For months, Zasloff struggled to solve the dilemma. A lonely figure reeking of shark liver, he spent his days skimming scum and injecting steroids into AIDS-infected lab animals. No approach worked. The animals’ lymphocytes stopped growing, as did the AIDS virus, but the animals simply would not eat. Anthony Fauci gave up hope: the prospect of halting a patient’s AIDS infection while having him die of starvation was obviously unacceptable. Okay, Zasloff declared at last, Okay. All was not lost. “What nature has given us,” he announced to his devastated colleagues, “is anappetite suppressant.”
Zasloff had two strikes against him, and as far as his backers were concerned, it was the bottom of the ninth. But by the mid-1990s, the sharp rise in resistance around the globe had cast peptides, his other finding, in a more favorable light. Peptides still appeared utterly impervious to all the new mechanisms of resistance that bacteria had employed. Intrigued, the FDA offered to let Magainin try peptides once more, this time on a more serious topical condition than impetigo: infected diabetic ulcers. As the FDA knew, the existing antibiotics used against these painful foot lesions caused such debilitating side effects that patients usually stopped taking them—even though the lesions, when infected, tended to invade muscle and bone, and even led to amputation of the affected limb. Now, in addition, resistance to these antibiotics was rising. Worse, the most promising of them, Trovan, would soon be pulled from the market for causing liver toxicity. Here was a real need—and market niche—that peptides seemed perfect to fill.
Because patients could suffer irreversible harm from diabetic ulcers, the FDA ruled that no placebo would be needed. Zasloff’s peptides merely had to do as well or better than one of the comparators, a powerful antibiotic called ofloxacin, which came not as a topical ointment but in oral form. Magainin breezed through phase one trials: the peptides, as shown in the previous trials, caused no harm to the skin of healthy people. To speed the process, the FDA let Magainin combine the next two phases. Roughly 1,000 patients were recruited from more than 50 medical centers in the United States between 1995 and 1998. These were very sick patients, their lesions excruciatingly painful. When doctors swabbed the lesions with a peptide solution, most of the patients seemed to improve.
As Zasloff pored over the final results, he felt encouraged, if not wildly optimistic. The topical peptides had not quite outperformed oral ofloxacin, but they’d done nearly as well. Certainly the tests had shown that MSI-78, as Magainin’s latest peptide was known, had a broad and powerful spectrum, did not provoke resistance, and had no direct side effects. The results were strong enough for Smith-Kline Beecham to sign on as a partner. SKB would market the product as Locilex. Now all Magainin needed was formal approval by an FDA advisory panel.
The panel, comprised of seven experts from various fields, met on March 4, 1999, in Silver Spring, Maryland, to spend the whole day debating the merits of Locilex. Zasloff, looking on from the audience of 300, thought the morning session went well, but the afternoon was a different story.