By: Karen Chen, PharmD Candidate c/o 2019
Ibalizumab-uiyk (Trogarzo®) is specifically indicated for the treatment of human immunodeficiency virus type- 1 (HIV-1) infection in combination with other antiretroviral medications in heavily-treatment experienced adults with multidrug resistant HIV-1 infections who are failing their current antiretroviral regimen. Ibalizumab-uiyk is a CD4- directed post-attachment HIV-1 inhibitor that was approved in March 2018 by the FDA.1 The human immunodeficiency virus is notorious for its ability to genetically mutate at a rapid rate and gain resistance to many of the current antiretroviral therapies on the market. Ibalizumab-uiyk is the first drug in a new class of antiretroviral medications that is approved for multidrug resistant HIV.2
Ibalizumab-uiyk is a recombinant humanized monoclonal antibody that works to block HIV-1 virus from infecting CD4+ T cells by binding to domain 2 of CD4+ T cells and interfering with the post-attachment steps required for the entry of the HIV-1 viral particles into host cells.1,2 Unlike many of the current HIV-1 treatments available, ibalizumab-uiyk is an injection that is administered intravenously 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% of Sodium Chloride Injection, USP, by a trained medical professional.1
TMB-301 is a single-arm multicenter clinical trial in which 40 subjects, all of whom are heavily treatment-experienced HIV- infected patients, were given ibalizumab-uiyk for 24 weeks. These patients were required to have a viral load greater than 1,000 copies/mL despite being on antiretroviral therapy. Subjects were required to have been treated with antiretrovirals for at least 6 months and be failing or have recently failed therapy to be enrolled in this study. Subjects were also required to have documented resistance to at least one antiretroviral medication from each of the three classes of antiretroviral medications which include nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI), as measured by resistance testing to ensure they had multidrug resistant HIV-1 on a failing HIV treatment regimen.3 At baseline, 53% of the subjects had been treated with 10 or more antiretroviral drugs prior to trial enrollment. Of that 53% of subjects, 98% percent had been treated with NRTIs, 98% with PIs, 80% with NNRTIs, 78% with integrase strand transfer inhibitors (INSTIs), 30% with glycoprotein- 41 (GP41) fusion inhibitors, and 20% with C-C chemokine receptor type 5 (CCR5) co-receptor antagonists.1
Subjects underwent an observational period from Day 0 to Day 6, in which they continued their failing antiretroviral regimen and in which a baseline HIV viral load was established. On Day 7, all subjects continued to receive their failing antiretroviral regimen, in addition to receiving the 2,000 mg loading dose of ibalizumab-uiyk. On Day 14, viral load was assessed for the primary endpoint.2 The efficacy of ibalizumab-uiyk is measured by the number of HIV-1 viral load copies in the bloodstream from Day 7 to Day 14.4 On Day 21, subjects were administered the 800 mg maintenance dose of ibalizumab-uiyk every two weeks, concomitant with a susceptible antiretroviral medication, until Week 25. Ibalizumab-uiyk was used to optimize background regimen from Day 14 onward.2
Clinical trials have shown that at the end of Day 21, one week after ibalizumab-uiyk was added to subject’s current failing antiretroviral treatment, 83% of subjects achieved a ≥ 0.5 log10 decrease in viral load.2 At the end of the clinical trial (Week 25), in which ibalizumab-uiyk was administered in combination with another active antiretroviral medication, 43% of subjects had a viral load <50 copies/mL and 50% of subjects achieved <200 HIV-1 RNA copies/mL, indicating these subjects had achieved HIV RNA suppression.2,5 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.2
It is important to recognize some of the common adverse reactions of ibalizumab-uiyk. Representation of common adverse reactions including diarrhea, dizziness, nausea, and rash occurred in five percent or more of the subjects. One of a few severe side effects that pharmacists should counsel patients on and be aware of is immune reconstitution inflammatory syndrome (IRIS). IRIS occurs during the initial phase of treatment with ibalizumab-uiyk and with other combination antiretroviral therapies where the immune system of an HIV- infected patient may get stronger and begins to fight infections that were hidden. The immune system produces an inflammatory response to indolent or residual opportunistic infections, requiring more complicated treatment.1
HIV-1 infected patients who have multi-resistant HIV have limited treatment options. Without an effective and susceptible antiretroviral regimen on board, many of these patients are at risk for HIV- related complications and progression to AIDS. Ibalizumab-uiyk has shown clinical efficacy in those with multidrug resistant HIV-1 infections who are failing their current therapies and can improve outcomes in patients who may have run out of HIV treatment options.
- Trogarzo® (ibalizumab-uiyk) [package insert]. Irvine, CA; TaiMed Biologics, Inc.; Revised 03/2018.
- CenterWatch. Trogarzo® (ibalizumab-uiyk). https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100252/trogarzo-ibalizumab-uiyk. Accessed September 12, 2018.
- U.S. Food and Drug Administration. FDA approves new HIV treatment for patients who have limited treatment options. Updated 03/07/2018. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm599657.htm. Accessed 09/12/2018.
- U.S. Food and Drug Administration. Drug Trials Snapshots: TROGARZO. Updated 03/20/2018. https://www.fda.gov/Drugs/InformationOnDrugs/ucm601383.htm. Accessed 09/12/2018.
- Center for Disease Control and Prevention. HIV Treatment as Prevention. Updated 09/10/2018. https://www.cdc.gov/hiv/risk/art/index.html. Accessed 09/12/2018.