FOSTER CITY, Calif., and RAHWAY, N.J. — An investigational once-weekly oral HIV treatment developed by Gilead Sciences and Merck maintained viral suppression through 48 weeks in two Phase 3 trials, the companies announced.
The single-tablet regimen combines 2 mg of islatravir with 300 mg of lenacapavir. It was evaluated in adults whose HIV was already virologically suppressed and who switched from daily antiretroviral treatment.
Results from the ISLEND-1 and ISLEND-2 trials will be presented at the 26th International AIDS Conference. Gilead and Merck said the findings are expected to support future regulatory submissions.
In ISLEND-1, the once-weekly combination was noninferior to Gilead’s daily HIV treatment Biktarvy. At Week 48, none of the participants who switched to islatravir and lenacapavir had HIV-1 RNA levels of at least 50 copies per milliliter, compared with 0.3% of participants who remained on Biktarvy.
“Once-daily, combination, single-tablet antiretroviral therapy is the cornerstone of HIV treatment today. However, the treatment landscape is evolving,” said Jürgen Rockstroh of the Department of Medicine at University Hospital Bonn in Germany. “Long-acting therapies provide an alternative to daily pills. The ISLEND-1 study results show the potential of ISL/LEN as the first once-weekly oral single-tablet treatment option.”
Treatment-related adverse events were reported in 13.5% of participants receiving the investigational combination and 13.2% of those taking Biktarvy. The most common treatment-related adverse events were nausea and headache.
Serious adverse events occurred in 5.3% of participants receiving islatravir and lenacapavir and 4.6% of those receiving Biktarvy. Discontinuations due to adverse events were uncommon, and CD4-positive T-cell and lymphocyte counts remained stable in both groups.
In ISLEND-2, the once-weekly regimen was also noninferior to other daily standard-of-care HIV treatments. At Week 48, 0.3% of participants receiving islatravir and lenacapavir had HIV-1 RNA levels of at least 50 copies per milliliter, compared with 1.3% of those who continued their existing daily regimen.
“Single tablet regimens have transformed the outlook for millions of people living with HIV,” said Amy Colson, Research Director at Community Resource Initiative and Medical Director of the Zinberg Clinic at Cambridge Health Alliance. “Having a treatment option with once weekly dosing can expand choice to help address individual needs and preferences. The 48-week findings provide the evidence for ISL/LEN as the potential first once-weekly oral treatment option to help support long-term treatment needs and be responsive to the preferences of people living with HIV.”
Treatment-related adverse events were reported in 18% of participants receiving the investigational regimen and fewer than 1% of those remaining on standard-of-care treatment. The most common events in the islatravir and lenacapavir group were headache, nausea and diarrhea.
Participants who switched to the once-weekly treatment also reported higher treatment satisfaction and a lower treatment burden than those who remained on daily therapy.
Lenacapavir is a capsid inhibitor designed to disrupt HIV at several stages of its lifecycle. Islatravir is a nucleoside analog that blocks HIV-1 replication through multiple mechanisms involving reverse transcriptase.
The combination remains investigational and has not been approved for use.
