The first from a new class of HIV drugs was granted acceleratedapproval Monday as Boehringer Ingelheim Pharmaceuticals Inc.'sViramune was cleared by the FDA.
The drug, a non-nucleoside reverse transcriptase inhibitor, isindicated for use in combination with nucleoside analogues in HIV-infected adults. The accelerated approval was based on surrogatemarkers of the disease, not clinical endpoints, so clinical benefit stillmust be proved in additional studies.
But one investigator, speaking on a conference call Monday, reportedadditional data suggesting combination therapy with Viramune(nevirapine) could produce some of the best data seen in the fightagainst HIV.
Two pivotal studies in 549 patients made up the bulk of Ingelheim'sfiling. One study compared 48-week treatments of Viramune and thenucleoside analogues, AZT and ddI, to AZT, ddI and placebo inpatients with advanced disease. The triple combination therapyresulted in significantly increased CD4 cells.
The second study, BI 1046, investigated the regimens of Viramune,AZT and ddI against AZT and ddI and AZT and Viramune inpreviously untreated patients. While the filing included data afteronly six months, the 12-month data is most compelling, reportedJulio S.G. Montaner, a physician with the Canadian HIV TrialsNetwork in Vancouver, B.C.
Montaner said in the triple-combination arm of the BI 1046 study,replication of the virus was suppressed for six to 12 months in almostall patients. "I haven't seen these types of responses before," he said."In the clinic we have people who continue to respond in similarfashion at 18 months.
"This has opened the door to a new set of questions," Montaner said."Where is full suppression of replication going to take us?"
Complete results from the BI 1046 study are expected to be presentedat the upcoming AIDS conference in Vancouver, he said.
Boehringer Ingelheim Pharmaceuticals, of Ridgefield, Conn., expectsthe new drug to be available in late July. Pricing will be set when theproduct is introduced. The company is a division of Germany-basedBoehringer Ingelheim GmbH. An affiliated company, RoxaneLaboratories Inc. in Columbus, Ohio, will market Viramune.
While Viramune inhibits reverse transcriptase like the nucleosideanalogues, it has a different mechanism of action. The drug attachesdirectly to the reverse transcriptase enzyme, changing its shape andstopping its function.
The major side effect from Viramune is rash, which was experiencedby about 17 percent of patients. Few of the rashes were severe andthey came early in the course of treatment, said Maureen Myers,Ingelheim's clinical program director for virology.
Ingelheim is advising that Viramune not be combined with proteaseinhibitors, a third class of HIV drug, until more data is available.Drug interaction studies are planned or ongoing, Myers said.
Montaner said, "It is important to emphasize protease inhibitors arean important player but we have to also consider at this time thatAZT, ddI and nevirapine have been able to fully suppress viralreplication."
AZT, the first nucleoside analogue, is made by Glaxo Wellcome plc,of London. Bristol-Myers Squibb Co., of New York, makes ddI. n
-- Jim Shrine
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