Merck's experimental HIV drug islatravir hits with a PhIII combo win and FDA filing plans
Back in March, Merck and Gilead agreed to a partnership to challenge GlaxoSmithKline on long-acting HIV meds — by combining one drug from both Merck and Gilead that had shown potential. While Gilead brought its capsid inhibitor lenacapavir, Merck brought islatravir into the deal — a small molecule that the pharma acquired in 2012 from a small Japanese firm.
While that partnership is ongoing, islatravir is coming out of 2 Phase III pivotal trials with back-to-back successes and plans to beat a quick advance to the FDA.
The pharma giant revealed top-line results this morning from its pivotal Phase III trials of a once-daily oral pill combining Merck’s FDA-approved anti-HIV treatment Pifeltro with islatravir. The participants, who are adults with HIV-1 infection who are on two different antiretroviral therapy protocols, including a bictegravir/emtricitabine/tenofovir triple, were compared at 48 weeks.
Merck has maintained a steady runner-up rep in HIV, a field dominated by Gilead and then ViiV, majority owned by GSK. And no matter what happens with the Merck combo now that it’s headed to regulators, analysts don’t expect anything to beat out Gilead’s market leader. A few months ago Bernstein’s Ronny Gal assessed the alliance between Merck and Gilead, concluding:
For HIV treatment it will be hard to unseat Biktarvy. HIV treatments have effectively reached the upper-limit on efficacy and tolerability. From here, new products will try to differentiate based on quality-of-life enhancements like less frequent dosing and lower associated weight gain. These value propositions are real, but patient turnover in HIV is relatively low and we believe it would a tough sell to switch virally suppressed patients of Biktarvy. As a result, we model only 30% peak market share for ISL/LEN combinations – material, but less than Biktarvy.
Both of the Merck trials met their primary endpoint on the percentage of participants with HIV-1 RNA levels at or below 50 copies/mL — showing that antiviral efficacy was comparable between the drug combo and antiretroviral therapies, according to a company statement.
For reference, any level of HIV-1 RNA below 50 copies/mL is considered optimal for patients — sometimes that number is considered undetectable in a blood test. A “lower viral load” is any number below 10,000 copies/mL — and a high viral load is considered to be anywhere from 100,000 to a million copies of RNA/per mL of blood.
The safety and tolerability of the combination drug were consistent with data from Phase II studies, according to Merck — and these results will lead the way for “global regulatory applications.”
“We are encouraged by the results from the Phase 3 ILLUMINATE SWITCH A and B trials, in which the DOR/ISL dual regimen efficacy was comparable to certain commonly used three-drug regimens,” said Joan Butterton, VP of global clinical development, infectious diseases at Merck Research Laboratories. “We will continue to study doravirine/islatravir in diverse populations of people living with HIV and look forward to sharing data from these trials.”