Novel Once-Weekly HIV Treatment with Islatravir and Lenacapavir Shows Promising 94% Viral Suppression at 48 Weeks

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The novel combination of islatravir (Merck) and lenacapavir (Gilead) maintained high rates of viral suppression in virologically suppressed adults with HIV after 48 weeks of treatment, according to the results of a Phase II clinical trial (NCT05052996) presented during at ID Week 2024.^1,2 Trial investigators noted that these findings could lead to the combination therapy becoming the first weekly oral HIV regimen.

“Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy,” said Elizabeth Rhee, MD, vice president, Global Clinical Development, Merck Research Laboratories. “We are pleased to see these encouraging 48-week data for this once-weekly oral combination regimen and advance to phase 3 clinical trials in collaboration with Gilead.”¹

Lenacapavir is a potential first-in-class, long-acting HIV-1 capsid inhibitor. The multi-stage mechanism of action for lenacapavir is distinguishable from currently approved antiviral drug classes and is intended to provide a new pathway for the development of long-acting treatments for individuals infected with or at risk for HIV-1.

The FDA granted lenacapavir with Breakthrough Therapy Designation in May 2019 to treat HIV infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs. Although most antiretroviral agents act on a single stage of viral replication, lenacapavir targets multiple stages of the HIV-1 lifecycle and has no known cross resistance to other existing drug classes, according to Gilead.³ Islatravir is a novel nucleoside reverse transcriptase translocation inhibitor currently being investigated in multiple ongoing early and late-stage clinical studies combined with other antiretroviral therapies for HIV-1.

The current trial is an open-label, active-controlled study that randomly assigned 104 virologically suppressed adults in a 1:1 ratio to receive oral islatravir 2 mg and lenacapavir 300 mg once weekly (n=52) or to remain on their daily oral regimen of Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets; n=52). Trial enrollees had a median age of 40 years, ranging from 20 to 76 years of age, with 18% assigned female gender at birth, 50% being non-white, and 29% being Latino.

At 48 weeks, participants administered the islatravir and lenacapavir combination maintained a high rate (n=49; 94.2%) of viral suppression, which was one of the trial’s secondary endpoints. Additionally, no participants had a viral load of ≥50 copies/mL after 48 weeks. Data from 24 weeks of treatment presented in March 2024 for the islatravir and lenacapavir combination also showed a 94.2% viral suppression rate.⁴

At 48 weeks, investigators observed comparable rates of HIV suppression among those who switched to once weekly islatravir and lenacapavir, at 94.2%, or who continued Biktarvy at 92.3%. There were no individuals in either cohort who had a viral load of ≥ 50 copies/mL after 48 weeks.

In terms of safety, treatment-related-adverse events (TRAEs) were reported by 19.2% of individuals administered islatravir and lenacapavir compared with 5.8% of individuals in the Biktarvy cohort. The most frequently reported TRAEs were dry mouth (3.8%) and nausea (3.8%). There were no grade 3 or 4 TRAEs related to the study drug reported by either cohort.

“The future of HIV treatment is person-centered, with long-acting options tailored to help meet the needs and preferences of people affected by HIV,” Jared Baeten, MD, PhD, senior vice president, Virology Therapeutic Area Head, Gilead Sciences, said in a press release. "There is no ‘one size fits all’ approach. The complexities of HIV care require putting people first in the development of biomedical innovations as we keep striving to offer options for all those living with HIV. These data presented at IDWeek demonstrate our commitment to continuous scientific discovery aimed at further transforming the HIV treatment landscape.”¹

References

1. Gilead and Merck Announce Phase 2 Data Showing a Treatment Switch to an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression in Adults at Week 48. News release. Gilead. October 19, 2024. Accessed October 21, 2024. https://www.gilead.com/news/news-details/2024/gilead-and-merck-announce-phase-2-data-showing-a-treatment-switch-to-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral-suppression-in-adu

2. Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV. ClinicalTrials.gov. Updated September 19, 2024. Accessed October 21, 2024. https://clinicaltrials.gov/study/NCT05052996

3. FDA Lifts Clinical Hold on Investigational Lenacapavir for the Treatment and Prevention of HIV. Gilead Sciences. News release. May 16, 2022. Accessed October 21, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2022/5/fda-lifts-clinical-hold-on-investigational-lenacapavir-for-the-treatment-and-prevention-of-hiv

4. Gilead and Merck Announce Phase 2 Data Showing an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression at Week 24. News release. March 6, 2024. Accessed October 21, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/3/gilead-and-merck-announce-phase-2-data-showing-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral