InterMune Inc. reported positive results from its Phase II trial investigating Actimmune (interferon gamma-lb) as adjunctive therapy to conventional antifungal treatment of cryptococcal meningitis. Results demonstrated the addition of Actimmune to the standard regimen showed a strong trend toward more rapid clearance of cryptococcus fungus from cerebral spinal fluid (CSF) when compared to conventional antifungal therapy alone.
The results were presented at the 41st annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, which ends today.
In the study, 70 patients with acute cryptococcal meningitis were randomized to receive 100 mcg of Actimmune, 200 mcg of Actimmune or placebo three times per week for 10 weeks in addition to conventional antifungal therapy. After two weeks, fungal cultures in the CSF were negative in 38 percent of patients who received Actimmune, compared to 18 percent of placebo recipients. Adverse events were similar in all treatment groups.
Based on these positive results, InterMune, of Brisbane, Calif., said it plans to accelerate the development of Actimmune with a Phase III program in cryptococcus meningitis and additional Phase II trials in other types of systemic fungal infections, such as aspergillosis.
In other news from the conference:
¿ Bristol-Myers Squibb Co., of New York, presented data on atazanavir, a protease inhibitor, and des-F(6)quinolone (BMS 284756), both investigational compounds to treat HIV/AIDS and the community and hospital-based bacterial infections. Atazanavir is in Phase III development for the treatment of HIV/AIDS. BMS said it is the first protease inhibitor with pharmacokinetic data to support once daily dosing without the need for boosting with Ritonavir. Phase II studies have shown that atazanavir does not produce marked elevations in cholesterol and triglycerides. BMS 284756 also is being investigated in Phase III trials for the treatment of respiratory and non-respiratory infections.
¿ Dynavax Technologies Corp., of Berkeley, Calif., and its partner, Triangle Pharmaceuticals Inc., of Durham, N.C., reported positive results from a Phase I/II trial of hepatitis B prophylaxis. The double-blind study compared hepatitis B surface antigen (HbsAg) alone to it co-administered with Dynavax¿s proprietary immunostimulatory DNA sequences. At the highest dose tested, the co-administered vaccine produced protective antibody titers in 88 percent of subjects after a single immunization. Across all dose levels, 31 of 32 subjects had protective antibody levels after two doses delivered in a two-month regimen.
¿ Inhibitex Inc., of Atlanta, presented in vivo data supporting the efficacy of INH-A21 in the prevention of coagulase-negative staphylococcal infections in experimental endocarditis. INH-A21 reduced the incidence of infectious endocarditis by 60 percent compared to control. Also, animals treated with INH-A21 contained lower levels of bacteria in the blood, heart tissue and kidneys, compared to a commercially available IgG product.
¿ IntraBiotics Pharmaceuticals Inc., of Mountain View, Calif., reported positive results from a Phase IIa study of its antibiotic, iseganan hydrochloride oral solution. The study evaluated the potential of iseganan to reduce oral bacteria as a possible approach to prevent ventilator-associated pneumonia. Results from the multicenter, double-blind, placebo-controlled trial showed that iseganan was well tolerated and demonstrated significant reductions in the mean numbers of microorganisms in mechanically ventilated patients.
¿ Paratek Pharmaceuticals Inc., of Boston, said researcher Michael Draper discussed recent milestones in Paratek¿s search for tetracyclines that can combat drug-resistant malaria. Paratek is working in collaboration with Philip Rosenthal¿s laboratory at the University of California at San Francisco to identify compounds within its library of tetracycline derivatives that show activity against resistant Plasmodium falciparum.
¿ Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., reported that repeated doses of its experimental drug, PRO 140, reduced and then maintained viral loads at undetectable levels for the duration of therapy in an animal model of HIV infection. PRO 140 is a monoclonal antibody that belongs to a new class of drugs called ¿entry inhibitors¿ designed to block HIV from entering and infecting immune system cells. Progenics has a development and license agreement with Protein Design Labs Inc., of Fremont, Calif., to develop a humanized version of PRO 140 that retains the antibody¿s antiviral activity, but which is less immunogenic and therefore may be better tolerated for prolonged use in patients.
¿ Virologic Inc., of South San Francisco, said the first national assessment of HIV drug resistance revealed 78 percent of HIV patients with measurable levels of virus in their blood are infected with an HIV strain that is resistant to one or more AIDS drugs. The study used ViroLogic¿s drug resistance test, PhenoSense HIV. Researchers used Phenosense to measure drug resistance among participants in the HIV Cost and Service Utilization Study.
¿ Visible Genetics Inc., of Toronto, reported data indicating that its Trugene HIV-l Genotyping Test can be used to detect HIV drug resistance even when there are only very low levels of the virus present in a patient¿s blood. A specialized extraction technique was used to obtain sufficient genetic material for the analysis with the Trugene test. In the second study, ultracentrifugation was used and samples from all 38 patients with viral loads below 400 copies/ml were successfully genotyped using Trugene.