Trogarzo (ibalizumab), a long-acting monoclonal antibody infusion, suppressed HIV for up to 9.5 years in people with extensive prior treatment experience and highly resistant viruses, according to a report this week at the virtual IDWeek conference.
Although only a small number of people used Trogarzo for that long, these findings show that it can be an effective component of long-term antiretroviral therapy for people with few remaining treatment options, the researchers concluded.
Trogarzo is a monoclonal antibody administered via intravenous infusion once every two weeks, making it the first antiretroviral that does not require a daily dose. Instead of directly targeting HIV, it attaches to the CD4 receptor on T cells and interferes with a protein shape change that allows the virus to enter. Theratechnologies, the company that developed the drug, calls it a post-attachment HIV inhibitor.
The Food and Drug Administration approved Trogarzo in 2018 for people with HIV who have limited treatment options because they have tried numerous previous therapies and have developed multidrug-resistant viruses.
The approval was based on results from the Phase III TMB-301 trial, which enrolled people on a failed regimen who were resistant to three or more classes of antiretrovirals but had at least one fully active drug available to build an optimized baseline regimen. First, they added Trogarzo to their failing regimen. Then, after seven days, their treatment was optimized based on resistance testing. As reported at IDWeek 2016 , 43% had an undetectable viral load (below 50) after 24 weeks of treatment.
For the current analysis, researchers analyzed long-term outcomes among people with multidrug-resistant HIV in a previous phase IIb trial (TMB-202), which was conducted from October 2008 to January 2011. Participants were randomly assigned to receive Trogarzo at a dose of either 800 milligrams every two weeks or 2000 mg every four weeks plus an optimized background regimen for 24 weeks.
Of the 113 people in that study, 56 were transferred to a new drug investigation protocol after the trial ended. Twelve of them, along with the participants from the Phase III trial, were subsequently enrolled in an expanded access program (TMB-311) and remained on treatment with continuous monitoring until Trogarzo became commercially available in March 2018.
The 12 long-term participants were all men, and all but one were white. When they enrolled in TMB-202, the average age was 55 years, more than 80% were over 50, and they had been living with HIV for a median of 22 years. At the start of that study, the mean viral load was approximately 25,000 copies, the mean CD4 count was 135, and a quarter had a count below 50, indicating advanced immunosuppression. Five had been randomly assigned to the 800 mg dose of Trogarzo, and seven received the 2000 mg dose.
At the end of TMB-202, eight of the 12 had an undetectable viral load (less than 50) and all but one met the study's definition of viral suppression (less than 200). At the final follow-up visit of TMB-311, which took place between 7.8 and 9.5 years after initial enrollment in TMB-202, 11 had a viral load below 50 and all 12 were below 200.
Eight participants maintained viral suppression without additional antiretrovirals, including two who were able to simplify their treatment. The other four required additional medications, but in two of these cases, the only change was the addition of a ritonavir booster.
The treatment also led to immune recovery. By the end of TMB-202, participants had gained an average of 64 CD4 cells, and by week 96 of TMB-311, the average gain had increased to 99 cells.
Trogarzo was generally safe and well tolerated. No one withdrew from TMB-311 or was lost to follow-up. Half of the participants experienced serious adverse events, but none were considered related to Trogarzo. There were two deaths from unrelated causes.
"In treatment-experienced patients with limited options, these data demonstrate the durability of viral suppression when the long-acting antiretroviral ibalizumab is combined with short-acting oral agents," the researchers concluded.
From: https://www.poz.com/article/trogarzo-maintains-viral-load-suppression-nearly-10-years