If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  FDA Approves Agenerase For HIV Treatment RESEARCH TRIANGLE PARK, NC -- April 16, 1999 -- The United States Food and Drug Administration has granted accelerated approval to Glaxo Wellcome’s Agenerase(TM) (amprenavir), a new protease inhibitor with proven antiviral activity, for use in combination with other antiretrovirals for the treatment of HIV infection. Agenerase is the first protease inhibitor to be approved in more than two years. Agenerase has been studied in clinical trials of previously untreated patients, as well as patients who have received prior reverse transcriptase inhibitor and protease inhibitor therapy. "There is a great need for dosing flexibility with antiretroviral therapy. Agenerase has a long half-life and can be dosed twice a day. This aspect of the drug, and the fact that it is generally well-tolerated, make Agenerase an important new treatment for HIV," said Jeff Goodgame, M.D., principal investigator, Central Florida Research Initiative. "Agenerase increases the options for naive and treatment-experienced HIV patients and may help to simplify combination therapy by offering less restrictive dosing patterns." The approval of Agenerase is based on 24-week analyses of two well-controlled clinical trials. Agenerase achieved viral load less than or equal to 400 copies/ml (Roche Amplicor HIV Monitor(R)Test) in therapy-naive, NNRTI and NRTI-experienced patients when given in triple combination therapy. Mutations conferring resistance to Agenerase have been selected in vitro and were also obtained from patients treated with Agenerase. The key mutation associated with resistance to Agenerase, 50V, has not been observed in protease-inhibitor therapy-experienced patients, or as a naturally-occurring variant in persons living with HIV. In addition, several mutations are required in order for significant resistance to occur. The clinical relevance of the genotypic and phenotypic changes associated with therapy with Agenerase has not been established. Varying degrees of cross-resistance have been observed between Agenerase-selected resistant variants and other protease inhibitors. Agenerase in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV RNA levels and CD4 cell counts in controlled studies up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV RNA or disease progression with Agenerase. The recommended dose of Agenerase is eight 150-mg capsules twice daily. Most other protease inhibitors are indicated for three times daily dosing. Agenerase can be taken with or without food, but high fat meals should be avoided. The safety of Agenerase was studied in over 1,400 patients who received Agenerase in combination with a variety of other antiviral agents. Agenerase should not be used with some drugs and it may cause serious and/or life-threatening reactions with other drugs. See full prescribing information for specific drug interactions. The majority of adverse events were of mild to moderate intensity. The most frequently reported adverse events were nausea, diarrhea, vomiting, rash and perioral paresthesia. Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have occurred in one percent of patients treated with Agenerase. As with other protease inhibitors, Agenerase may be associated with acute hemolytic anemia, diabetes mellitus and hyperglycemia. In both Phase III studies severe laboratory abnormalities occurred infrequently. Preliminary data suggest that there is no clinically significant effect on lipid profile with Agenerase.
|
