Gilead, Merck present pivotal Phase 3 Islend data for first once-weekly oral HIV regimen

BRAZIL—Detailed phase 3 results suggest that a once-weekly pill combining Gilead Sciences’ lenacapavir and Merck & Co.’s islatravir could become the first complete weekly oral treatment for HIV.

Data from the two Islend phase 3 trials showed that the single-tablet combination of islatravir and lenacapavir (ISL/LEN) maintained HIV viral suppression as effectively as daily oral regimens, including Gilead’s Biktarvy.

Researchers presented the findings at the 26th International AIDS Conference in Rio de Janeiro, Brazil.

Gilead’s clinical development lead in virology, Jared Baeten, said the weekly treatment could help address adherence challenges among people living with HIV by reducing the burden of taking medication every day.

In Islend-1, 607 participants who had already achieved viral suppression with Biktarvy switched to ISL/LEN or continued their existing treatment.

After 48 weeks, none of those receiving ISL/LEN had HIV RNA levels of at least 50 copies/mL, compared with one patient (0.3%) in the Biktarvy group.

CD4+ T-cell counts fell by an average of 10 cells/μL in the ISL/LEN group and 18 cells/μL among Biktarvy users.

Participants entered the study with average CD4 counts of about 740 cells/μL.

Meanwhile, Islend-2 enrolled 626 people who had achieved viral suppression using various daily regimens.

At Week 48, one ISL/LEN recipient (0.3%) and four patients (1.3%) receiving standard daily treatment had HIV RNA levels of at least 50 copies/mL.

Average CD4 counts declined by 45 cells/μL among ISL/LEN recipients and eight cells/μL in the daily treatment group.

Researchers noted that the ISL/LEN group had higher baseline CD4 counts, with the two groups converging by Week 48.

Safety profile remains comparable

The weekly combination was generally well tolerated in both trials.

Treatment-emergent adverse events occurred in the high-70% range across study groups, while treatment-related adverse events remained relatively low.

In Islend-1, treatment-related adverse events occurred in 13.5% of ISL/LEN recipients and 13.2% of Biktarvy users. In Islend-2, the rates were 18.5% and 0.3%, respectively.

The FDA previously placed several Merck islatravir studies on clinical hold in 2021 after patients experienced declines in lymphocyte and CD4+ T-cell counts.

However, Baeten said the earlier safety signal involved islatravir doses substantially higher than those used in the Islend trials. Researchers reported no meaningful differences in lymphocyte counts between treatment groups at Week 48.

Gilead advances long-acting HIV prevention

Gilead is also expanding lenacapavir’s role in HIV prevention.

The company markets the twice-yearly injectable PrEP under the brand name Yeztugo, which generated $166 million in sales during the first quarter.

In updated Purpose trial results, 95% of eligible participants in Purpose 1 chose to start or continue Yeztugo during the open-label extension, with no HIV infections reported among them during 52 weeks of follow-up.

In Purpose 2, 95% of participants also opted for Yeztugo, although one HIV infection occurred despite timely injections.

Meanwhile, Merck is developing alimatravir (MK-8527), a potential once-monthly oral PrEP option, and is studying islatravir with the NNRTI ulonivirine as a possible weekly oral HIV treatment.