Conference Reports for NATAP

14th CROI Conference on Retroviruses and Opportunistic Infections Los Angeles, California Feb 25- 28, 2007 Back

Motivate 1 Study: Efficacy and Safety of Maraviroc plus Optimized Background Therapy In Viremic, ART-Experienced Patients Infected With CCR5-Tropic HIV-1: 24-Week Results of Phase 2b/3 Studies       Reported by Jules Levin CROI Feb 27, 2007, Los Angeles   Brief Summary: In Motivate 1 study which took place in the USA & Canada patients were randomized to maraviroc once or twice daily plus OBT (optimized background therapy) or placebo plus OBT:....Viral load reduction at week 24 was -1.82 log for patients on MVC QD+OBT (N=232), -1.95 log for patients on MVCBID+OBT (n=235), and -1.03 for patients on placebo+OBT (n=118)..... 60.4% <400 c/ml for patients on MVC BID +OBT (p<0.0001 versus placebo + OBT), 54.7% <400 c/ml for patients on MVC QD +OBT (p<0.0001 versus placebo + OBT), 31.4% <400 c/ml on placebo+OBT..... CD4 increase was 110 on MVC & 52 on placebo....you can see safety profile below in the tables but there is no indication from the data for safety concerns; and the adverse events reported below appear normal. Motivate 2 is the other international study and IÕll present the results in the report.   Presentation No. 104bLB MOTIVATE 1 USA and Canada Efficacy and Safety of Maraviroc plus Optimized Background Therapy In Viremic, ART-Experienced Patients Infected With CCR5-Tropic HIV-1: 24-Week Results of Phase 2b/3 Studies J Lalezari1, J Goodrich2, E DeJesus3, H Lampiris4, R Gulick5, M Saag6, C Ridgway7, M McHale7, E van der Ryst7, and H Mayer2 on behalf of the MOTIVATE 1 Study Group 1Quest Clinical Research, UCSF, San Francisco, CA, USA; 2Pfizer Global Research and Development, New London, CT, USA; 3Orlando Immunology Center, Orlando, FL, USA; 4San Francisco Veterans Affairs Medical Center, UCSF, San Francisco, CA, USA; 5Weill Medical College of Cornell University, New York, NY, USA; 6University of Alabama at Birmingham, Birmingham, AL, USA; 7Pfizer Global Research and Development, Sandwich, UK   Presentation No. 104aLB MOTIVATE 2 Europe, Australia and USA M Nelson1, G FŠtkenheuer2, I Konourina3, A Lazzarin4, N Clumeck5, A Horban6, M Tawadrous7, J Sullivan3, H Mayer7, and E van der Ryst3 on behalf of the MOTIVATE 2 Study Group 1Chelsea & Westminster Hospital, London, UK; 2Universitaetsklinik Koln, Koln, Germany; 3Pfizer Global Research and Development, Sandwich, UK; 4IRCCS San Raffaele, Milan, Italy; 5C.H.U. St-Pierre, Brussels, Belgium; 6Szpital Zakazny Centrum Diagnostyki i Terapii AIDS, Warsaw, Poland; 7Pfizer Global Research and Development, New London, CT, USA   BACKGROUND   Oral CCR5 antagonist   Potent antiviral activity in vitro and in vivo against CCR5-tropic (R5) HIV-1 including multi-drug-resistant HIV-1, but not CXCR4-tropic (X4) or dual/mixed-tropic (D/M) HIV-1: -- Generally well tolerated in healthy volunteers and patients in Phase 1/2a clinical trials -- Maximum HIV-1 RNA reductions of > 1 log10 copies/mL in patients with R5 HIV-1 treated with maraviroc monotherapy at ³ 100 mg BID   MOTIVATE 1 and 2: Ongoing Phase 2b/3 trials assessing the safety and efficacy of maraviroc in ARV-experienced patients -- Primary endpoint at 24 weeks: Mean change from baseline in HIV-1 RNA   Trial Design 601 patients in Moticate 1 and 475 patients in Motivate 2 were randomized 1:2:2 to OBT+placebo OBT+ Maraviroc (150 mg once daily, QD) or OBT+Maraviroc (150 mg BID, twice daily)   * OBT = optimized background therapy of 3Š6 ARVs (PK boosting doses of RTV not counted as an ARV) Patients receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC   MOTIVATE 1 (North America): 24 Week Results   Demographics and Baseline Characteristics Includes all patients who received at least one dose of study medication Median Cd4 was 150-168 Median HIV-1 RNA was 4.85 log 43% had Fuzeon in regimen 66-72% had 2 or less active drugs in OBT   Mean Change in HIV-1 RNA from Baseline at Week 24 Includes all patients who received at least one dose of study medication   Viral load reduction at week 24 was -1.82 log for patients on MVC QD+OBT (N=232), -1.95 log for patients on MVCBID+OBT (n=235), and -1.03 for patients on placebo+OBT (n=118). Percentage of Patients with Undetectable HIV-1 RNA -- 60.4% <400 c/ml for patients on MVC BID +OBT (p<0.0001 versus placebo + OBT) -- 54.7% <400 c/ml for patients on MVC QD +OBT (p<0.0001 versus placebo + OBT) -- 31.4% <400 c/ml on placebo+OBT   Mean Change in CD4 Count from Baseline to Week 24 CD4 increase was 110 on MVC & 52 on placebo. Mean Change in HIV-1 RNA from Baseline at Week 24 According to Screening HIV-1 RNA and Enfuvirtide Use in OBT* Regardless of whether viral load was <100,000> viral load reductions were similar: patients with <100,000 at baseline-- -2.02 log on MVC QD, -2.10 log on MVC BID, -1.45 log on placebo; there was little difference in viral load reduction whether patients were on Fuzeon or not. However, for patients receiving MVC+Fuzeon viral load reduction was -2.08 vs -1.31 for patients on placebo+OBT without Fuzeon. Of note the patients in the table below who received Fuzeon included patients both who were na•ve & not na•ve to Fuzeon. However, in speaking with Pfizer if you look at Fuzeon na•ve patients the same no difference was seen.