Long-acting HIV-1 Capsid Inhibitor Sustained Efficacy in Phase 2/3 Study

California-based Gilead Sciences, Inc. recently announced new one-year results from the ongoing Phase 2/3 CAPELLA trial evaluating lnacapavir, an investigational, long-acting HIV-1 capsid inhibitor, in heavily treatment-experienced people living with multi-drug resistant HIV.

The findings demonstrated that Lenacapavir, administered subcutaneously every six months in combination with other antiretrovirals, achieved high rates of virologic suppression and clinically meaningful increases in CD4 counts in people living with HIV whose virus was no longer effectively responding to their current therapy.

In this patient population with a high unmet medical need, 83% (n=30/36) of participants receiving Lenacapavir in combination with an optimized background regimen achieved an undetectable viral load (<50 copies/mL) at Week #52.

"I am encouraged by the results presented today showing that the positive outcomes achieved with Lenacapavir can be sustained at one year of treatment, which is a remarkable achievement for this group of people living with HIV who have limited treatment options and are at a greater risk of progressing to AIDS," said Onyema Ogbuagu, MD, FACP, Director of HIV Clinical Trials at Yale School of Medicine, in a Gilead press release issued on Feb. 16, 2022.

"The potential of a long-acting antiretroviral treatment option that may achieve and maintain an undetectable viral load and that is administered only twice a year would be a true advancement that could potentially transform how providers care for certain patients with the virus."

Lenacapavir is Gilead's potential first-in-class, investigational long-acting HIV-1 capsid inhibitor in development to treat and prevent HIV-1 infection.

Lenacapavir's multi-stage mechanism of action is distinguishable from currently approved classes of antiviral agents. As a result, it could provide a new avenue for developing long-acting therapy options for people living with or at risk for HIV-1.

While most antiretroviral agents act on just one stage of viral replication, Lenacapavir inhibits HIV-1 at multiple stages of its lifecycle and has no known cross-resistance to other existing drug classes.

In addition to high rates of viral suppression, participants in CAPELLA achieved a mean increase in CD4 count of 83 cells/µL.

Data previously presented at virtual CROI 2021 showed that the CAPELLA trial achieved its primary endpoint by demonstrating that a significantly higher proportion of participants randomly allocated to receive Lenacapavir (n=24) achieved a clinically meaningful viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those randomly allocated to receive placebo (n=12) during the 14-day functional monotherapy period (88% vs. 17%, p<0.0001).

Those who received Lenacapavir achieved a statistically significant greater mean decrease in viral load than those who received placebo during the functional monotherapy period (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL, p<0.0001).

Lenacapavir is an investigational compound and is not approved by any regulatory authority for any use, and its safety and efficacy are not established.

If approved by the U.S. FDA, Lenacapavir would be the only HIV-1 treatment option administered twice yearly.