BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4+ T-cells. AI438011 is an ongoing Phase 2b, randomized, controlled trial investigating the safety, efficacy and dose–response of four doses of BMS-663068 vs atazanavir/ritonavir (ATV/r) in treatment-experienced (TE) HIV-1-infected subjects. At Week 24/48 BMS‑663068 had similar response rates across all doses and to ATV/r and was generally well tolerated. We report results through Week 96.
TE adults (≥1 week exposure to ≥1 ARV) with viral loads (VL) ≥1,000 c/mL and susceptibility to BMS-663068 (BMS-626529 IC50 <100 nM), raltegravir (RAL), tenofovir disoproxil fumarate (TDF), and ATV were randomized equally to four BMS-663068 arms (400 or 800 mg BID; 600 or 1200 mg QD) and a control (ATV/r 300/100 mg QD), each with a backbone of RAL 400 mg BID+TDF 300 mg QD. BMS-663068 1200 mg QD was selected as the open-label continuation dose after Week 48 and pooled efficacy and safety results for BMS-663068 are included.
254 subjects were randomized and 251 treated across all arms. Median age was 39 years, 60% were male, 62% were non-white. Median baseline (BL) VL was 4.85 log10 c/mL (43% ≥100,000 c/mL); median CD4+ T-cell count was 230 cells/µL (38% <200 cells/µL). In total, 67% (167/251) subjects completed 96 weeks of therapy. At Week 96, 61% of BMS-663068- and 53% of ATV/r-treated subjects had HIV-1 RNA <50 c/mL (mITT; Table). In the observed analysis, 90% of BMS-663068- and 90% of ATV/r-treated subjects had HIV-1 RNA <50 c/mL (Table). Observed virologic response rates for BMS-663068 vs ATV/r by BL VL <100,000 c/mL were 87% vs 95%, respectively, and by BL VL ≥100,000 c/mL were 94% vs 80%, respectively. Mean increase in CD4+ T-cell count from BL through Week 96 was 219 cells/µL for BMS-663068 and 250 cells/µL for ATV/r. BMS-663068 was generally well tolerated and no BMS-663068-related AEs led to discontinuation (D/C).
At Week 96, BMS-663068 continued to show similar virologic response rates (mITT and observed) and immunologic reconstitution to ATV/r in TE subjects. BMS-663068 was generally well tolerated and no BMS-663068-related AEs led to D/C. These results support the ongoing Phase III trial evaluating BMS-663068 in heavily TE adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining) due to resistance, tolerability issues and contraindications (NCT02362503).