Multi-drug resistant (MDR) HIV-1 has been associated with a higher risk of disease progression and death. Antiretroviral agents (ARVs) with new mechanisms of action are necessary for patients with MDR HIV-1. The humanized monoclonal antibody, ibalizumab (IBA), is a long-acting ARV with a unique binding specificity allowing it to block viral entry into host cells. In the registrational Phase 3 study in MDR HIV-1 patients, TMB-301, IBA previously showed significant viral load (VL) reductions 7 days after initial dosing when added to a failing ARV regimen. Here, we describe the sustained efficacy, safety and tolerability of IBA through Week (wk) 24 of treatment.
TMB-301 is an open-label study investigating the antiviral activity and safety of IBA plus an optimized background regimen (OBR) in treatment-experienced patients with MDR HIV-1. Following a 7-day monitoring period of patients on a failing ARV regimen, an intravenous (IV) loading dose of 2000 mg IBA was administered (functional monotherapy). On Day 14, an OBR was added with at least one additional sensitive agent and patients continued on an IV maintenance dose of 800 mg IBA every two wks for 24 wks. Efficacy and safety endpoints were evaluated.
Enrolled patients (n=40) had a median Baseline (BL) VL of 4.6 log10 (18% BL VL ≥100,000 copies/mL) and a median BL CD4+ T cell count of 73 cells/µL. Resistance testing at BL showed 53% and 35% of patients had exhausted ≥3 and 4 ARV classes, respectively, and 16% of patients had HIV-1 resistant to all approved ARVs. 43% of patients required an investigational agent in OBR. At Wk 24, using the ITT – Missing Equals Failure (ITT-MEF) analysis, the mean change from BL VL was -1.6 log10 with 55% and 48% of patients having a ≥1 log10 and ≥2 log10 reduction, respectively. Viral load <50 and <200 HIV RNA copies/mL was reached in 43% and 50% of patients, respectively. Other efficacy outcomes are presented on Table 1. Most treatment-emergent adverse events reported were mild to moderate in intensity. Nine patients had a serious adverse event, of which one (immune reconstitution inflammatory syndrome) was considered drug-related. Nine patients discontinued the study prior to completion.
Bi-weekly IBA plus OBR maintained virologic efficacy and was well tolerated through Wk 24 in patients with very limited treatment options due to resistance to approved ARV agents.