Armed with early clinical data apparently demonstrating the anti-HIVpotency of Vertex Pharmaceuticals Inc.'s protease inhibitor, thecompany and its collaborators, Glaxo Wellcome plc and KisseiPharmaceutical Co. Ltd., are planning a Phase II trial to evaluate theAIDS drug as a monotherapy.
Lynne Brum, Vertex's director of corporate communications, saiddevelopment of the protease inhibitor, VX-478, is aimed at using thedrug with other antiviral agents, such as Glaxo's FDA-approvedreverse transcriptase inhibitors, AZT and 3TC. Vertex is developingthe drug with Kissei, of Matsumato, Japan, in the Far East and Glaxo,of London, in the U.S., Europe and elsewhere.
Therapies that combine reverse transcriptase inhibitors and proteaseinhibitors are considered the most effective treatments for AIDS.Reverse transcriptase inhibitors, also called nucleoside analogues,attack HIV early in the replication cycle and protease inhibitors strikelater in the process.
Brum said Vertex, of Cambridge, Mass., and its partners, after seeingresults from Phase I/II trials of VX-478 revealing it was welltolerated at high doses and potent as a single agent, decided toexplore the drug's activity in a broader study. The six-month trial,she added, will have a safety mechanism built in so patients who donot respond to the monotherapy can switch to the combinationtreatment against which VX-478 will be evaluated.
Data from Phase I/II trials of VX-478, which were dose escalating28-day studies, was to be presented today at the InterscienceConference on Antimicrobial Agents and Chemotherapy in NewOrleans. Patients received doses of 300 mg, 900 mg or 1,200 mg.
The Phase II monotherapy trial, expected to begin in the fourthquarter of 1996, will be conducted by the AIDS Clinical TrialsGroup, which is supported by the National Institutes of Health.
An estimated 126 AIDS patients will be enrolled and divided intothree groups: one will receive 900 mg of VX-478 twice a day;another 1,200 mg twice a day; and the third, 900 mg of VX-478 twicea day in combination with AZT and 3TC.
Endpoints for the study will be reduction of viral load and increase inCD4 cell counts.
Demonstration of the effectiveness of Vertex's protease inhibitor as asingle agent could help in establishing its acceptance in the crowdedmarket of AIDS drugs.
Three protease inhibitors already are on the market and AgouronPharmaceuticals Inc., of La Jolla, Calif., expects to file for approvalof its drug next year.
Roche Holding Ltd., of Basel, Switzerland, Abbott Laboratories, ofAbbott Park, Ill., and Merck & Co., of Whitehouse Station, N.J.,received FDA market clearance for protease inhibitors within the last10 months.
Advantages of Vertex's protease inhibitor, Brum said, include bettertreatment compliance by patients and greater tissue distribution of thedrug. VX-478 also has displayed no dose limiting toxicities.
In the area of treatment compliance, administration of VX-478 is notrestricted by eating habits and is given twice a day, as are reversetranscriptase inhibitors. Other protease inhibitors are given threetimes a day and must be taken in the presence or absence of food.
VX-478 has demonstrated no adverse side effects associated withhigh dosage levels while other protease inhibitors have doselimitations based on toxicity.
Another key challenge in fighting HIV is circulation of the drug to allparts of the body where the virus resides. Brum said animal studies ofVX-478 in rats showed the protease inhibitor entered the brain andlymph systems, two areas that are difficult to reach.
In the Phase II monotherapy study of VX-478, the success of theprotease inhibitor to penetrate cerebrospinal fluid will be assessed ina subset of patients.
Glaxo also is conducting other Phase II trials to evaluate three dosagelevels of VX-478 in combination with AZT and 3TC. Results ofthose studies will help in determining the dose of protease inhibitor touse in a pivotal study slated to begin by the end of this year.
By mid-afternoon Friday Vertex's stock (NASDAQ:VRTX) was up$3.125 to $36.50.
In August 1996, Vertex raised $72 million in gross proceeds from apublic offering of 3 million shares at $24 per share. n
-- Charles Craig
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