Merck & Co. has reported another phase 3 win for islatravir in HIV, advancing its efforts to establish the near-approval molecule as a new anchor treatment for the infectious disease.
Integrase strand transfer inhibitors (INSTIs) are the backbone of current antiretroviral therapy regimens. Yet, while molecules such as Gilead Sciences' bictegravir have cut the risk of resistance, the potential for HIV to mutate to nullify INSTIs remains a problem. Equally, drug-drug interactions, cardiometabolic toxicities and other tolerability issues associated with INSTIs are a concern for some patients.
Merck is positioning islatravir as an alternative backbone for HIV drug regimens. Fresh from phase 3 wins in trials that switched patients on existing regimens to an islatravir-based treatment, Merck has reported a victory for its nucleoside reverse transcriptase translocation inhibitor in treatment-naive adults.
The latest phase 3 results come from a trial that compared a combination of doravirine and islatravir (DOR/ISL) to Gilead’s three-drug, INSTI-based treatment Biktarvy. After 48 weeks of once-daily dosing, the two arms had similar proportions of patients with HIV-1 RNA levels below a certain threshold. The result caused the trial to hit its primary noninferiority endpoint.
With the trial also finding the investigational combination had a comparable safety profile to that of Biktarvy, Merck is planning to submit applications including the data to health authorities. The FDA is already reviewing a filing for approval of DOR/ISL for the treatment of HIV-1 infection in adults to replace their current antiretroviral regimen. Merck is set to receive a decision from the FDA by April 28, 2026.
At an HIV investor event in July, Liz Rhee, M.D., vice president of clinical research infectious disease at Merck, said the treatment-naive data could support a label expansion in the U.S. and an initial approval application in the EU.
Merck executives primarily discussed DOR/ISL as an option for the 1 in 5 patients who switch HIV regimens each year, reflecting their belief that its convenience, tolerability and low risk of drug-drug interactions will make it a go-to choice. Eliav Barr, M.D., Merck Research Laboratories’ chief medical officer, also said islatravir regimens could enable physicians to reserve INSTIs for later-line use if needed.
With other trials evaluating weekly islatravir-based combinations, Merck has identified a $5 billion-plus opportunity for its late-stage HIV portfolio. Merck executives have argued that analysts underappreciate the HIV portfolio, creating an opportunity for the drugmaker to exceed expectations and partly offset threats to Keytruda if it hits its sales targets.