By Mary Welch

A drug whose active ingredient is derived from the African clawed frog took a leap closer to market as Magainin Pharmaceuticals Inc. filed a new drug application (NDA) for pexiganan acetate, an antibiotic cream for treatment of diabetic foot ulcer infections.

Pexiganan is a member of a class of antibiotics called magainins. Its active compound, MSI-78, is a 22-amino-acid synthetic analogue of peptides that protect the skin of African clawed frogs from infection and kill bacteria by poking holes through the cell membranes.

Magainin has made at least 2,000 derivatives of the natural antibiotic, which is believed to work against Gram-negative and Gram-positive infections as well as anaerobic and fungal organisms.

The drug's former trade name was Cytolex, but upon recommendation of the FDA that name was discarded and another is being sought.

"I think the FDA thought Cytolex sounded like too many other drugs on the market," said Jay Moorin, Magainin's chairman, president and CEO. "It's part of the process. It shows they're paying attention to us.

"The [NDA] filing is a major milestone for this company," Moorin observed. "When you think that we discovered the original technology in 1987, founded the company in 1988, made the discovery of MSI-78 in our laboratories in 1990, entered the clinic in 1991, it's wonderful that everything we have worked toward has culminated in this filing.

"The magainin peptides," he added, "potentially represent the first new class of antibiotics in a decade, and there's no resistance to them. If approved as filed, the drug will have unique labeling to it as well."

The company estimates 16 million Americans have diabetes and about 15 percent will suffer from foot ulcers. Infections in the ulcers can prolong healing, leading to contiguous osteomyelitis and, ultimately, limb amputations. About 54,000 diabetics undergo lower extremity amputations in the U.S. annually.

Magainin conducted two Phase III trials with a total of 835 patients. Both trials affirmed the drug was as effective in treating diabetic foot ulcer infections as ofloxacin, a standard oral antibiotic. However, Cytolex had none of the side effects, such as insomnia, usually associated with ofloxacin, which typically is 70 to 95 percent effective in combating infections. (See BioWorld Today, March 19, 1997, p. 1.)

After completion of the second Phase III trial, the Plymouth Meeting, Pa., company said it expected to file its NDA before the end of 1997. However, it was aware the FDA was preparing new guidelines for the study of skin and skin structure infection drugs. Those guidelines were issued in July and required data on a number of primary endpoints.

"We wanted to do more analysis and spent the last eight or nine months doing that, which we added to the submission. It's as complete a submission as we can possibly make," said Moorin.

Drug May Get To Market Late Next Year

Among the data contained in the NDA filing, Moorin said, are pexiganan's "clinical response of infection, overall microbiological response of infection and therapeutic cure, which is the combination of clinical and overall microbiological cures." Magainin said its analyses showed statistical equivalence between pexiganan and ofloxacin in a majority of the endpoints.

If cleared by the FDA, Magainin and its partner, SmithKline Beecham plc, of London, expect to have the drug —with a new name — on the market by the end of next year.

SmithKline, which entered into a $32.5 million deal for North American rights to market pexiganan in February 1997, does not owe a milestone payment to Magainin for the NDA, but it will upon approval, Moorin said.

Magainin's stock (NASDAQ:MAGN) closed Monday at $5.375, down $0.375. *