By Randall Osborne

An orally administered neuraminidase inhibitor markedly relieved influenza symptoms or prevented the infection in Phase II trials by Gilead Sciences Inc., and the Foster City, Calif.-based company plans to start Phase II/III studies during the upcoming winter flu season.

Gilead, which is developing GS 4104 in collaboration with F. Hoffmann-La Roche Ltd., of Basel, Switzerland, presented the results of the Phase II trials at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), in Toronto.

Studies of the drug have moved along briskly, noted Lana Lauher, Gilead's director of corporate communications. Phase I trials were done in March and Phase II in May. The drug has a clear advantage over vaccines, she added.

"The challenge with vaccines is that they must identify the outer surface of that year's flu strain, and it's highly variable from year to year," Lauher said. "Our product is going after the enzyme that the virus requires to replicate."

In the Phase II treatment study, 80 patients were randomized to one of four doses, or placebo, given once or twice daily for five days 28 hours after the volunteers had been exposed intranasally to influenza A. Duration of symptoms dropped by half with the drug, with a median time to cessation of 53 hours, compared with 95 hours for the placebo. Concentration of the virus in the blood fell more than a hundred-fold 24 hours after treatment was begun. The results, Gilead said, were statistically significant.

In the prevention study, 37 volunteers took GS 4104 or a placebo at one of two dose levels, once or twice per day for five days. Twenty-six hours after treatment began, they were exposed intranasally to influenza A. Half of the patients in the placebo control group showed the virus in their nasal passages; none in the treated group showed the virus.

Neither the physicians nor the patients knew which patients were receiving the drug as opposed to the placebo, and no dose-limiting side effects were observed.

Gilead's stock (NASDAQ:GILD) closed Monday at $45, unchanged.

In other news from ICAAC:

* Agouron Pharmaceuticals Inc., of La Jolla, Calif., reported that its HIV protease inhibitor, Viracept (nelfinavir mesylate), cleared by the FDA for marketing and made available in March, stayed potent after 12 months of treatment in a clinical trial, when used with other anti-HIV drugs. Viracept was combined with Retrovir (zidovudine or AZT) and Epivir (lamivudine or 3TC) in 297 patients. After 12 months, their viral load — the amount of HIV in the blood — dropped 99 percent for patients taking 750 mg of Viracept three times daily. In the plasma of 81 percent of the patients receiving combination therapy, viral load was reduced below the level of quantification.

* Ambi Inc., of Tarrytown, N.Y., said its antibacterial agent, the enzyme lysostaphin, eradicated all methicillin-resistant Staphylococcus aureus bacteria in animals tested during a preclinical study. The bacteria causes endocarditis, which damages heart valves. Vancomycin, which is currently used against endocarditis, was ineffective against the bacteria. The experiment used a rabbit model that mimics the condition in humans.

* Aronex Pharmaceuticals Inc., of The Woodlands, Texas, said its integrase inhibitor, Zintevir, for HIV-positive patients showed a long half-life in single and multiple doses in Phase I trials. Participants in the study were given single doses of 0.75, 1.5, 3 or 6 mg/kg intravenously over a two-hour period, or multiple doses of 1.5 or 3 mg/kg every other day for two weeks. In single-dose patients at 6 mg/kg, plasma concentrations of the drug remained at in vitro inhibitory concentration levels for up to 12 hours. In multiple-dose patients at 3 mg/kg, the drug was detectable in plasma for up to 122 hours after the final dose. A Phase I/II trial now under way will be completed early next year, Aronex said.

* BioChem Pharma Inc., of Laval, Quebec, reported that licensee Glaxo Wellcome P.L.C., of London, has been cleared by the FDA to sell Combivir, a single-tablet formulation of 3TC and AZT, for HIV-infected patients. Combivir reduces by up to six the number of tablets a patient must take daily, making compliance with drug therapy more likely. BioChem discovered Epivir and receives royalties from Glaxo Wellcome.

* Isis Pharmaceuticals Inc., of Carlsbad, Calif., reported results from its Phase I trials of the antisense cancer compound ISIS 3521/CGP64128A. Fifty-six patients with various cancers not responsive to chemotherapy showed antitumor activity in ovarian and lung cancers and lymphoma when treated with the compound at various dosing levels. No side effects related to toxicity appeared. Isis is developing the drug with Novartis A.G., of Basel, Switzerland.

* Magainin Pharmaceuticals Inc., of Plymouth Meeting, Pa., said two pivotal Phase III trials demonstrated a statistical equivalence between the company's lead compound, topical Cytolex, and an oral antibiotic to treat the infection of diabetic foot ulcers. The equivalence was recorded with respect to the primary endpoint of clinical response of the infection. A secondary endpoint was overall microbiological improvement, and results between Cytolex and the antibiotic were comparable. In February, Magainin signed an agreement worth up to $32.5 million with London-based SmithKline Beecham P.L.C. for marketing rights to the drug. A new drug application to the FDA is expected later this year.

* Merck & Co., of Whitehouse Station, N.J., reported HIV suppression below detectable levels in the blood for almost two years in 22 out of 28 AIDS patients treated with a combination of Merck's protease inhibitor, Crixivan (indinavir sulfate), AZT and 3TC. Preliminary results from another study showed 12 of 16 patients with HIV levels below detection after taking 1200 mg of Crixivan twice daily for 20 weeks. A larger study is under way involving 400 patients taking 1200 mg of Crixivan twice daily with AZT and 3TC.

* Roxane Laboratories Inc., of Columbus, Ohio, said triple combination therapy using its Viramune (nevirapine) with AZT and ddI (didanosine) significantly reduced the viral load in advanced HIV-1 patients in a Phase II trial. DDI is marketed by Bristol-Myers Squibb, of New York. Viramune, a non-nucleoside reverse transcriptase inhibitor, reduced HIV levels more when combined with the other two drugs than AZT and ddI alone. Roxane Laboratories is a sister company of Boehringer Ingelheim Pharmaceuticals Inc., in Ridgefield, Conn., which is a division of Boehringer Ingelheim G.m.b.H., of Ingelheim, Germany. *