In March, the FDA approved ibalizumab-uiyk (Trogarzo; TaiMed Biologics USA Corp.) for use in combination with other antiretroviral agents in adult patients with multi-drug-resistant human immunodeficiency virus 1 (HIV-1) who have previously received multiple antiretroviral therapies and who are on a regimen that is unable to suppress viral load. Ibalizumab-uiyk is a recombinant humanized monoclonal antibody. It binds to CD4 cells and interferes with the post-attachment processes that allow entry of HIV-1 virus into a host cell. CD4-directed post-attachment HIV-1 inhibitors are a new class of antiretroviral drug therapy that offer a new option for patients with multi-drug-resistant HIV-1 infection.
Efficacy of ibalizumab-uiyk was established in a single-arm multicenter trial (TMB-301) of 40 participants.1 All participants have heavy treatment experience, a viral load greater than 1,000 copies/mL, and documented resistance to a minimum of one antiretroviral drug from each of the following three classes: nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI).
For inclusion in the trial, participants received therapy for at least six months and were currently failing therapy or had failed within the last eight weeks. Throughout the trial, a participant’s baseline antiretroviral therapy was continued. The first week of the trial served as a screening period to establish baseline viral loads (control period). On day seven, all participants received a 2,000 mg infusion of ibalizumab-uiyk and were monitored through day 13. This “functional monotherapy period” was used to determine virologic activity of ibalizumab-uiyk.
A maintenance period that spanned from day 14 through week 25 assessed viral load changes. During the maintenance period, a participant’s background regimen was optimized to ensure viral susceptibility to at least one drug. Participants received 800mg of ibalizumab-uiyk every two weeks starting day 21 through week 25 of the trial. Within one week of initiating ibalizumab-uiyk therapy, 83% of participants demonstrated a significant decrease in viral load. At the conclusion of the study period, 43% of participants achieved HIV RNA suppression (HIV RNA <50 copies/mL). Studies have not demonstrated cross resistance between ibalizumab-uiyk and other antiretroviral therapies. A decrease in susceptibility to ibalizumab-uiyk therapy after multiple administrations of the drug have been observed. The development of cross-resistance to other classes of therapy has not been observed in cell culture studies.
Experience with ibalizumab-uiyk is limited. A total of 292 patients infected with HIV-1 have been exposed to ibalizumab-uiyk. The most common adverse reactions in TMB-301 were mild to moderate in severity and included: diarrhea (8%), dizziness (8%), nausea (5%), and rash (5%). As with all combination antiretroviral therapies, use of ibalizumab-uiyk can result in immune reconstitution inflammatory syndrome (IRIS), which occurred in one participant in the TMB-301 trial. There is insufficient data to assess differences in adverse effects by sex, race, or age. Ibalizumab-uiyk is a monoclonal antibody and would cross the placenta during pregnancy.
Ibalizumab-uiyk therapy is administered intravenously every two weeks. Therapy is initiated with a 2,000 mg loading dose and maintained with 800 mg doses administered every two weeks. Dosing modifications due to renal, hepatic, or concomitant therapies are not studied. Modifications are not anticipated to be required for renal impairment or drug interactions. Ibalizumab-uiyk is administered intravenously over 15 to 30 minutes in a clinical setting. All patients must be monitored for one hour after the first dose is administered. If no reaction has occurred, the patient may be monitored for 15 minutes after administration of subsequent doses.1
1. Trogarzo [package insert]. Irvine, CA: TaiMed Biologics USA Corp. March 2018.