Primary Efficacy Endpoint and Safety Results of Ibalizumab in a Phase 3 Study of Heavily Treatment-Experienced Patients With Multidrug-Resistant Human Immunodeficiency Virus-1 Infection

Abstract

Background. Despite success of combination antiretroviral (ARV) therapy, some patients fail to achieve durable viral suppression due to multidrug-resistant (MDR) human immunodeficiency virus (HIV). Ibalizumab (IBA) is the first long-acting monoclonal antibody HIV-1 entry inhibitor in Phase 3 development for treatment of MDR HIV. IBA was granted Orphan Drug status and Breakthrough Therapy designation by the FDA. Method. TMB-301 is an on-going single arm, 24-week (wk) study of IBA plus optimized background regimen (OBR) in treatment experienced patients with MDR HIV-1. The primary objective was to demonstrate antiviral activity at DAY 14 (7 days after IBA initiation). Patients were monitored for 7 days on a failing ARV regimen (control period). On DAY 7 a 2000-mg IBA loading dose was administered intrave-nously (IV) as functional monotherapy. The primary efficacy endpoint was the proportion of patients achieving a ≥0.5 log10 decrease in HIV-1 RNA from DAY 7/Baseline (BL) to DAY 14. An OBR with at least one sensitive agent was initiated on DAY 14. IBA was continued at 800 mg IV every two wks for 24 wks on study treatment. Safety and additional efficacy endpoints were evaluated. Result. Forty heavily treatment-experienced patients with MDR HIV were enrolled, mean age of 51 years, 15% female, and 45% non-white. Mean duration of HIV infection was 21 years and 28% were treated with ≥10 previous ARVs. Mean BL CD4+ T-cell count was 161 cells/μ L (50% <100 cells/μ L) and mean BL viral load (VL) was 5.0 log10 (18% BL VL ≥100,000 copies/mL). Thirty-five percent of patients required an investigational agent in OBR due to extensive resistance. 83% achieved ≥0.5 log10 decrease from BL to DAY 14 on IBA versus 3% during the control period. No treatment-related SAEs or discontinuations were reported during DAY 0-14. End-of-study safety and efficacy assessments are ongoing. [Table Presented] ∗Protocol deviations affecting analysis: incomplete Day 0 results (n = 1, excluded) and OBR started during control period (n = 1, included). Conclusion. IBA demonstrated statistically significant VL reductions compared to control in MDR HIV patients when added to a failing regimen and was well tolerated.