1 / 16

9TH INTERNATIONAL CONGRESS ON DRUG THERAPY IN HIV INFECTION November 9–13, 2008 Glasgow, UK

Efficacy and Safety of Maraviroc in Treatment-Experienced (TE) Patients Infected with R5 HIV-1: 96-week Combined Analysis of the MOTIVATE 1 & 2 Studies. 9TH INTERNATIONAL CONGRESS ON DRUG THERAPY IN HIV INFECTION November 9–13, 2008 Glasgow, UK.

affrica
Télécharger la présentation

9TH INTERNATIONAL CONGRESS ON DRUG THERAPY IN HIV INFECTION November 9–13, 2008 Glasgow, UK

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Efficacy and Safety of Maraviroc in Treatment-Experienced (TE) Patients Infected with R5 HIV-1: 96-week Combined Analysis of the MOTIVATE 1 & 2 Studies 9TH INTERNATIONAL CONGRESS ON DRUG THERAPY IN HIV INFECTION November 9–13, 2008 Glasgow, UK WD Hardy1, R Gulick2, H Mayer3, G Fätkenheuer4, M Nelson5, J Heera3, N Rajicic6, J Goodrich3 1 Cedars-Sinai Medical Center/Geffen School of Medicine, UCLA, Los Angeles, CA, USA; 2 Weill Medical College of Cornell University, New York, CA, USA; 3 Pfizer Global Research and Development, New London, CT, USA; 4 University of Cologne, Köln, Germany; 5 Chelsea & Westminster Hospital, London, UK; 6 Pfizer Inc., New York, NY, USA

  2. MOTIVATE 1 & 2: Trial Design Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + placebo OBT* + maraviroc (150 mg† QD) OBT* + maraviroc (150 mg† BID) Screening6 weeks 0 Week 48 Week 96 Patients were stratified by enfuvirtide use and HIV-1RNA < and ≥100,000 copies/mL • Patient eligibility criteria: • R5HIV-1 infection • HIV-1-RNA ≥5,000 copies/mL • Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks • Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors[PIs]) * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96

  3. MVC BID + OBT (N=426) MVC QD + OBT (N=414) Placebo + OBT (N=209) MOTIVATE 1 & 2: Percentage of Patients with HIV-1 RNA <50 copies/mL at Week 48 100 90 80 70 60 50 Patients (%) 45.5%* 43.2%* 40 30 20 16.7% 10 *P<0.0001 vs placebo 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Time (weeks) Adapted from Hardy et al. CROI 2008. Abstract 792. MOTIVATE 1 and 2 Week 48

  4. Two analyses were conducted to characterize the Week-96 combined MOTIVATE 1 and 2 populations: Efficacy Analysis This analysis includes patients receiving MVC QD and BID who had undetectable viral load (HIV-1 RNA <50 copies/mL ) at Week 48 and were followed until Week 96 Safety Analysis This analysis includes all blinded data for study participants according to their original randomization and includes data from patients who continued to receive blinded therapy beyond Week 48. It does not include any open-label treatment data. This results in a distribution of patients in the study with different exposures to blinded study drug. The study was unblinded when the last patient to be randomized reached Week 48 MOTIVATE 1 & 2: Week-96 Analyses Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Efficacy

  5. MOTIVATE 1 & 2: Trial Design Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + placebo Efficacy data include all patients who reached Week 48 with HIV-1RNA <50 copies/mL and continued on blinded therapy or open-label MVC BID OBT* + maraviroc (150 mg† QD) OBT* + maraviroc (150 mg† BID) Screening6 weeks 0 Week 96 Week 48 Patients were stratified by enfuvirtide use and HIV-1RNA < and ≥100,000 copies/mL • Patient eligibility criteria: • R5HIV-1 infection • HIV-1-RNA ≥5,000 copies/mL • Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks • Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Efficacy

  6. MOTIVATE 1 & 2: Trial Design Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + maraviroc (150 mg† QD) 239/414 (57.7%)open-label MVC BID OBT* + maraviroc (150 mg† BID) 259/426 (60.8%) open-label MVC BID Screening6 weeks 0 Week 96 Week 48 Patients were stratified by enfuvirtide use and HIV-1RNA < and ≥100,000 copies/mL • Patient eligibility criteria: • R5HIV-1 infection • HIV-1-RNA ≥5,000 copies/mL • Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks • Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC. MOTIVATE 1 and 2 Week 96 Efficacy Adapted from Hardy et al. HIV-9 2008. Presentation 0425.

  7. MVC BID + OBT (N=426) MVC QD + OBT (N=414) Placebo + OBT (N=209) MOTIVATE 1 & 2: Percentage of Patients with HIV-1 RNA <50 copies/mL at Week 96 Includes all patients who received at least one dose of study medication 100 90 Option to switch to open-label MVC BID 80 70 60 Patients (%) 46.5% 50 45.1% 41.3% 40 43.7% 43.5% 38.9% 30 20 23.0% 16.7% 10 7.2% 0 0 8 16 24 32 40 48 56 64 72 80 88 96 Time (weeks) In this analysis, non-completers were categorized as failures Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Efficacy

