Gilead Submits NDA for Lenacapavir: Twice-Yearly Long-Acting HIV Therapy Demonstrates Durable Efficacy in Phase 2/3 Trials

Recently, Gilead Sciences announced the latest results from the Phase 2/3 CAPELLA clinical trial of its investigational long-acting HIV-1 capsid inhibitor, lenacapavir, at the 11th International AIDS Society (IAS) Conference. The trial results demonstrated that subcutaneous administration of lenacapavir once every six months, in combination with other antiretroviral drugs, resulted in 81% (n=29/36) of participants living with multidrug-resistant HIV achieving an undetectable viral load (<50 copies/mL) at Week 26.

Lenacapavir is a potential "first-in-class" capsid inhibitor developed by Gilead Sciences, Inc. It interferes with the assembly and disassembly of the HIV capsid protein, functioning at multiple stages of the HIV-1 life cycle. In May 2019, lenacapavir was granted Breakthrough Therapy designation by the U.S. FDA for use in combination with other antiretroviral therapies to treat heavily treatment-experienced individuals with multidrug-resistant HIV-1 infection.

The key advantage of lenacapavir is that patients may only require an injection once every six months to maintain therapeutic efficacy. However, it currently still requires co-administration with other daily oral antiretroviral agents. Previously, Gilead Sciences entered into a collaboration agreement with Merck & Co. (MSD) to jointly develop a complete long-acting HIV combination therapy regimen comprising lenacapavir and MSD’s innovative nucleoside reverse transcriptase translocation inhibitor (NRTTI), islatravir. In late June of this year, Gilead Sciences submitted a New Drug Application (NDA) for lenacapavir to the FDA.

▲ Overview of Lenacapavir Therapy (Image source: Gilead Sciences official website)

In addition to 81% of subjects in the CAPELLA trial achieving an undetectable viral load at Week 26, subjects experienced a mean increase in CD4+ T-cell count of 81 cells/μL. Previously reported results demonstrated that patients receiving lenacapavir achieved a viral load reduction of 1.93 log10 copies/mL from baseline, significantly greater than that observed in the placebo group (0.29 log10 copies/mL). Additionally, a higher proportion of patients achieved a viral load reduction of >0.5 log10 copies/mL (88% vs 17%, p<0.0001).

Additionally, Gilead announced the results of the Phase 2 CALIBRATE trial evaluating oral or subcutaneous lenacapavir in combination with oral emtricitabine/tenofovir alafenamide (F/TAF) for the treatment of treatment-naive HIV-1-infected patients. The trial results demonstrated that this combination achieved viral suppression in 94% of treatment-naive patients at Week 28.

Note: The original text has been abridged.

References:

[1] New Phase 3 Data Support the Sustained, Long-Acting Efficacy of Lenacapavir, Gilead's Investigational HIV-1 Capsid Inhibitor. Retrieved July 17, 2021, from https://www.businesswire.com/news/home/20210717005010/en

▽Follow【WuXi AppTecVirtue】WeChat Official Account