Less than a month after the FDA approved Hoffmann-LaRoche's Invirase for AIDS, Abbott Laboratories has fileda new drug application (NDA) with the regulatory agencyfor ritonavir, an HIV protease inhibitor similar to Roche'scompound.
Invirase (saquinavir) was the first protease inhibitorapproved Dec. 7, 1995. The FDA cleared the drug formarketing in a record 97 days after Hoffmann-La Roche,of Nutley, N.J., submitted its NDA.
Abbott, of Abbott Park, Ill., is the second drug maker toseek approval of a protease inhibitor, but Merck & Co., ofWhitehouse Station, N.J., is not far behind. Merck isexpected to file its NDA in early 1996.
Protease inhibitors, which attack HIV replication at theend of the cycle, are a new class of AIDS drugsconsidered more potent and more safe than the nucleosideanalogs, such as AZT, which strike the virus earlier in thereplication process.
Experts have said a combination of nucleoside analoguesand protease inhibitors likely will become the standardtherapy for battling the disease.
Among the studies Abbott conducted to support its NDAwas a trial evaluating ritonavir in combination with AZTand ddc. The former is made by London-based GlaxoWellcome plc and the latter nucleoside analog is made byHoffmann-La Roche, which is a subsidiary of RocheHoldings Ltd., of Basel, Switzerland.
Abbott officials said the combination therapy"demonstrated more potent antiviral activity than anysingle agent or combination of agents previously testedwith ritonavir" in patients who had not received priortreatment.
Laureen Cassidy, spokeswoman for Abbott, said thecompany also is conducting a clinical trial testingritonavir in combination with Roche's protease inhibitor.
Clinical trial evaluation of the AIDS drugs is based ontheir performance against surrogate markers; that is,whether CD4 cell counts increase and viral loads decreasein a patient's blood.
Wall Street analysts have said protease inhibitorsdeveloped by Abbott and Merck are more potent thanRoche's, but have greater adverse side effects.
Abbott officials listed ritonavir's side effects as diarrhea,nausea, vomiting, fatigue and tingling around the mouth.
A second generation of protease inhibitors is beingdeveloped by Agouron Pharmaceuticals Inc., of La Jolla,Calif., and Vertex Pharmaceuticals Inc., of Cambridge,Mass. Those drugs are expected to be even more potentand more safe than the first-generation compounds. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.