The experimental antiretroviral ibalizumab continues to effectively lower viral load in people with drug-resistant HIV through 48 weeks of treatment, according to study data presented at IDWeek 2017 in San Diego on Oct. 6.
The 48-week data on ibalizumab, a monoclonal antibody, are a follow-up to 24-week findings that were announced five months ago at the annual CROI conference. In that study, called TMB-301, HIV treatment-experienced study volunteers with multidrug-resistant virus were given a "loading dose" of 2,000 mg of ibalizumab, followed by 800 mg administered once every two weeks on top of an optimized background regimen. According to the 24-week results, patients with drug-resistant strains of HIV had a better chance of achieving viral suppression when ibalizumab was added to an existing regimen.
At the end of TMB-301, "all the patients that completed their 24-week endpoint in the Phase III study were enrolled in TMB-311, which is the expanded access," said Brinda Emu, M.D., an assistant professor of medicine in infectious diseases at the Yale School of Medicine, who presented the 48-week results at IDWeek.
Of the 31 people who completed TMB-301, all 27 in the U.S. enrolled in the expanded access program, continuing to receive 800 mg of ibalizumab every two weeks for an additional 24 weeks. Of the patients who enrolled in the expanded access program, 59% had exhausted more than three antiretroviral drug classes and 33% more than four; 15% (four patients) had resistance to all U.S. Food and Drug Administration (FDA)-approved antiretrovirals.
Despite these daunting baseline resistance numbers, "Potent viral load suppression [was] sustained through week 48," said Emu. Specifically, medial viral load reduction from baseline was 2.5 logs at week 24 and 2.8 logs at week 48, according to Emu.
Meanwhile, at week 48, 16 of the 27 volunteers had a viral load that was less than 50 copies/mL, and CD4 counts were maintained from baseline to week 48, Emu said.
Further, all patients who had achieved a viral load of less than 50 copies/mL by week 24 continued to see viral suppression at week 48.
Twenty-four of the 27 volunteers completed the 48-week study; all three withdrawals were determined to be for reasons unrelated to the study drug, according to Emu. Treatment-related adverse events were mild to moderate, but the most frequent side effects were upper respiratory tract infection (15%), diarrhea (11%), and rashes (7%).
Notably, said Emu, none of the patients developed anti-ibalizumab antibodies by week 48.
Ibalizumab has already been submitted for FDA approval, with an expected approval decision in January 2018. In June 2017, after the Phase 3 CROI data was announced, the FDA granted ibalizumab priority review.
"It is the first novel [mechanism of action] to be presented to the FDA since the integrase inhibitor class more than a decade ago," said Emu.
Study volunteers who wished to continue ibalizumab treatment are being given the option do so as part of the ongoing study until the drug is either approved or rejected by the FDA, according to Emu.