Sunday January 30, 8:00 am Eastern Time
Company Press Release
SOURCE: Agouron Pharmaceuticals, Inc.
Agouron's Capravirine Demonstrates Anti-HIV Activity
in Clinical Trials
SAN FRANCISCO, Jan. 30 /PRNewswire/ -- Agouron Pharmaceuticals, Inc. today reported that the investigational drug
capravirine (formerly AG1549), showed antiretroviral activity and was well-tolerated in a short course monotherapy trial of
HIV-infected patients. In a second trial to examine pharmacokinetics, capravirine achieved target antiretroviral concentrations
in plasma when administered in combination with HIV protease inhibitors. Capravirine, which demonstrates a novel HIV
resistance profile in preclinical studies, is a member of the class of agents known as non-nucleoside reverse transcriptase
inhibitors (NNRTIs). In preclinical studies, capravirine demonstrates potent antiviral activity against wild-type HIV as well as
HIV strains with mutations in reverse transcriptase, including K103N, that confer broad viral resistance to other, commercially
available reverse transcriptase inhibitors. Investigators will present results from both clinical trials this week at the 7th
Conference on Retroviruses and Opportunistic Infections in San Francisco, California.
Results of the capravirine monotherapy trial will be presented by Jose Hernandez, MD, Immunity Care and Research, LLC.,
Plantation, Florida. Capravirine was administered orally for 10 days to antiretroviral naive HIV- infected patients at doses of
either 700, 1400, or 2100 mg twice daily (BID) or 700 or 1400 mg three times daily (TID). A control arm was treated with
standard doses of the HIV protease inhibitor nelfinavir (NFV) plus AZT and 3TC. Six patients were entered into each arm,
and daily plasma HIV RNA levels were measured by the AMPLICOR(TM) HIV-1 Monitor Assay. Over the course of the
study, comparable decreases in HIV RNA were exhibited across all study arms, with mean decreases ranging from 1.1 log10
for the 700 mg TID arm to 1.69 log10 for the 2100 mg BID arm. A mean decrease of 1.65 log10 was observed in the
NFV/AZT/3TC control arm. BID and TID capravirine monotherapy treatment arms showed similar reductions in plasma HIV
RNA and were well-tolerated. The most commonly reported drug-related adverse events were nausea, vomiting, and
headache.
Mark Jacobs, MD, HIVCare at St. Francis Memorial Hospital, San Francisco, California will report results from a second trial
that examined the pharmacokinetic interaction of capravirine with the HIV protease inhibitors nelfinavir or indinavir. Forty
patients on stable anti-HIV therapy with standard doses of either nelfinavir (29) or indinavir (11) plus either AZT or d4T were
treated with capravirine for 28 days at doses ranging from 175 to 1800 mg BID (indinavir at 175 mg BID only). Capravirine
co-administered with these HIV protease inhibitors was well-tolerated and achieved the target antiviral concentrations in blood
that exhibited antiretroviral activity in preclinical studies.
Dr. Hernandez said, ''These are the first clinical data to be reported for capravirine, which exhibits a unique HIV resistance
profile preclinically. The results in decreasing viral load and achieving target antiviral concentrations will open the pathway to
further clinical development.''
Registrational clinical trials for capravirine are in progress. Agouron has exclusive rights to the development and
commercialization of capravirine in North America, Europe, and many other countries. Shionogi & Co., Ltd. maintains rights to
commercialization in Japan, South Korea, and Taiwan.
Agouron Pharmaceuticals, Inc., a wholly owned subsidiary of the Warner- Lambert Company (NYSE: WLA - news), is an
integrated pharmaceutical company committed to the discovery, development, manufacturing, and marketing of innovative
therapeutic products engineered to inactivate proteins that play key roles in cancer, AIDS, and other serious diseases. Agouron
employs more than 1200 people of whom approximately 800 are engaged in research and development.
SOURCE: Agouron Pharmaceuticals, Inc. |
