Phase III, 24-Week Results for the NEAT Trial Comparing GW433908 (908) to Nelfinavir: Presented At ICAAC
Friday September 27, 2:19 pm ET
SAN DIEGO, Sept. 27 /CNW/-- Results of the NEAT trial, an open-label, multi-center study evaluating the safety and efficacy of the investigational protease inhibitor (PI) GW433908 (908) in antiretroviral therapy-naive patients versus nelfinavir (NFV, Viracept(R)), were presented here today at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). In the trial, 73 percent of 166 HIV+ patients achieved undetectable viral load with the investigational protease inhibitor 908, compared to 54 percent of 83 patients taking nelfinavir. The 908 compound was co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals (Nasdaq: VRTX - News). Once approved, 908 will be marketed by GSK and co-promoted by Vertex Pharmaceuticals.
The results come from a 24-week interim analysis of the NEAT study in which patients were randomized to receive either 1400 mg of 908 (2 tablets twice a day) or 1250 mg of NFV (5 tablets twice a day). Both groups took the medications in combination with 300 mg twice a day (BID) of abacavir (ABC) and 150 mg BID of lamivudine (3TC). ABC and 3TC are nucleoside analogue reverse transcriptase inhibitors (NRTIs).
"Although the results are from only the first 24 weeks of this study, we think the Phase III data on the safety and efficacy of the investigational agent 908 as a therapy for HIV infection are important," said Doug Manion, M.D., vice president of clinical development, GSK.
Efficacy Results from NEAT
"At 24 weeks, 73 percent of 166 HIV-positive patients taking 908 achieved undetectable viral loads [<400copies/mL] compared to 54 percent of 83 patients taking nelfinavir," said Jeffrey P. Nadler, M.D., University of South Florida College of Medicine, Tampa, who presented the data at ICAAC. Further, 54 percent of patients in the 908 arm achieved a viral load less than 50 copies/mL, compared to 40 percent of patients taking nelfinavir.
Among people with a high viral load (>100,000 copies/mL) taking 908, 71 percent achieved a viral load <400 copies/mL and 42 percent achieved viral load <50 copies mL, versus 35 percent and 11 percent, respectively, of patients with high viral loads taking NFV, according to Dr. Nadler. Among patients with a viral load less than 100,000 copies/mL at baseline, 74 percent of patients in the 908 arm achieved an undetectable viral load, compared to 70 percent of patients in the nelfinavir arm.
Safety Results from NEAT
The incidence of dose limiting adverse events (AEs) and severe laboratory abnormalities was low in both groups. The only AE that was significantly different between the two groups was diarrhea, which was significantly more prevalent in patients on NFV (17 percent) than patients on 908 (5 percent). Most common AEs with 908 were allergy (8 percent), rash (8 percent) and nausea (5 percent).
"While the overall rates of discontinuations were similar in both study groups, more subjects withdrew due to insufficient viral response in the NFV group (11 percent) compared to the 908 group (2 percent)," said Dr. Nadler.
NEAT Study Demographics
The study population included:
-- A large proportion of patients with advanced HIV disease. Nearly 50
percent had viral loads greater than 100,000 copies at baseline, and
approximately 50 percent had CD4+ counts <200 cells/mm3, a criterion
that meets the definition of AIDS established by the Centers for
Disease Control and Prevention (CDC). Median CD4+ cell count was 214.
Further, approximately 20 percent had experienced a CDC Class C event
characteristic of advanced disease.
-- Gender diversity, with females representing 31 percent of the patient
population.
-- Ethnic diversity, including a high proportion of Hispanic patients (44
percent) and patients of African descent (31 percent).
The investigational PI 908 is the calcium phosphate ester pro-drug of amprenavir. In the study reported at ICAAC, patients in the 908 group took 2 pills BID compared to 5 pills BID in the NFV group. It is being studied in several dosing presentations: twice a day (BID), once a day (QD) in combination with the PI-booster ritonavir, and twice a day (BID) with ritonavir. In the NEAT study, 908 was taken without food or fluid restrictions, while patients are advised to take nelfinavir with food.
Ongoing Clinical Trials with 908
NEAT, the first of three pivotal trials to support regulatory approval of 908, is a Phase III, randomized, open-label, parallel-group, 48-week study. The primary endpoint is the proportion of subjects with vRNA <400 c/mL at 24 and 48 weeks. More than 1,100 people are participating in Phase III trials to test the safety and efficacy of 908. In addition to the NEAT study, two other large-scale clinical trials of 908 are under way. The SOLO study is an open- label trial that has enrolled more than 650 HIV positive, treatment-naive patients. Participants have been randomized to receive either 1400 mg of 908 plus 200 mg ritonavir QD or 1250 mg of nelfinavir BID. All also receive ABC and 3TC, two nucleoside reverse transcriptase inhibitors. The trial is being conducted at more than 50 research centers worldwide and is designed to assess the safety and efficacy of each regimen over a period of 48 weeks. Results from the SOLO trial are expected to be presented at an upcoming medical conference.
The CONTEXT study is an open-label trial in PI-experienced subjects assessing 908 dosed at 700 mg BID in combination with 100 mg ritonavir, or 908 at 1400 mg QD in combination with 200 mg ritonavir, compared to a third treatment arm of 400 mg lopinavir/100 mg ritonavir BID. Participants also receive two nucleoside reverse transcriptase inhibitors. The trial is fully enrolled with more than 300 patients and is being conducted at more than 80 research centers worldwide. The study is assessing the safety and efficacy of each regimen at 24 and 48 weeks. Results from the CONTEXT trial are expected to be presented in 2003.
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company. Vertex seeks to discover, develop, and commercialize major pharmaceutical products independently and with partners. Chemogenomics, Vertex's proprietary, systematic, genomics-based platform, is designed to accelerate the discovery of new drugs and to expand intellectual property coverage of drug candidate compounds and classes of related compounds. This approach, which targets gene families, has formed the basis for several commercial collaborations under which Vertex retains rights to downstream revenue. Vertex's first approved product is Agenerase(R) (amprenavir), an HIV protease inhibitor, which Vertex co-promotes with GlaxoSmithKline. Vertex has more than 12 drug candidates in clinical and preclinical development to treat viral diseases, inflammation, cancer, autoimmune diseases, neurological disorders and genetic disorders.
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