General Information

Trogarzo (ibalizumab-uiyk) is a CD4-directed post-attachment HIV-1 inhibitor.

Trogarzo is specifically indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.

Trogarzo is supplied as an injection for intravenous administration. Trogarzo is administered as a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks after dilution in 250 mL of 0.9% Sodium Chloride Injection, USP.

Mechanism of Action

Trogarzo (Ibalizumab-uiyk) is a recombinant humanized monoclonal antibody, blocks HIV-1 from infecting CD4+ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for the entry of HIV-1 virus particles into host cells and preventing the viral transmission that occurs via cell-cell fusion.

Clinical Trial Results

The FDA approval of Trogarzo was based on trial TMB-301, a single arm, multicenter clinical trial conducted in 40 heavily treatment-experienced HIV-infected subjects with multidrug resistant HIV-1. Subjects were required to have a viral load greater than 1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications (NRTI, NNRTI, and PI) as measured by resistance testing. Subjects must have been treated with antiretrovirals for at least 6 months and be failing or had recently failed (i.e., in the last 8 weeks) therapy. The trial was composed of three periods: Control period (Day 0 to Day 6): This was an observational period to establish baseline HIV viral load. Functional monotherapy period (Day 7 to Day 13): All subjects received a 2,000 mg loading dose of Trogarzo on Day 7. Subjects on a failing ART regimen continued to receive their failing regimen in addition to the loading dose of Trogarzo.This period was to establish the virologic activity of Trogarzo. Maintenance period (Day 14 to Week 25): On Day 14 of the treatment period, viral load was assessed for the primary endpoint, and thereafter the background regimen was optimized to include at least one drug to which the subject’s virus was susceptible. The use of an investigational drug(s) as a component of the optimized background regimen was allowed. Beginning at Day 21, an 800 mg maintenance dose of Trogarzo was administered every two weeks through Week 25. This period was to establish the safety and durability of virologic suppression of Trogarzo when used in combination with an optimized background regimen. The primary efficacy endpoint was the proportion of subjects achieving a ≥ 0.5 log10 decrease in viral load from the beginning to the end of the “Functional monotherapy period” as compared to the proportion of subjects achieving a ≥ 0.5 log10 decrease from the beginning to the end of the “Control period”. At the end of the Control Period 3% of subjects achieved a ≥ 0.5 log10 decrease in viral load. At the end of the Functional monotherapy period 83% of subjects achieved a ≥ 0.5 log10 decrease in viral load. In addition, at Week 25, viral load <50 and <200 HIV-1 RNA copies/mL was achieved in 43% and 50% of subjects, respectively. Fifty-five percent of subjects had a ≥ 1 log10 reduction in viral load, and 48% of subjects had a ≥ 2 log10 reduction in viral load at Week 25. An increase in the mean and median number of CD4+ T-cells (44 cells/mm3 and 17 cells/mm3, respectively) was observed from Baseline to Week 25.