The first-in-class antiretroviral therapy islatravir (Merck) was well tolerated and had promising efficacy in a phase 2B study including treatment-naive adults with HIV-1 infection, supporting plans to initiate a phase 3 trial, an investigator said at the International AIDS Society Conference on HIV Science.
The proportion of patients achieving viral suppression at week 48 with combinations including the nucleoside transcriptase translocation inhibitor (NRTTI) was comparable to what was achieved with a standard triple regimen, said investigator Jean-Michel Molina, MD, professor of infectious diseases at the University of Paris Diderot, and head of the infectious diseases department at the Saint-Louis Hospital in Paris
The treatment was effective not only as part of a three-drug combination of islatravir, doravirine, and lamivudine over 24 weeks, but also over an additional 24 weeks in patients who achieved viral suppression and were switched to dual therapy with islatravir and doravirine, according to Dr. Molina.
“These are promising data that will encourage the company to move to a phase 3 trial to see how these results can be confirmed in a larger study set, and also to assess the potency of the dual combination for maintenance therapy in the future, providing also novel options for people with a drug that has a high genetic barrier to resistance and efficacy that seems to be quite interesting,” Dr. Molina said in an IAS press conference in Mexico City.
This drug has very potent activity not only against wild-type HIV-1 viruses, but also multiresistant viruses, according to Dr. Molina.
“It has a high inhibitory quotient at a very low dose, so you give people a tiny amount of drug – in the range of 1 milligram per day, instead of a few hundred milligrams with other, regular drugs,” he said.
Another attribute of islatravir is its long half-life of approximately 120 hours, allowing not only for once-daily dosing, but potentially for evaluation as once-weekly or once-monthly dosing in the future, he said, adding that a subdermal islatravir-eluting implant under investigation for preexposure prophylaxis has potential as a once-yearly option.
The international, multicenter, 121-patient clinical trial that Dr. Molina described included adults with HIV-1 infection naive to antiretroviral therapy randomized to islatravir (in one of three doses) plus doravirine and lamivudine, or to the combination of doravirine, lamivudine, and tenofovir (Delstrigo, Merck).
After at least 24 weeks of treatment, subjects in the islatravir treatment groups were transitioned to the two-drug combination of islatravir and doravirine if they had HIV-1 RNA levels less than 50 copies/mL and did not meet any protocol-defined criteria for virologic failure.
Those participants in the islatravir arms who received 48 weeks of treatment had “very good response” and safety that was comparable to the control arm, according to Dr. Molina.
At 48 weeks, the proportion of patients with HIV-1 RNA less than 50 copies/mL were 89.7%, 90%, and 77.4% for regimens containing islatravir 0.25 mg, 0.75 mg, and 2.25 mg, respectively, and 83.9% for those receiving the standard triple therapy, according to reported data.
All patients with protocol-defined virologic failure (greater than or equal to 50 copies/mL) in the study actually had very low viral load, below 80 copies/mL, Dr. Molina said.
The study was supported by Merck. Dr. Molina has been on the Merck advisory board and speaker’s bureau.
SOURCE: Molina J-M et al. IAS 2019, Abstract .