After hitting the mark in a phase 2 of its investigational islatravir paired with Gilead Sciences' lenacapivir, Merck & Co.'s islatravir is making further strides as a combination treatment with another Merck HIV drug for patients with virologically suppressed HIV-1.
The company evaluated a daily dose of islatravir combined with doravirine (brand name Pifeltro) in two phase 3 studies enrolling patients who either use baseline antiretroviral therapy (bART) or Gilead’s top-selling Biktarvy to achieve viral suppression. Both studies met the primary efficacy goal of HIV-1 RNA levels less than 50 copies/mL, an indicator of HIV viral load, and the combination proved non-inferior to bART and Biktarvy in those who switched to Merck’s treatment.
However, the superiority criteria were not met in the double-blind Biktarvy study. The bART phase 3 study was an open-label trial.
“We are encouraged by the results from these phase 3 trials evaluating a once-daily, oral, two-drug, single-tablet regimen of doravirine and islatravir,” Merck Chief Medical Officer Eliav Barr, M.D., said in a Dec. 19 press release. “We are committed to advancing our clinical programs for islatravir in combination with other antiretrovirals as potential options to help address the needs of people living with HIV.”
Merck will present more detailed findings at a future scientific congress and plans to file the data with regulatory agencies.
The company’s doravirine was approved in 2018 as a single-agent treatment and in combination with other GSK and Gilead meds in a regimen branded as Delstrigo. The latter treatment carries a boxed warning for the risk of worsening hepatitis B infections.
Islatravir is a nucleoside reverse transcriptase translocation inhibitor that is being studied in multiple early and late-stage combination trials. In October, Merck and Gilead reported that a once-weekly combo of islatravir and lenacapivir (Sunlenca) sustained suppression of the virus out to 48 weeks.
Those results followed up on Week 24 data that found 98% of patients kept their HIV-1 RNA below 50 copies/mL with once-weekly dosing. The partners continue to assess that combination in two phase 3 studies.
Merck revived its islatravir/lenacapivir studies in 2023 after the FDA lifted a previous hold on the study tied to a related islatravir trial. The HIV prospect is part of Merck’s vision for a successful post-Keytruda future after exclusivity runs out on the company’s oncology powerhouse in 2028. Gilead, meanwhile, is pushing lenacapivir forward as a potentially game-changing long-acting pre-exposure prophylaxis option.