These results come from the final analysis of 48-week data from the NEAT study in which patients were randomized to receive either 1400 mg of 908 (2 tablets) twice daily (BID) or 1250 mg of nelfinavir (5 tablets) BID. 908 was taken without food or fluid restrictions. Both groups took these medications in combination with 300 mg BID of abacavir (ABC) and 150 mg BID of lamivudine (3TC). ABC and 3TC are nucleoside analogue reverse transcriptase inhibitors (NRTIs).
"These 48-week data on the safety and efficacy of the investigational agent 908 in a relatively advanced and diverse treatment-naïve patient population demonstrate that, once approved, 908 will be a promising new addition to current therapy options for individuals infected with HIV," said Doug Manion, M.D., vice president of Clinical Development, GSK.
Efficacy Results from NEAT
"At 48 weeks, 66 percent of 166 HIV-positive patients taking 908 achieved undetectable viral load (<400 copies/mL), compared to 51 percent of 83 patients taking nelfinavir. More subjects on the NFV group, 28 percent, were considered virologic failures compared to those subjects receiving 908, 14 percent," said Jeffrey P. Nadler, M.D., University of South Florida College of Medicine, Tampa, a NEAT trial investigator. Further, 55 percent (n=92) of patients in the 908 arm achieved a viral load <50 copies/mL, compared to 41 percent (n=34) of patients taking nelfinavir. Among the approximately 50 percent of patients with high baseline viral loads (>100,000 copies/mL), 67 percent of those taking 908 achieved vRNA <400 copies/mL and 55 percent achieved vRNA <50 copies/mL, versus 35 percent and 24 percent, respectively, among patients taking nelfinavir, according to Dr. Nadler. Among patients with vRNA <100,000 copies/mL, 65 percent in the 908 arm achieved an undetectable viral load (<400 copies/mL), compared to 59 percent in the nelfinavir arm. During the 48 weeks of study, the median change from baseline in CD4+ cell counts was 201 cells/mm3 in the 908 group and 216 cells/mm3 in the nelfinavir group.
Safety Results from NEAT
The incidence of adverse events (AEs) and severe laboratory abnormalities was low in both treatment groups. The only AE that was significantly different was diarrhea, which was significantly more prevalent in patients receiving nelfinavir (18 percent) than in patients receiving 908 (5 percent). The overall incidence of other drug-related Grade 2-4 AEs was comparable between the two groups. The other most common drug-related AEs with 908 were rash (7 percent) and nausea (5 percent); with NFV they were nausea (4 percent) and vomiting (4 percent).
No subject in the 908 group experienced a Grade 3-4 elevation in triglycerides or total cholesterol. No patients in the NFV group experienced Grade 3-4 elevations in total cholesterol, and one percent of the NFV patients experienced a Grade 3-4 elevation in triglycerides. While some elevation in lipid values was observed in both groups, the median values at week 48 remained within the optimal or near optimal range according to the guidelines of the National Cholesterol Education Program (NCEP), with the exception of triglyceride levels, which were in the borderline high range for the nelfinavir group (>200 mg/dL for triglycerides).
NEAT Study Demographics
The study population included:
The investigational PI, 908, is the calcium phosphate ester pro-drug of amprenavir. Patients in the 908 group took 2 pills BID compared to 5 pills BID in the nelfinavir group. 908 is being studied in several dosing presentations, all without food restrictions: twice a day (BID) and once a day (QD) in combination with low dose ritonavir.
Summary of Clinical Trials with 908
More than 1,200 people have participated in three Phase III trials to test the safety and efficacy of 908: NEAT, SOLO and CONTEXT. The SOLO study was an open-label trial with 649 HIV+, treatment-naïve patients. Participants were randomized to receive either 1400 mg of 908 plus 200 mg ritonavir (908/r) QD or 1250 mg of nelfinavir BID.
All also received the two NRTIs, ABC and 3TC. The trial, conducted at more than 100 research centers worldwide, was designed to assess the safety and efficacy of each regimen over a period of 48 weeks. Results from the SOLO trial were presented in November 2002 at the 6th International Congress on Drug Therapy in HIV Infection in Glasgow, United Kingdom.
The CONTEXT study is an open-label trial in PI-experienced subjects with prior virologic failure 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 NRTIs. The trial is fully enrolled with more than 300 patients and is being conducted at more than 100 research centers worldwide. The study is assessing the safety and efficacy of each regimen at 24 and 48 weeks. Results at 24 weeks from the CONTEXT trial were also presented today in Boston.
Once approved, GSK will market 908, and GSK and Vertex will co-promote it in the United States and key markets in Europe.
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.
This press release may contain forward-looking statements, including that 48-week interim analysis of the NEAT and SOLO studies in GlaxoSmithKline's pivotal program for 908 is indicative of a promising clinical and commercial outlook for 908, once approved. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex's actual results to vary materially. These risks and uncertainties include, among other things, the risk that approval will be delayed or will not be obtained, that 908 will not be commercially successful, and those other risks listed under Risk Factors in Vertex's form 10-K filed with the Securities and Exchange Commission on April 1, 2002.
AT A GLANCE
66% of HIV+ patients achieved undetectable viral load with the investigational protease inhibitor 908, compared to 51% of patients taking nelfinavir (NFV).
67% of patients in the 908 arm with high baseline viral load (>100,000 copies/mL) achieved undetectable viral load, compared to 35% of patients with high baseline viral load in the NFV arm.
The only significantly different adverse event (AE) between the two treatment arms was diarrhea, which was much more prevalent in patients receiving NFV (18 percent) than in patients receiving 908 (5 percent). Other most common drug-related AEs with 908 were rash (7 percent) and nausea (5 percent); with NFV they were nausea (4 percent) and vomiting (4 percent).
The NEAT study population was treatment-naive and ethnically and gender diverse, approximately 50% of whom had advanced HIV disease.
Data from NEAT add to the 24-week results of the CONTEXT trial presented today and 48-week data from the SOLO trial presented in November 2002.
Mary Faye Dark, GlaxoSmithKline
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Beth Schlesinger, Public Communications Inc.
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