• 09 Mar 2024
• Admin
• News Article

Gilead and Merck Announce Phase 2 for Islatravir and Lenacapavir

Gilead and Merck announce results from phase 2 clinical study of combination regimen of islatravir and lenacapavir

Gilead Sciences, Inc. and Merck & Co, known as MSD outside of the US and Canada, announced results from the phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class capsid inhibitor. These late-breaking data were presented during an oral session at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). Prior to the late-breaker oral presentation, the key findings were featured in a CROI press conference.

About Trial

• At 24-week, the novel investigational combination maintained a high rate (94.2%) of viral suppression (HIV-1 RNA <50 copies/mL), which is a secondary endpoint of the study. 
• Results of the primary endpoint (HIV-1 RNA =50 copies/mL (c/mL) showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of >50 copies/mL at Week 24; the participant later suppressed on islatravir and lenacapavir at week-30.

Potential Dosing

• The potent antiviral activities, along with pharmacokinetic profiles of islatravir and lenacapavir, support their development as an investigational once-weekly oral combination regimen. 
• Single-tablet daily oral therapies have helped to transform HIV care, but options that allow for less frequent dosing have the potential to address adherence, stigma and other challenges faced by some individuals taking daily oral antiretroviral therapy.

Leader from Gilead Sciences

“HIV treatment is not one size fits all – developing once-weekly treatment options could help meet the needs of each individual, aiming toward maximizing long-term outcomes for people with HIV,” said Jared Baeten, vice president, HIV clinical development, Gilead Sciences. “These promising data presented at CROI help bring us one step closer to our goal of providing a wide range of options that may help transform the HIV treatment landscape.”

About NCT05052996

• In this open-label, active-controlled study (NCT05052996), virologically suppressed adults (n=104) on Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or to continue daily oral Biktarvy (n=52). The median age of participants was 40 years. 
• Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx.

Trial Results

• Results of the primary endpoint, measured as HIV-1 RNA =50 copies/mL (c/mL) at week-24 per US FDA Snapshot algorithm, showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of more than 50 copies/mL at week-24; the participant later suppressed on islatravir and lenacapavir at week-30. No participants in the Biktarvy group had a viral load of more than 50 copies/mL at week-24. 
• Results of the secondary endpoint, as measured by the proportion of individuals with HIV-1 RNA < 50 c/mL at week-24, showed that participants who switched to treatment with once-weekly islatravir and lenacapavir or continued Biktarvy both maintained comparable high rates of HIV suppression at week- 24 (94.2% v. 94.2%).

TRAEs

• Grade 1 and 2 treatment-related-adverse events (TRAEs) reported in the islatravir and lenacapavir group included dry mouth and nausea (each 3.8%). 
• No grade 1 and 2 TRAEs were reported in the Biktarvy group. 
• No grade 3 or 4 TRAEs related to study drug in either treatment group were reported. 
• Two participants discontinued islatravir and lenacapavir due to adverse events unrelated to the drug. 
• In addition, no differences were seen between treatment groups for changes in CD4+ T cell counts or absolute lymphocyte counts.

Words from Merck Research 

“Our strategies for managing and treating HIV must evolve with the needs of the HIV community and we are excited to have these promising first data from the phase 2 study for islatravir and lenacapavir presented at CROI,” said Dr. Elizabeth Rhee, vice president, global clinical development, Merck Research Laboratories. “Gilead and Merck remain committed to this collaboration and to the development of a potential once-weekly oral therapy for people living with HIV who may need additional options to help maintain viral suppression.”

The phase 2 study will continue in an open-label fashion through week-48. Longer-term data will be presented at a future scientific conference.

Islatravir: Alone or Combo

Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally. The safety and efficacy of the combination of islatravir and lenacapavir have not been established.

Lenacapavir Approvals Around the World

• Lenacapavir, marketed as Sunlenca, is approved in Australia, Canada, the European Union, Israel, Japan, Switzerland, the United Arab Emirates, the United Kingdom and the United States for the treatment of people with multi-drug resistant HIV in combination with other antiretroviral(s).
• Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation for the treatment of HIV-1 in combination with other antiretrovirals.

About Sunlenca

• Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor indicated for the treatment of HIV infection, in combination with other antiretroviral(s), in adults with multi-drug resistant HIV who are heavily treatment-experienced. 
• Sunlenca is the only HIV treatment option administered twice-yearly. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option.

Lenacapavir: MOA

• The multi-stage mechanism of action of Sunlenca’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. 
• While most antivirals act on just one stage of viral replication, Sunlenca is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes.

Lenacapavir

• Lenacapavir is being developed as a foundation for future HIV therapies developed by Gilead. The goal is to offer both long-acting oral and injectable options with various dosing frequencies in combination with other antiretroviral agents for treatment or as a single agent for prevention. 
• This approach aims to help address the individual needs and preferences of people with HIV and people who could benefit from pre-exposure prophylaxis (PrEP). 
• The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use has not been established.
• Lenacapavir is being evaluated as a potential long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research programme.