Presentation on theme: "Efficacy of maraviroc (MVC) administered once-daily or twice-daily with boosted protease inhibitors to treatment-experienced patients S Taylor, 1 J Arribas,"— Presentation transcript:
Efficacy of maraviroc (MVC) administered once-daily or twice-daily with boosted protease inhibitors to treatment-experienced patients S Taylor, 1 J Arribas, 2 C-F Perno, 3 R Burnside, 4 L McFadyen, 5 D Hardy, 6 H-J Stellbrink, 7 DA Cooper, 8 J-M Molina, 9 E van der Ryst, 5 J Heera, 4 H Valdez 10 1 Birmingham Heartlands Hospital, Birmingham, UK; 2 Hospital La Paz, Madrid, Spain; 3 University of Rome, Tor Vergata, Italy; 4 Pfizer Inc., Groton, CT, USA; 5 Pfizer Global Research and Development, Sandwich, Kent, UK; 6 Cedars-Sinai Medical Center/Geffen School of Medicine-UCLA, Los Angeles, CA, USA; 7 ICH Study Center, Hamburg, Germany; 8 University of New South Wales and St Vincent’s Hospital, Sydney, Australia; 9 Assistance Publique-Hopitaux de Paris, Paris, France; 10 Pfizer Inc., New York, NY, USA
Percentage of patients with HIV-1 RNA <50 copies/mL in the MOTIVATE studies through 48 weeks Hardy et al, Abstract 792, CROI, 2008. 042028 Patients (%) 40 30 20 0 16.7% 43.2%* 45.5%* 100 90 80 70 60 50 10 81216243236404448 *P <0.0001 vs placebo Time (weeks) Placebo + OBT (N=209) MVC QD + OBT (N=414 ) MVC BID + OBT (N=426 ) Option to switch to open-label MVC BID In this analysis, non-completers and missing data were categorized as failures OBT, optimized background therapy
MOTIVATE: Effect of boosted PIs on MVC Cavg 1 Weatherly et al, Poster 17a, IWCPHIV, 2008. 2 Kakuda et al, Antimicrob Agents Chemother, 2011; 55(5) 2290-6. Phase 2b/3 MVC 150 mg QD vs Phase 2a 300 mg BID monotherapy 1 Horizontal line = median Phase 2a 300 mg BID in asymptomatic HIV-1 infected subjects as target exposure (133 ng/mL) DRV/r boosts MVC exposures comparable to LPV/r and ATV/r in formal drug interaction studies in healthy volunteers 2 800 600 400 200 0 MVC C avg (ng/mL) FPV/r QD 78 72 n = Median = ATV/r QD 56 109 IDV/r QD 6 134 LPV/r QD 107 149 SQV/r QD 35 174
Rationale for once-daily MVC with a boosted PI in treatment-experienced patients MVC monotherapy data show comparable antiviral responses with both 300 mg QD and BID 1 MVC 150 mg QD with boosted PIs achieved similar or greater concentrations compared to 300 mg BID without inhibitors/inducers 2 MVC when dosed QD with select boosted PIs may offer treating physicians and patients the option of simplified dosing of MVC 1. Fätkenheuer et al, Nat Med, 2005. 2. Weatherley et al, Poster 17a, IWCPHIV, 2008.
Objective To determine in a post-hoc analysis, whether the efficacy of QD MVC in combination with select boosted PIs (excluding TPV/r and FPV/r) is comparable to MVC BID at week 48
Analysis population MOTIVATE patients n=1049 CCR5 + patients by enhanced sensitivity Trofile assay (ESTA) n=841 Boosted PI patients n=448 MVC QD n=187 MVC BID n=176 Placebo n=85 Boosted PI patients: patients whose baseline regimen included ATV/r, IDV/r, LPV/r, or SQV/r FPV/r patients n=149 MVC QD n=50 MVC BID n=56 Placebo n=43 Remainder patients n=244 ( TPV/r, unboosted or no PI) MVC QD n=98 MVC BID n=96 Placebo n=50
Patient subgroup analyses: Number of active drugs in background regimen at baseline (wOBTss < or ≥ 1) Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) 40 20 100 80 60 0 35.9 3.7 26.3 Placebo MVC 150 mg QD MVC 150 mg BID 58.1 59.7 35.7 wOBTss <1 n/N=23/6420/561/2771/11968/11715/57 ≥1 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily; wOBTss, weighed optimized background therapy susceptibility score
Patient subgroup analyses: First-time use of a selected boosted PI Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) 40 20 100 80 60 0 59.0 Placebo MVC 150 mg QD MVC 150 mg BID 56.3 All boosted PI first use n/N=49/838/39 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily Atazanavir/r first use Lopinavir/r first use 20.5 59.4 57.1 22.2 69.0 58.1 16.7 40/7119/324/1816/2820/292/1218/31
Patient subgroup analyses: Use of a selected boosted PI to which virus is susceptible Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) 40 20 100 80 60 0 59.0 Placebo MVC 150 mg QD MVC 150 mg BID 56.5 All boosted PI susceptible n/N=36/619/29 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily Atazanavir susceptible Lopinavir susceptible 31.0 58.3 65.0 23.1 63.3 55.3 33.3 35/6214/243/1313/2019/305/1521/38
Conclusions Comparable efficacy was demonstrated in subjects treated with MVC 150 mg QD or BID compared to placebo in combination with a boosted PI (except TPV/r and FPV/r) Efficacy was maintained with MVC QD or BID with a boosted PI compared to placebo in patients: –with high screening VL or low baseline CD4+ cells –receiving >1 other fully active drug (wOBTss >1) –receiving selected boosted PI for the first time or with documented viral susceptibility to the selected boosted PI MVC administered QD in combination with select boosted PIs may be a potential option for treatment- experienced patients seeking a simplified treatment regimen
Acknowledgments Thank you to all study participants and investigators who participated in the MOTIVATE 1 and MOTIVATE 2 studies. Editorial support was provided by Dr Clemence Hindley at Complete Medical Communications and funded by ViiV Healthcare
Your consent to our cookies if you continue to use this website.