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| |  Norvir (Ritonavir) Recommended by FDA for Clearance for HIV Infections ABBOTT PARK, Ill., Feb. 29,1996 -- The Antiviral Drug Advisory Committee to the U.S. Food and Drug Administration (FDA) today voted unanimously (ten to zero) to recommend regulatory clearance for the use of Abbott Laboratories' (NYSE: ABT) HIV protease inhibitor Norvir (ritonavir) to treat advanced human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS). This indication is based on the results from a six-month study in patients with advanced HIV disease that showed a reduction in both mortality and AIDS-defining clinical events in patients receiving Norvir. In addition, the Committee recommended that the FDA grant accelerated approval for use of Norvir in patients with early HIV, contingent upon development of a study to further evaluate this patient population. "Norvir is the first protease inhibitor to demonstrate that it extends survival," says Andre Pernet, Ph.D., vice president of pharmaceutical products research and development at Abbott. "In recommending approval today, the advisory committee has taken a major step toward providing a promising new weapon in the fight against HIV and AIDS." "The FDA has shown excellent collaboration with Abbott in the advancement of Norvir from development to the approval process," says Paul Clark, senior vice president, pharmaceutical operations at Abbott. "The agency's responsiveness, guidance, and commitment to AIDS research have made it possible for Abbott to bring this powerful new therapy to patients in record development time." Protease inhibitors are a new class of drug with a mechanism of action that is different from most previously available antiretroviral treatments for AIDS. Protease inhibitors, such as Norvir, block the action of an enzyme involved in the final processing of the AIDS virus. By blocking protease activity, protease inhibitors prevent production of infectious viral particles. Among the data reviewed by the Committee were study results that showed the risk of disease progression or mortality was reduced by nearly half among patients with advanced HIV disease taking Norvir vs. patients taking placebo. Norvir is the first protease inhibitor to demonstrate a survival benefit. In the first study, a subset analysis of a randomized, double blind, placebo-controlled trial (M94-247), researchers followed 1,090 patients at 67 investigational sites in the U.S., Canada, Europe, and Australia. All patients entering the study had advanced AIDS with CD4 cell counts of less than or equal to 100 (mean CD4 cell count for these patients was 31). In the study, Norvir 600 mg or placebo was administered twice daily and was added to existing approved nucleoside therapy, if any. A total of 17.0 percent of the patients who received Norvir died or had disease progression in contrast with 34.0 percent of the patients who received placebo. Disease progression was defined as the onset of new AIDS-related illness. The six-month cumulative mortality rate among Norvir patients was 5.8 percent -- approximately half of the 10.1 percent mortality rate among patients not receiving Norvir. The clinical benefit of Norvir therapy for treatment periods longer than six months is unknown. CD4 counts were analyzed from a subset of 211 patients. Statistically significant increases in average change of CD4 count from baseline were observed with Norvir as compared to placebo at week 16. In a subset of 159 patients, Norvir produced statistically significant decreases in mean viral RNA levels compared to placebo at week 16 of the study. The HIV RNA level is an experimental measure of the amount of virus in a patient's blood. In another trial (M94-245) of patients with early-stage disease, Norvir alone, AZT alone, and the two agents in combination were compared in 356 patients randomized to one of the three treatment groups. All patients had at least one screening of CD4 lymphocytes of at least 200 cells/microliter, and at least one screening of HIV RNA level greater than or equal to 15,000 particles/milliliter. At week 16 of the study, Norvir had produced statistically significant decreases in mean average viral RNA levels compared to the combination and AZT groups. In a separate, uncontrolled open-label trial, 32 patients with advanced, previously untreated HIV infection and CD4 cell counts of less than 250 received a combined regimen of Norvir, AZT, and ddC daily. At 20 weeks of combination therapy, the median CD4 cell count had increased by 83-106 cells/microliter. The amount of virus in blood plasma (viral load), measured in viral particles, was reduced from baseline by approximately 98 percent at week 20. In addition, statistically significant mean average increases in CD4 count were observed with both groups of patients using Norvir in this trial. Norvir had a favorable safety profile in clinical trials. Common adverse events were nausea (23% to 26%), diarrhea (13% to 18%), vomiting (13% to 15%), asthenia (9% to 14%), taste disturbance (5% to 10%), anorexia (1% to 6%), paresthesias (3% to 6%), and abdominal pain (3% to 7%). Norvir should not be used in combination with many highly metabolized medications known to produce serious or life-threatening adverse events. Specific information is available in the Norvir prescribing information. Abbott Laboratories is a worldwide manufacturer of health care products, employing 50,000 people worldwide. The company researches, develops, and markets pharmaceutical, diagnostic, nutritional and hospital products.
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