Gilead Announces Additional Results from Phase 2/3 CAPELLA Trial of Investigational Lenacapavir in Heavily Treatment-Experienced People with Multidrug-Resistant HIV-1

Gilead Sciences recently announced additional results from the Phase 2/3 CAPELLA trial at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI).

This trial evaluated the efficacy and safety of lenacapavir (GS-6207) in patients with multidrug-resistant HIV-1 infection who had previously received multiple therapies. The top-line results announced in November 2020 showed that at the end of the 14-day functional monotherapy period, 88% (n=21/24) of patients in the lenacapavir group achieved a reduction in HIV-1 viral load of at least 0.5 log10 copies/mL, compared to only 17% (n=2/12) of patients in the placebo group.

The newly announced interim efficacy results demonstrate that in patients with refractory disease who have limited treatment options and unmet medical needs, lenacapavir administered via subcutaneous injection every six months maintained a high rate of virologic suppression over 26 weeks. In this analysis of the CAPELLA ongoing maintenance phase, among subjects evaluated from the first subcutaneous injection of lenacapavir through Week 26 while receiving lenacapavir in combination with an optimized background regimen, 73% (n=19/26) achieved undetectable viral loads (<50 copies/mL).

In addition to the new interim results from the CAPELLA trial, Gilead also presented findings from a preclinical study in non-human primates evaluating GS-CA1, a close analog of lenacapavir, for HIV pre-exposure prophylaxis (PrEP). In this study, animals received a single injection of either low-dose (150 mg/kg) or high-dose (300 mg/kg) GS-CA1, or placebo (n=8 per group), followed by weekly escalating rectal SHIV challenges for 15 weeks, with monitoring continued through Week 24.

Overall, 100% (8/8) of animals in the placebo group became infected, whereas 2/8 and 5/8 of animals in the low-dose and high-dose GS-CA1 groups, respectively, remained protected, resulting in an 86% (p=0.0061) and 96% (p=0.0002) reduction in infection risk, respectively. Notably, infections in the treatment groups occurred only after significant drug washout. These preclinical data demonstrate the potential utility of long-acting capsid inhibitors in preventing HIV infection and may help advance clinical studies evaluating lenacapavir as a potential monotherapy option for future HIV prevention.

Lenacapavir is an investigational, first-in-class, novel, selective HIV-1 capsid inhibitor. Compared with currently available antiretroviral agents, lenacapavir works through a novel mechanism by blocking the activity of the HIV capsid, a protein that surrounds and protects the viral genetic material and essential enzymes. In vitro studies have demonstrated that lenacapavir can block multiple distinct stages of the viral life cycle, with the potential to prevent viral infection and transmission to uninfected cells.

Lenacapavir exhibits potent antiviral activity, rapidly reducing viral load after a single subcutaneous injection. It is currently being developed as part of a long-acting regimen, in combination with other antiretroviral agents, for the treatment and prevention of HIV-1 infection.

If approved, lenacapavir will become the first HIV capsid inhibitor available for the treatment of HIV-1 infection. In May 2019, the U.S. FDA granted Breakthrough Therapy Designation (BTD) to lenacapavir, in combination with other antiretroviral agents, for use in patients with multidrug-resistant HIV-1 who have previously undergone multiple treatment regimens.

Currently, the safety, efficacy, and dosing regimen of lenacapavir are being evaluated in multiple clinical trials. Gilead Sciences previously announced plans to evaluate lenacapavir as a semiannual (every 6 months) injectable formulation for HIV pre-exposure prophylaxis (PrEP), with the company expecting to initiate two PrEP studies in 2021.

Original Source: Gilead’s Investigational Lenacapavir Demonstrates Sustained Long-Acting Efficacy Through Week 26 in Data Presented at CROI

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