Vertex Pharmaceuticals Inc. reported preliminary 24-week data from its Context trial and 48-week data from its Neat study, both investigating GW433908, at the 10th Conference on Retroviruses and Opportunistic Infections in Boston.
The Context trial evaluated once-a-day or twice-a-day dosing of GW433908, also called 908, boosted with ritonavir, compared to a third treatment arm of lopinavir/ritonavir twice a day in treatment-experienced patients with prior virologic failure.
The calcium phosphate ester prodrug of amprenavir, 908 was co-discovered by Vertex, of Cambridge, Mass, and GlaxoSmithKline plc, of London.
The primary objective of the Context trial was to assess antiretroviral response by measuring the time-averaged change in viral load from baseline at 24 and 48 weeks. Similar efficacy responses were seen in both the 908 and ritonavir regimens and the lopinavir/ritonavir regimen, meeting the primary endpoint of non-inferiority in this study at 24 weeks.
The Context trial is the third of three pivotal trials designed to support regulatory submission of 908. The 24-week Context results add to the 48-week results of the Neat trial and 48-week data presented in November from the Solo trial.
The Neat trial, evaluating 908 in antiretroviral therapy-na ve HIV-positive patients vs. nelfinavir, showed 109 of 166 HIV-positive patients achieved an undetectable viral load with 908, compared to 42 of 83 patients taking nelfinavir. The results were from the final analysis of 48-week data from the study in which patients received either 1,400 mg of 908 twice daily or 1,250 mg of nelfinavir twice a day.
In the trial, both groups took their respective medicine in combination with 300 mg twice a day of abacavir and 150 mg twice a day of lamivudine, both nucleoside analogue reverse transcriptase inhibitors.
The companies in December filed for approval of 908, based on three pivotal trials: Solo, Neat and Context. To date the drug has been tested in more than 1,200 people. If approved, GlaxoSmithKline will market the drug, and both companies will co-promote it in the U.S. and some European markets. (See BioWorld Today, Dec. 23, 2002.)
In other news from the conference:
• The International Antiviral Therapy Evaluation Center in Amsterdam, the Netherlands, presented results from a trial called 2NN, comparing the antiviral efficacy and safety of two NNRTIs used in combination therapy for the treatment of HIV-1-infected antiretroviral-na ve individuals. The trial showed that the NNRTIs nevirapine and efavirenz do not differ in anti-HIV efficacy with respect to HIV viral load suppression and immunological efficacy during 48 weeks of therapy. More than 1,200 patients enrolled in the study. All patients in the trial received two nucleoside analogues (d4T [stavudine] and 3TC [lamivudine]) and were randomized to one of the following arms: nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily or nevirapine 400 mg plus efavirenz 800 mg once daily.
• Tibotec-Virco NV, of Mechelen, Belgium, said TMC114, a next-generation protease inhibitor, demonstrated antiviral activity in multiple protease inhibitor (PI)-experienced HIV patients currently failing PI therapy. In the 50-patient study, the median reduction in plasma viral load was -1.35 log(10) copies/ml HIV-1 RNA after 14 days of treatment with TMC114 boosted with low-dose ritonavir (TMC114/r); the maximum reduction was -2.49 log(10). The company said the data show TMC114 is active against PI-resistant virus, and confirm previous results indicating that it is a next-generation PI that could potentially contribute to more effective HIV management.