Gilead and MSD’s once-weekly HIV pill meets primary endpoints in Phase III trials
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A transformative once-weekly HIV treatment combining islatravir and lenacapavir proved statistically non-inferior to daily standard-of-care antiretroviral therapies in Phase 3 ISLEND trials, paving the way for global regulatory submissions by Gilead and MSD.
Gilead and MSD will be filing the data from the Phase III trials of the once-weekly HIV pill to regulatory authorities. Gilead Sciences and MSD’s human immunodeficiency virus (HIV) once weekly tablet combination has met primary endpoints in two Phase III trials.
The ISLEND-1 and ISLEND-2 Trials
In the 48-week ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299) trials, the two pharmaceutical companies investigated the single-tablet HIV treatment regimen of islatravir/lenacapavir (ISL/LEN) in patients with HIV who are virologically suppressed, switched from Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) (ISLEND-1) or daily standard of care (SoC) antiretroviral regimens (ISLEND-2).
The primary efficacy endpoint of ISLEND-1 and ISLEND-2 was the percentage of participants with HIV-1 RNA levels ≥50 copies/mL at week 48. In the double-blind ISLEND-1 trial, the once-weekly, single-tablet regimen of ISL/LEN was found to be statistically non-inferior to Biktarvy. In the open-label ISLEND-2 trial, ISL/LEN was found to be statistically non-inferior to SoC daily oral antiretroviral therapy regimens.
The safety profile of ISL/LEN was generally comparable to BIKTARVY in ISLEND-1 and to SoC antiretroviral regimens in ISLEND-2. Based on the study, Gilead and MSD plan to file the data from the ISLEND trials with regulatory authorities globally and submit the detailed findings for presentation at a future scientific congress.
Transformational Innovation in HIV Care
Dr Jared Baeten, SVP, clinical development and virology therapeutic area head, Gilead Sciences, said: “Long-acting oral therapies represent a new wave of transformational innovation in HIV drug development, with the potential to reshape the landscape of care. Innovative oral HIV treatment options that allow for less frequent dosing may make a meaningful difference in the lives of people living with the virus, potentially offering more flexibility and discretion”.
Dr Eliav Barr, SVP, head of global clinical development and chief medical officer at MSD Research Laboratories, added: “By advancing this investigational novel once-weekly oral regimen of ISL/LEN, we aim to bring forward a new long-acting oral option that, if approved, would represent the first of its kind with less frequent dosing and further expand options for people living with HIV.”
The combination of ISL/LEN targets multiple stages of HIV-1 replication, potentially offering people with virologically suppressed HIV a novel, long-acting oral single-tablet regimen. The potency and pharmacokinetic profiles of ISL/LEN enable long-acting dosing as a once-weekly tablet for HIV treatment, if approved. In an open-label Phase II study (NCT05052996), 88.5% and 100% of adults treated with the once-weekly treatment of ISL/LEN maintained undetectable viral load (HIV-1 RNA <50 copies/mL) at week 96.
Gilead’s Growth in the PrEP Market
Gilead has also cemented its name in the prevention space with its twice-yearly pre-exposure prophylaxis (PrEP) version of lenacapavir, known under the brand name Yeztugo in the US. Data show that 99.9% of participants who received Yeztugo in the Phase III PURPOSE 1 and PURPOSE 2 trials remained HIV negative. The PrEP treatment gained approval from the US Food and Drug Administration (FDA) in June 2025.
While there have been concerns about price being a barrier to entry for patients, Gilead has allowed generic development of the therapy in third-world countries to help reduce this barrier. Gilead is also investigating a once-yearly version of the PrEP therapy. Lenecapavir is also approved for use as an HIV treatment, under the brand name Sunlenca. The drug is used as part of a combination with other ARTs.
GlobalData predicts a combined patient-based sales forecast for Yeztugo and Sulenca of $4.98bn in 2033. The HIV market across the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan) is forecast to grow at a compound annual growth rate (CAGR) of 1.9% from $26.5bn in 2023 to $32.1bn in 2033, according to GlobalData.
