By Kim Coghill
Trimeris Inc. and Roche Holding Ltd. said early studies show a new class of experimental HIV drugs could offer patients resistant to other products an option in slowing the progression of their disease.
The drugs, T-20 and T-1249, have received fast-track status by the FDA, meaning review time drops from a year to six months. T-20, which inhibits fusion of the human immunodeficiency virus with host cells, is currently in Phase III clinical trials, while T-1249, also a fusion inhibitor, is in Phase I/II clinical testing. In the lab, T-1249 has been shown to be active against viruses that have developed resistance to T-20.
"The main feature of fusion inhibitors is that they are active against viruses that have become resistant to other drugs, and there's a growing need for patients who have failed other drugs," said Alex Dusek, director of marketing for Durham, N.C.-based Trimeris. "We are very encouraged by the progress we have made. These drugs complement the drugs that are out there now."
Fusion inhibitors are the first new class of drugs to be developed since introduction of protease inhibitors.
Studies released Monday, and scheduled to be publicized later this year at a conference, include data from a 16-week ongoing Phase II trial that assessed safety and antiviral activity of T-20 among moderately treatment-experienced adults (T20-206). Also unveiled were safety, activity and pharmacokinetic results from the first study investigating T-20 in HIV-1-infected children (T20-204). And data from a trial evaluating T-1249 in 72 HIV-positive, treatment-experienced patients were released.
The 16-week study results of T-20 in combination with oral antiretrovirals suggest that the addition of T-20 to a standard antiretroviral regimen was well tolerated and provided additional decreases in viral load than that provided by the antiretroviral control regimen alone.
The open-label, randomized Phase II controlled clinical study compared three doses of T-20 in combination with a regimen of oral antiretrovirals (abacavir 300mg BID, amprenavir 1200 mg BID, ritonavir 200mg BID, and efavirenz 600 mg QD) in 71 non-nucleoside reverse transcriptase inhibitor-naove and protease inhibitor- and nucleoside reverse transcriptase inhibitor-experienced HIV patients. The subjects were enrolled in one of four treatment groups: control regimen without T-20 (arm A) or control regimen with either 50 mg (arm B), 75 mg (arm C), or 100 mg (arm D) of T-20 given subcutaneously twice daily.
T-20 also was studied in 12 treatment-experienced or treatment-naove children ages 3 to 12 in a Phase I/II study conducted in conjunction with the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Data suggest that short-term (up to 12 weeks) subcutaneous dosing with T-20 was well tolerated by children and that in the highest dose group (60 mg/m2), T-20 caused rapid suppression of HIV RNA of approximately 10-fold average reduction from baseline levels in seven days.
When oral anti-HIV drugs were added to T-20, the 10-fold reduction was maintained in the majority of children who had crossed the eight-week time point.
Dusek said the companies expect an FDA filing for T-20 in the first half of 2002. T-1249 is about two years behind T-20 in development.
The third trial, a Phase I/II study to determine the safety and pharmacokinetics of T-1249, assessed patients with no concomitant antiretroviral therapy. Patients received T-1249 monotherapy for 14 days at doses ranging from 6.25 mg/day to 50 mg/day on a once- or twice-daily regimen. The results showed that T-1249 was well tolerated over 14 days, has characteristics that support once-daily dosing and confers dose-related suppression of plasma HIV RNA.
Based on the favorable tolerability and activity observed with T-1249, Trimeris and Nutley, N.J.-based Roche said they will continue to test higher doses of the drug. In the reported study, two serious adverse events possibility related to T-1249 occurred, the company said.
Trimeris' stock (NASDAQ:TRMS) closed Monday at $54.50, down 50 cents.