Gilead Reports Positive One-Year Results for Twice-Yearly Lenacapavir in Heavily Treatment-Experienced HIV Patients

On February 16, Gilead Sciences announced the new one-year results from the ongoing Phase II/III CAPELLA trial, which evaluated the efficacy of the company’s investigational long-acting HIV-1 capsid inhibitor lenacapavir in heavily treatment-experienced, multidrug-resistant HIV-1 infected individuals.

The study results indicate that for HIV-infected individuals whose virus no longer responds effectively to treatment, receiving a subcutaneous injection of lenacapavir every six months in combination with other antiretroviral drugs can maintain a high rate of viral suppression. Additionally, it leads to a clinically meaningful increase in CD4 count among HIV-infected patients. By week 52, 83% (n=30/36) of participants who received lenacapavir along with an optimized background regimen achieved undetectable viral loads (<50 copies/mL).

Lenacapavir is a potential first-in-class, investigational long-acting HIV-1 capsid inhibitor developed by Gilead Sciences for the treatment and prevention of HIV-1 infection. This is a multimeric shell that is crucial for viral replication at different stages of the virus's life cycle. Most current antiretroviral drugs only target one stage of viral replication, but lenacapavir works by disrupting multiple critical steps in the viral life cycle to inhibit HIV replication. These include inhibiting the uptake, assembly, and release of HIV-1 proviral DNA mediated by the viral capsid, as well as the formation of the viral capsid core, with no known cross-resistance to other existing drug classes. Gilead submitted a marketing application to the FDA in June of last year. If approved, lenacapavir will be the only HIV-1 treatment regimen administered twice a year.

In addition, Gilead has reached a collaboration with Merck to develop a combination therapy of lenacapavir and Merck's islatravir into an oral formulation taken once weekly and an injectable formulation administered once every three months. A Phase II clinical trial has been initiated.

HIV treatment has gradually shifted towards long-acting therapies. In this field, Gilead primarily faces competition from GSK. GSK’s Cabenuva (a co-packaged product of cabotegravir extended-release injectable suspension and rilpivirine extended-release injectable suspension) was approved in February 2021 as the first complete long-acting regimen for adult HIV patients authorized by the FDA, requiring only once-monthly dosing. In February this year, a two-month dosing regimen for Cabenuva also received FDA approval. Additionally, Apretude (cabotegravir extended-release injectable suspension) was approved for marketing in December last year, marking the first long-acting pre-exposure prophylaxis (PrEP) injection therapy for HIV approved by the FDA. GSK stated that it expects its long-acting HIV solutions to generate approximately £2 billion in sales by 2026 (accounting for about one-third of total HIV sales).