product, Locilex cream (pexiganan acetate cream 1 percent).

The Plymouth Meeting, Pa.-based company's drug was reviewed by the Anti-Infective Drugs Advisory Committee in March as a treatment for diabetic foot ulcers. That committee ultimately voted 7 to 4 against recommending the drug for approval. (See BioWorld Today March 5, 1999, p. 1.)

The news that the agency concurred with the committee sent the company's stock (NASDAQ:MAGN) plummeting 54 percent Monday as it closed at $1.625, down $1.875 a share.

"We're obviously disappointed," said Dennis Molnar, director of finance and business development for the company. "We still believe in this product. There is a need for new agents to treat diabetic foot ulcers and there is a need for a new class of antibiotics."

The agency didn't detail exactly what it required for pexiganan to be granted approval. However, the FDA did say it would like to see additional clinical trials of the product. Molnar said that company is interpreting that to mean Phase III trials.

"The agency didn't specify what type of clinical trial would be needed and whether we would have to have a placebo-controlled trial," Molnar said. "Right now, we need to meet with the agency to find out what they want to see from us. We also need to find out what our marketing partner, SmithKline Beecham, plans for this product."

Pexiganan is a synthetic cationic (positively charged) peptide, known as a magainin, comprised of 22 amino acids. The compound is based on naturally occurring peptides found in the African clawed frog. All animals, including humans, produce some kind of magainin, typically in the skin, lungs, oral mucosa, tongue and intestines.

Magainins work by boring holes in the negatively charged membrane of bacteria and fungi. The compounds work on both gram-positive and gram-negative bacteria, as well as some fungi. In addition, the company found that micro-organisms don't develop resistance to the products.

The FDA panel had no safety issues with the drug. But it also said the data didn't demonstrate efficacy - used following surgical debridement - in trials pitting it against the oral antibiotic ofloxacin and surgical debridement. The panel suggested the company test the drug against surgical debridement to establish its efficacy.

However, at the time Magainin devised the study protocol, it determined that because infected diabetic foot ulcers can lead to amputations, performing a placebo- controlled study, rather than an active-agent control, wouldn't be ethical.

"It would be difficult for us to do an additional Phase III study from a resources standpoint," Molnar told BioWorld Today. "If we need to do a placebo-controlled study, I'm not sure where we are going to find an IRB [institutional review board] to approve that."

Molnar said the company had other magainin compounds in preclinical development, but given its resources, any additional development probably would be related to pexiganan. In addition to the magainin platform, the company is in Phase II development of an anti-angiogenic compound, squalamine, as a therapy for solid tumors. The company also has a respiratory program focused on the role of interleukin-9 in asthma.