By Karen Pihl-Carey
An infection-treating drug developed by Cubist Pharmaceuticals Inc. displayed positive results in a Phase II trial by showing it was as safe as comparable drugs.
Patients treated with a high dose, 6 mg/kg once a day, of daptomycin showed the same adverse reactions as patients taking vancomycin, oxacillin or lower doses of daptomycin. The Cambridge, Mass., company presented the positive interim safety data Tuesday at the American Society for Microbiology's 39th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.
Daptomycin is a novel lipopeptide antibiotic derived from Streptomyces roseosporus. It is being developed to treat life-threatening infections. Cubist initiated two clinical trials in March of daptomycin: a Phase III trial for complicated skin and soft tissue infections and a Phase II trial of bloodstream infections. The company plans to conduct two additional Phase III trials for complicated skin and soft tissue infections.
In other news from ICAAC:
¿ Abbott Laboratories, of Abbott Park, Ill., said Phase II studies of its protease inhibitor, ABT-378/ritonavir, demonstrated antiretroviral activity and tolerability in both treatment-naove and treatment-experienced HIV-positive patients. The studies showed 78 percent of protease inhibitor-experienced patients and 95 percent of antiretroviral-naove patients had HIV RNA of less than 400 copies/mL following 36 weeks of treatment.
¿ Fujisawa Healthcare Inc., of Deerfield, Ill., said its systemic antifungal agent, FK463, was effective in clinical trials in improving or clearing signs and symptoms of esophageal candidiasis, a fungal infection, at all doses tested. The drug, tested in AIDS patients, also revealed no safety-related issues. Of patients who received FK463 as a one-hour infusion for at least 10 days, 94 percent on 50-mg, 95 percent on 25-mg and 73 percent on 12.5-mg doses showed a clearing or improvement from baseline of dysphagia, dynophagia and restrosternal pain.
¿ Microcide Pharmaceuticals Inc., of Mountain View, Calif., said its beta-lactam antibiotic, a cephalosporin, has shown excellent bactericidal activity in vitro and in vivo against gram-positive bacteria, including bacteria resistant to other compounds. A total of seven papers documenting preclinical results of the company's cephalosporin are being presented. Microcide researchers also are presenting papers on the company's bacterial efflux pumps and on its fungal efflux pumps.
¿ Micrologix Biotech Inc., of Vancouver, British Columbia, said its antimicrobial bactolysin compounds were effective in controlling an ophthalmic parasite, Acanthamoeba polyphaga, which is associated with infections from contact lenses. The company plans to conduct more preclinical trials. Micrologix also said its lead bactolysin, MBI 226, was effective in reducing skin colonization by organisms, such as fungi, that are known to cause catheter-related bloodstream infections. The company is filing an investigational new drug application to undertake human clinical trials. And a Phase I study of MBI 226 showed it is safe, well tolerated, and that it eliminated 99.9 percent of bacteria commonly found on the skin and prevents bacterial growth on catheters. The company expects to initiate Phase II trials shortly.
¿ SmithKline Beecham plc, of London, said its new antibiotic gemifloxacin, Factive, demonstrated high in vitro potency against bacteria that cause community-acquired respiratory tract infections. A clinical trial program involving more than 8,000 patients is ongoing, and SmithKline Beecham intends to file a new drug application later this year.
¿ Sugen Inc., of Peapack, N.J., a subsidiary of Pharmacia & Upjohn, said its lead angiogenesis inhibitor, SU5416, had significant biologic activity in patients with AIDS-related Kaposi's sarcoma during a Phase I trial. The study also showed the drug was well tolerated without effects on viral load or other systemic HIV therapies. The company has initiated a Phase II trial in Europe and plans to start one in the U.S. shortly.
¿ U.S. Bioscience Inc., of West Conshohocken, Pa., said a Phase II trial of lodenosine, in combination with other antiretrovirals, demonstrated potent antiviral activity when administered to treatment-naove HIV-infected patients. Data from 66 patients in the multicenter, randomized trial showed 55 percent of them receiving lodenosine, along with d4T and indinavir, experienced a reduction in HIV-RNA levels to below the limit of detection at 12 weeks. There were no serious adverse events directly related to the drug, which suggests it is well tolerated, said the study's investigator, Benjamin Young, of Rose Medical Center and the University of Colorado. MedImmune Inc., of Gaithersburg, Md., recently acquired U.S. Bioscience in a deal worth about $440 million. (See BioWorld Today, Sept. 23, 1999, p. 1.)
¿ Xoma Corp., of Berkeley, Calif., said its rBPI21 (a recombinant fragment of bactericidal/permeability-increasing protein) is effective in vitro against the Chlamydia pneumoniae, a bacterium that causes pneumonia and has been associated with arteriosclerosis. Another study showed rapid in vitro activity of a novel BPI-derived antifungal compound against multiple species of Fusarium, fungi that cause deadly systemic infections.