  8. MOTIVATE 1 & 2: Clinical Outcome At Week 96 of Patients with HIV-1 RNA <50 copies/mL at Week 48 Maraviroc groups include patients on blinded therapy and open-label MVC BID 0.6% 100 1.2% 2.8% 7.0% 9.9% 90 10.5% Discontinuation due to lack of efficacy 86.7% 80 81.4% 70 On study, not failed 60 HIV-1 RNA 50 400 copies/mL 50 Patients (%) HIV-1 RNA <50 copies/mL 40 30 20 10 0 MVC QD + OBT MVC BID + OBT N=172 N=181 Lack of efficacy = HIV-1 RNA levels of at least three times the baseline HIV-1 RNA level Does not include patients who discontinued for non-efficacy reasons: adverse events (n=4); withdrew/lost to follow up (n=8); other reasons (n=4); no discontinuation and no data at 96 weeks (N=4) Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Efficacy

  9. Two analyses were conducted to characterize the Week 96 combined MOTIVATE 1 and 2 populations: Efficacy Analysis This analysis includes patients receiving MVC QD and BID, who had undetectable viral load (HIV-1 RNA <50 copies/mL ) at Week 48 and were followed until Week 96. Safety Analysis This analysis includes all blinded data for study participants according to their original randomization and includes data from patients who continued to receive blinded therapy beyond Week 48. It does not include any open-label treatment data. This results in a distribution of patients in the study with different exposures to blinded study drug. The study was unblinded when the last patient to be randomized reached Week 48. MOTIVATE 1 & 2: Week 96 Analyses MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV-9 2008. Presentation 0425.

  10. MOTIVATE 1 & 2: Trial Design Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + placebo 98/209 (46.9%)open-label MVC BID OBT* + maraviroc (150 mg† QD) 239/414 (57.7%)open-label MVC BID OBT* + maraviroc (150 mg† BID) 259/426 (60.8%) open-label MVC BID Screening6 weeks 0 Week 96 Week 48 Patients were stratified by enfuvirtide use and HIV-1RNA < and ≥100,000 copies/mL • Patient eligibility criteria: • R5HIV-1 infection • HIV-1-RNA ≥5,000 copies/mL • Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks • Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC. Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Safety

  11. Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) MOTIVATE 1 & 2: Duration of Exposure to Study Drug Median (bars) and range (lines) of study treatment duration at indicated study time point 20 62 48 60 Week 48 48 56 20 132 73 End of Blinded Therapy 134 73 135 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 Time (weeks) Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Safety

  12. Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) Unadjusted incidence 10 8 5.3 6 4.8 4.5 4.3 Patients (%) 3.3 4 2.9 2 0 N=209 414 426 209414 426 Week 48 End of blinded therapy Adjusted incidence 9.3 10 7.1 8 4.6 Rate per 100 patient-years 6 4.1 3.6 3.5 4 2 0 Total patient-years 111 300309 60522 551 Week 48 End of blinded therapy MOTIVATE 1 & 2: Incidence of Malignancies at Week 48 and End of Blinded Therapy Includes all patients who received at least one dose of study medication If the same patient in a given treatment arm had more than one occurrence in the same event category, only the most severe occurrence was taken Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Safety

  13. Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) MOTIVATE 1 & 2: Incidence of Category C (AIDS-defining) Events at Week 48 and End of Blinded Therapy Includes all patients who received at least one dose of study medication Unadjusted incidence 10 8.1 7.7 7.5 7.0 8 5.9 5.2 6 Patients (%) 4 2 0 N= 209 414 426 209414 426 Week 48 End of blinded therapy 18 14.9 Adjusted incidence 16 14 11.0 10.0 12 Rate per 100 patient-years 10 7.6 6.2 8 5.3 6 4 2 0 Total patient-years 111 300309 160522 551 Week 48 End of blinded therapy Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Safety

  14. MOTIVATE 1 & 2: Incidence of LFT Abnormalities (Without Regard to Baseline) at Week 48 and End of Blinded Therapy ULN, upper limit of normalTotal patient-years of exposure to study drug at Week 48: Placebo + OBT 111; MVC QD + OBT 300; MVC BID + OBT 309 Total patient-years of exposure to study drug at at end of blinded therapy: Placebo + OBT 160; MVC QD + OBT 522; MVC BID + OBT 551 Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96 Safety

  15. Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) MOTIVATE 1 & 2: Adverse Events Occurring in ≥5% Patients at End of Blinded Therapy Includes all patients who received at least one dose of study medication 50 40 Unadjusted incidence Patients (%) 30 20 10 0 Nausea Vomiting Fatigue Naso-pharyngitis Upper RTI Dizziness Headache Rash 50 Exposure adjusted incidence 40 30 Rate per 100 patient-years 20 10 0 Nausea Vomiting Fatigue Naso-pharyngitis Upper RTI Dizziness Headache Rash RTI, respiratory tract infectionIf the same patient in a given treatment had more than one occurrence in the same preferred term event category, only the most severe occurrence is taken. Event counts are adjusted to 100 years of patient exposure. Includes data up to 7 days after last dose of study drug. MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV-9 2008. Presentation 0425.

  16. Efficacy Analysis Maraviroc + OBT results in durable viral suppression through 96 weeks in treatment-experienced patients with R5 HIV-1. 87% of patients in the BID arm who were fully suppressed at Week 48 remained suppressed at Week 96. Safety Analysis Pooled analyses revealed no new or unique safety signals between Week 48 and end of blinded therapy. Category C events, malignancies, and LFT abnormalities occurred with similar frequency among treatment groups when not adjusted for the longer duration of exposure in the maraviroc groups. The incidence of these events decreased between Week 48 and end of blinded therapy. After adjusting for exposure, the incidence of Category C events and malignancies was lower in the maraviroc groups compared to placebo. MOTIVATE 1 & 2 Week 96: Summary Adapted from Hardy et al. HIV-9 2008. Presentation 0425. MOTIVATE 1 and 2 Week 96

More Related