WASHINGTON _ A long drought in promising new AIDStherapies may soon end if Glaxo Holdings plc's experimental 3TCshows the same success in long-term, prospective clinical trials thatit has in European and American Phase II and III studies.

Scientists on Wednesday said the phase II and III findings wereremarkably consistent from study to study, suggesting that 3TC andAZT, given together suppress HIV activity; increase the blood'ssupply of critical CD4 cells, which are decimated by HIV; andprolong AZT's antiviral activity _ even after the emergence ofresistance to both 3TC and AZT.

Also, the drug appears to be relatively safe, at least when given topeople in the earliest stages of HIV disease. Only a few patients havedeveloped side effects, chiefly nausea, vomiting and headache.

But researchers cautioned against excessive optimism in light of pastdisappointments. For instance, AIDS researchers were startled twoyears ago by a French study, known as the Concord trial, whichfound that lab markers of AZT's action _ like those now beingtouted by 3TC's manufacturer as evidence of 3TC's effectiveness _turned out to be an unreliable measure of AZT's usefulness inprolonging life.

"I love the 3TC data," said Robert Schooley, of the University ofColorado, who chaired a symposium on 3TC at the Second NationalConference on Human Retroviruses and Related Infections here."But there are a lot of reasons why we have to be careful. Maybe theeffectiveness of 3TC and AZT was a bit more pronounced, andmaybe a bit more prolonged than AZT alone or in othercombinations, but we're trying not to over interpret the data."

He said the findings from recent studies _ including two U.S.studies of 352 patients announced for the first time Wednesday _mainly provide a scientific impetus for more in-depth research.

There is much to be learned. Researchers still don't understandprecisely how 3TC works, or the intricacies of its interactions withother drugs. They also don't understand why 25 percent of patientsenrolled in the initial studies dropped out, despite the apparentabsence of serious side effects.

Still, Schooley and some other 3TC researchers called the 3TC-AZTcombination an "attractive option" for current HIV sufferers, whomay obtain the experimental drug in this country as part of an "openlabel" trial even though it has not been approved for sale in the U.S.Eventually, data collected in that trial will be analyzed for furtherevidence of 3TC's effectiveness.

More than 10,000 HIV sufferers worldwide, including 8,000 in thiscountry, are already using 3TC, and demand for the drug continuesto grow, said Marc Rubin, director of infectious disease research forGlaxo, based in London.

Rubin said the company is now enrolling 350 patients a week in theU.S. open label trial. He acknowledged, however, that the mosteffective treatment regimens have yet to be worked out and that athorough assessment of the therapy's effectiveness will take years.

Like AZT, 3TC is a nucleoside analog that attacks reversetranscriptase, the enzyme that makes it possible for HIV to copyitself. Discovered by BioChem Pharma Inc., of Laval, Quebec, andlicensed to Glaxo in 1990, 3TC is now regarded as one of the mostpromising anti-HIV drugs now in the research and developmentpipeline.

The natural pairing of 3TC and AZT in the fight against a diseasethat has afflicted more than 440,000 Americans and claimed 250,000lives _ a disease, in other words, that has created a hugely profitablemarket _ was reportedly one factor that led Glaxo last month topropose a $14.2 billion marriage to AZT's manufacturer, BurroughsWellcome Co., of Research Triangle Park, N.C.

Wellcome rejected the bid as "inadequate." (For more details, seeBioWorld Today, Jan. 27, 1995, p. 1.)

Rubin declined to comment on the proposal except to say that Glaxohas publicly expressed its position that a merger would be in the bestinterest of both companies. "We've always worked well withWellcome, and I expect we will continue to work well withWellcome in the future," he said.

Both companies have played significant roles in designing andcarrying out studies of the 3TC-AZT combination, researchers said.

Scientists who attended the session expressed optimism over 3TC'sprospects. "It's very promising," said David Cooper, director ofAustralia's National Centre in HIV Epidemiology and ClinicalResearch. "It's at least as good as AZT and ddI or AZT and ddC, andthe toxicity is low." n

-- Steve Sternberg Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.