By Brady Huggett
Triangle Pharmaceuticals Inc. presented partial data Monday at the 8th Conference on Retroviruses and Opportunistic Infections in Chicago from its two Phase III trials for HIV, and will work with the FDA to consider its next step.
The trials compared once-daily doses of Triangle's Coviracil to twice-daily doses of lamivudine (3TC) in HIV patients receiving triple-therapy combination regimens. Coviracil, a nucleoside reverse transcriptase inhibitor, is Triangle's lead product and is being investigated for use against both HIV and hepatitis B.
Also, researchers from the Agence Nationale de Recherches sur le SIDA in France will present 64-week results of a study examining the effectiveness and tolerability of a once-daily regimen containing Coviracil, didanosine and efavirenz at the conference today.
"We are very happy with the data," David Barry, Triangle's CEO and chairman, told BioWorld Today. "But the data are under analysis. We want to give as much as we can, but we have to understand that there is a lot ongoing."
Triangle, of Durham, N.C., will meet with the FDA and discuss the possibility of filing a new drug application based on the studies already completed. But it has a 100-site, 500-patient Phase III study, named FTC-301, planned for the United States, Europe and Latin America if the FDA needs additional information. As it stands now, Barry said the planned trial would continue even if the FDA says it doesn't need anything further.
"We are looking at having a discussion with the FDA in March or April," he said. "Depending on those conversations, we will determine what kind of submission schedule we may or may not be on.
"To get all the data together and put it in a format for the FDA and make sure all the data is correct can take as long as four to five months," he added. "My own staff would be more comfortable saying it can take up to six months."
The interim data compare Coviracil and lamivudine, the most prescribed nucleoside reverse transcriptase inhibitor, measuring antiviral effect through a number of methods. Preliminary data indicate that 61 percent of patients in the Coviracil group compared to 65 percent in the lamivudine group had fewer than 50 copies/ml at week 48 on an intent-to-treat, missing equals failure basis. The incidence of virologic failure associated with resistance development was similar in both groups. Also, in study FTC-303, loss of virologic suppression anytime during the 48-week observation period occurred in 8 percent of patients in each treatment arm.
Both were well tolerated by most patients in the studies, named FTC-302 and FTC-303. Observed adverse side effects were mostly mild, except the liver toxicity seen in FTC-302 that put the trial on hold in South Africa. Barry said the liver toxicity now can be attributed to one of the combination drugs used in the study. (See BioWorld Today, April 7, 2000, and Feb. 1, 2001.)
"Liver toxicity appeared to be secondary to the use of nevirapine," Barry said. "The reason the commission stopped the study was several-fold. There were concerns that some of the patients hadn't signed the proper consent form, the study wasn't being run correctly, and other issues. That didn't mean everyone should go off the drug. We worked with them to continue [dosing] through the full 48 weeks."
Following news of the delay in South Africa in April, Triangle's stock (NASDAQ:VIRS) lost $4.50 and closed the day at $8.75. Its price has not yet recovered, and dropped 25 cents Monday to close at $7.25.
"I don't think there is a CEO of a company alive that doesn't believe his stock is undervalued," Barry said. "And I am one of them."