Reverset active in patients failing current regimens.
In a 16-week randomized trial of nearly 200 treatment-experienced patients, 54% of those treated with 200 mg of Reverset daily experienced more than a 1.0-log drop in viral load (the trial's definition of response to therapy), compared with 40% of patients who received a placebo, Calvin Cohen, M.D., said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.
Importantly, Reverser was effective in patients with HIV resistant to other commonly used nucleoside analog reverse transcriptase inhibitors, including the two-thirds of patients with the M41L multiple thymidine analog mutation, Dr. Cohen, research director for both Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, reported at a late-breaking session.
Formerly known as D-d4FC and yet to be assigned a generic name, Reverser is well tolerated and can be given once daily, he said. Reverset is under development by Incyte Inc., which helped fund the research.
"Reverset appears to be an active, potent drug in treatment-experienced patients," Dr. Cohen told this newspaper. "Very few of our nucleosides have maintained the kind of activity we're seeing in patients with resistant virus."
Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, and moderator of the late-breaking session, agreed.
"Reverset appears to be an excellent addition to our armamentarium of nucleoside reverse transcriptase inhibitors. It is well tolerated and active against virus with various mutations," he said.
Dr. Cohen said the new trial follows earlier studies suggesting that Reverser does not appear to cause mitochondrial toxicity or elevated lactate levels--side effects associated with other NRTIs.
For the Phase IIb trial, the researchers randomized 199 treatment-experienced patients who were failing their current regimen to one of three doses of Reverset (50 mg, 100 mg, or 200 mg) or placebo. The patients had a mean baseline viral load of 31,600 copies/mL and the majority had NRTI-associated mutations: 60% had the M184V mutation, 66% had M41L, 50% had four to six thymidine analogue mutations, and 6% had K65R.
After 2 weeks, patients who received 200-mg dose of Reverset as add-on therapy achieved a drop in viral load of 0.7 [log.sub.10] copies/mL, compared with a drop of 0.03 [log.sub.10] copies/mL in the placebo arm.
By 16 weeks, patients who received 200 mg of Reverset as add-on therapy achieved a drop in viral load of 1.2 [log.sub.10] copies / mL, compared with a drop of 0.8 [log.sub.10] copies / mL in placebo patients.
The data were most dramatic in patients who did not receive lamivudine or emtricitabine, which have a similar chemical structure to Reverset, Dr. Cohen said. In this subset, 80% of patients who received Reverser achieved a barely discernible viral load of less than 50 copies/mL, compared with 25% on placebo.
Using a combination of drugs that that target different sites within the virus packs a more powerful punch, he explained.
Both the 100-mg and 50-mg doses of Reverset were less effective than the 200-mg dose, so the higher dose will be used for future study, Dr. Cohen said.
Side effects were generally mild; however, 50% of patients receiving 200 mg of Reverset with didanosine showed an elevation of pancreatic enzymes and two patients on 100 mg of Reverset developed symptomatic pancreatitis. Although the condition resolved within days of discontinuation of treatment, Reverset should not be used in combination with didanosine, Dr. Cohen said.
A third stage of the trial, which runs from week 16 to week 24 and allowed placebo patients to crossover to receive either the 100- or 200-mg dose of Reverset, will be presented in the near future, he said.
"This phase lib trial gave us what it was designed to give us--the best dose and the best regimen--as well as showing safety," Dr. Cohen said. A phase III study is planned.
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|Publication:||Family Practice News|
|Date:||Sep 1, 2005|
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