This article is more than 5 years old. Information may no longer be current.
Ibalizumab: A new treatment option for MDR HIV-1
Click Here to Manage Email Alerts
HIV is an infection for which many treatment advancements have been made over the past 3 decades. For many patients with HIV, treatment involves just a once-daily pill as an effective regimen for viral suppression with minimal side effects. For others, it is not that simple. Lack of adherence can lead to viral resistance, necessitating the use of less tolerable, more complex regimens.
For those who have tried numerous other regimens and have multidrug-resistant (MDR) HIV, a new type of antiretroviral medication for adults exists. In March 2018, the FDA granted approval to TaiMed Biologics for the first biologic agent targeted at HIV, log10 ibalizumab (Trogarzo).
Pharmacology
Ibalizumab is a monoclonal antibody indicated for use with other antiretroviral agents. Ibalizumab is directed to domain 2 of CD4+ Tcells, blocking HIV-1 from entering the cell by interfering with post-attachment steps. The specificity of its binding allows it to block viral entry into host cells without causing immunosuppression. Ibalizumab is active against MDR HIV-1, and studies have not detected cross-resistance with other agents. Ibalizumab is administered as a single 2,000-mg IV dose, followed by 800 mg IV every 2 weeks. The loading dose is administered over at least 30 minutes with a 60-minute observation period. If no infusion reaction occurs, subsequent doses can be administered over 15 minutes with a 15-minute observation period. Ibalizumab does not undergo significant metabolism, nor does it have significant drug-drug interactions.
Clinical trials
Ibalizumab was evaluated in a single-arm, open-label study in combination with an optimized background regimen (OBR) in highly treatment-experienced patients with MDR HIV-1 (TMB-301). Patients were either on no therapy or a failing regimen when they enrolled in the study. They received a loading dose of 2,000 mg IV, followed by 800 mg IV every other week for 24 weeks. One week after the loading dose, OBR was added with at least one additional susceptible agent.
The primary endpoint was the number of patients who experienced at least a 0.5 log10 drop in plasma HIV-1 RNA 1 week after starting ibalizumab alone. Secondary endpoints included the number of patients with plasma HIV-1 RNA levels of less than 50 and 200 copies/mL, and the mean change from baseline CD4 count at week 24.
Forty patients were enrolled in the study, with a mean age of 51 years; 15% were female and 45% were nonwhite. The mean duration of HIV infection was 21 years. The median baseline viral load was 4.6 log10 (18% had baseline viral load 100,000 copies/mL), and the median baseline CD4+ T-cell count was 73 cells/µL. Resistance testing showed that 53% and 35% of patients had exhausted at least three and four antiretroviral classes of drugs, respectively. Additionally, 16% of patients had pan-resistant HIV-1. One week after the loading dose of ibalizumab, 83% of participants experienced at least a 0.5 log10 drop in plasma HIV-1 RNA. At week 24, the mean change from baseline viral load was –1.6 log10, with 55% and 48% of patients having more than a 1 log10 and at least a 2 log10 reduction, respectively. There were 43% and 50% of patients who achieved a viral load of less than 50 and less than 200 HIV RNA copies/mL, respectively.
Of the 31 patients who completed TMB-301, 27 enrolled in the observational study, TMB-311, in which they continued to receive 800 mg IV every other week for a combined duration of 48 weeks. Of the 27 patients enrolled, 24 completed therapy through week 48. The three patients who discontinued treatment early did not do so because of ibalizumab. Viral suppression was maintained through week 48. Of the 27 patients, 16 (59%) had a viral load of less than 50 copies/mL and 17 (63%) had a viral load of less than 200 copies/mL. All 15 patients with a viral load of less than 50 copies/mL at week 24 maintained viral suppression to week 48.
Safety and tolerability
Ibalizumab appears to be well-tolerated. The most commonly reported side effects were mild and included headache, diarrhea and rash. In TMB-301 and TMB 311, most side effects were mild to moderate. In TMB-301, 17 serious adverse events were reported among nine patients; however, just one of these events was considered drug related (immune reconstitution inflammatory syndrome). In TMB-311, no new or unexpected safety concerns emerged.
Conclusion
For patients with MDR HIV-1 who have tried and failed other regimens, there is now a new option. Ibalizumab is the first monoclonal antibody approved by the FDA for the treatment of HIV-1 in combination with other antiretrovirals. It exerts its effect by blocking the HIV virus from entering the CD4 cell after attachment. The drug is administered as an IV infusion every other week. Although studies to date have been small, ibalizumab has demonstrated both safety and efficacy for heavily treatment-experienced adults with MDR HIV-1 infection.
- References:
- Emu B, et al. Open Forum Infect Dis. 2017;doi:10.1093/ofid/ofx162.093.
- Kuritzkes DR, et al. J Infect Dis. 2004;doi:10.1086/380802.
- Lalezari J, et al. Open Forum Infect Dis. 2016;doi:10.1093/ofid/ofw195.06.
- Lewis S, et al. Abstract 449LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.
- Trogarzo (ibalizumab) [package insert]. Irvine, CA: TaiMed Biologics USA Corp; 2018.
- Weinheimer S, et al. Abstract 4685. Presented at: International AIDS Society Meeting; July 23-26, 2017; Paris.
- For more information:
- Kati Shihadeh, PharmD, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.
Disclosure: Shihadeh reports no relevant financial disclosures.