Lenacapavir NDA Submitted for HIV-1 in Heavily Treatment Experienced Patients

A New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for lenacapavir for the treatment of HIV-1 infection in heavily treatment experienced patients with multidrug resistant (MDR) HIV-1 infection.

Lenacapavir is an investigational, long-acting HIV-1 capsid inhibitor. It is designed to inhibit HIV replication by interfering with capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation.

The NDA submission is supported by data from the global, multicenter, double-blind, placebo-controlled phase 2/3 CAPELLA trial (ClinicalTrials.gov Identifier: NCT04150068), which assessed the efficacy and safety of lenacapavir in 36 heavily treatment experienced patients with MDR HIV-1 infection. Patients were randomly assigned 2:1 to receive oral lenacapavir or placebo for 14 days, in addition to continuing their failing regimen (functional monotherapy period).

Findings showed that a significantly greater proportion of patients treated with lenacapavir met the primary endpoint achieving a viral load reduction of at least 0.5 log₁₀ copies/mL from baseline in HIV-1 RNA compared with those treated with placebo (88% vs 17%; P <.0001). A statistically significantly greater mean decrease in viral load was observed in lenacapavir-treated patients compared with those who received placebo (-1.93 log₁₀ copies/mL vs -0.29 log₁₀ copies/mL; P <.0001).

After the 14 day functional monotherapy period, participants were enrolled in the maintenance phase of the trial, which assessed the efficacy and safety of lenacapavir administered subcutaneously every 6 months in combination with an optimized background regimen. Interim results showed that 73% (n=19/26) of patients who reached week 26 after receiving 1 dose of lenacapavir subcutaneously achieved undetectable viral load of less than 50 copies/mL.

Regarding safety, lenacapavir was generally well tolerated with the most common adverse events being injection site reactions. There were no serious adverse events related to lenacapavir.

“Lenacapavir is an important breakthrough innovation with the potential to be transformative for people living with multidrug resistant HIV who have very limited treatment options,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “The filing moves us one step closer to providing an innovative treatment option that helps to address barriers to achieving viral suppression and meet the unmet needs of people living with multidrug resistant HIV.”

References

1. Gilead submits New Drug Application to US Food and Drug Administration for lenacapavir, an investigational, long-acting capsid inhibitor for the treatment of HIV-1 in people with limited therapy options. [press release]. Foster City, CA: Gilead Sciences, Inc.; June 28, 2021. 
2. Gilead’s investigational lenacapavir demonstrates sustained long-acting efficacy through week 26 in data presented at CROI. [press release]. Foster City, CA: Gilead Sciences, Inc.; March 9, 2021.