Lenacapavir Shows Efficacy as Long-Acting Agent in Combination Regimen For HIV

Lenacapavir (Sunlenca; Gilead Sciences, Inc.) combined with the investigational broadly neutralizing antibodies (bNAbs) teropavimab (GS-5423) and zinlirvimab (GS-2872) was well-tolerated for patients with HIV, according to the results from a phase 1b clinical trial presented at the 30th Conference on Retroviruses and Opportunistic Infections (CROI). After 6 months, 90% of patients experienced virologic suppression of HIV, the study found.

“Novel long-acting HIV treatment options will drive the next chapter in care and may help meet the therapy needs and preferences of people living with HIV. In this study we found that lenacapavir and bNAbs in a combination approach may have a significant role to play in the future treatment of HIV,” said Joseph Eron, MD, lead study investigator and the chief of the Division of Infectious Diseases at the University of North Carolina School of Medicine, in a press release.

Later this year, a phase 2 study will evaluate a regimen of lenacapavir with GS-5423 and GS-2872 for virologically suppressed patients with HIV (HIV-1 RNA <50 copies/mL) against different dose levels of GS-5423 and GS-2872. The endpoints will be safety and efficacy.

Lenacapavir functions by inhibiting the viral replication of HIV at multiple stages. Investigators hope it is offered as a long-acting, oral and injectable treatment available at different doses, combined with other antiretroviral agents, or as a monotherapy to prevent HIV. Additionally, it is the only HIV treatment requiring 2 administrations per year.

The novel long-acting treatment was evaluated in a phase 1b trial, which studied safety and efficacy with GS-5423 and GS-2872 in adults with viral suppression and HIV-1 RNA <50 copies/mL and who have had at least 2 years of an antiretroviral therapy (ART).

Patients were randomized 1:1 in 2 active treatment groups, both of which swapped their current ART for 927 mg of subcutaneous lenacapavir (after oral loading) and 30 mg/kg body weight of intravenous GS-5423. The main difference between treatment arms was dose of GS-2872. One arm received 10 mg/kg body weight and the other 30mg/kg body weight.

By week 26, 18 of 20 study participants showed sustained virologic suppression. Only 1 participant withdrew because of viral suppression and 1 participant experienced virologic rebound. The most common adverse events (AEs) at any grade were injection site reactions and nausea, and no grade 4 or 5 AEs were reported or led to drug discontinuation.

“We’re excited to share these promising results that reinforce lenacapavir’s potential to be a foundational agent for long-acting combination HIV treatment options,” said Jared Baeten, MD, PhD, vice president, HIV Clinical Development, Gilead Sciences, in the press release.

Lenacapivir is being evaluated in multiple early and late-stage clinical studies in the company’s research program, although it is not a cure for HIV.

“As a clinician who strives to support the people living with the virus under my care, it will be exciting to continue evaluating the combination regimen as a potential twice-yearly long-acting HIV treatment option,” Eron said in the press release.

Reference

Gilead Sciences, Inc. Gilead Presents Positive Proof-Of-Concept Data For Investigational Combination Regimen Of Lenacapavir With Broadly Neutralizing Antibodies As A Potential Twice-Yearly Approach For The Treatment Of HIV. News Release. February 22, 2023. Accessed February 23, 2023. https://investors.gilead.com/news/news-details/2023/Gilead-Presents-Positive-Proof-of-Concept-Data-for-Investigational-Combination-Regimen-of-Lenacapavir-with-Broadly-Neutralizing-Antibodies-as-a-Potential-Twice-Yearly-Approach-for-the-Treatment-of-HIV/default.aspx