New Clinical Data Support the Sustained Efficacy of Long-acting Lenacapavir, Gilead’s Investigational HIV-1 Capsid Inhibitor

Gilead Sciences, Inc. announced new one-year results from the ongoing Phase 2/3 CAPELLA trial evaluating lenacapavir, the company’s 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 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. The data were presented at the 29th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2022).

“I am really 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 program at Yale School of Medicine. “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 for the treatment and prevention of HIV-1 infection. Lenacapavir’s multi-stage mechanism of action is distinguishable from currently approved classes of antiviral agents and could provide a new avenue for the development of 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. If approved, lenacapavir would be the only HIV-1 treatment option administered twice yearly.

“Continued scientific innovation is essential to helping end the global HIV epidemic. Gilead is committed to driving advances in HIV treatment with the goal of offering long-acting options that address the differentiated needs and preferences of a diverse range of individuals and communities impacted by this disease,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “These latest results provide further evidence of the potential for lenacapavir, as a breakthrough innovation, to fulfill the needs of heavily treatment-experienced people living with multi-drug resistant HIV, irrespective of their prior treatment history.”

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 was generally well tolerated in CAPELLA, with one adverse event (AE) leading to study drug discontinuation at Week 52 and no serious adverse events related to lenacapavir. The most common adverse events observed to date in the CAPELLA study were injection site reactions (63%), which were mostly mild or moderate in severity. The most common adverse events, excluding injection site reactions, were nausea and diarrhea (13% each) and COVID-19 (11%).

Gilead presented additional lenacapavir clinical data from the Phase 2 CALIBRATE trial, an ongoing, open-label, active-controlled trial in treatment-naïve people with HIV-1 infection. The trial showed lenacapavir, given subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide (F/TAF) in the first 6 months, followed by combination with either oral daily tenofovir alafenamide (TAF) or bictegravir (BIC), or given orally in combination with emtricitabine/tenofovir alafenamide (F/TAF), achieved high rates of viral suppression by Week 54. Specifically, in the subcutaneous lenacapavir + TAF arm, 90% achieved an undetectable viral load (<50 copies/mL). In the subcutaneous lenacapavir + BIC arm, 85% achieved an undetectable viral load. In the oral lenacapavir + F/TAF arm, 85% achieved an undetectable viral load. Lenacapavir was generally well tolerated, with no study drug-related serious AEs. The most common AEs observed were injection site reactions (ISRs), which were generally mild or moderate in severity. The most frequent non-ISR AEs were headache and nausea (13% each) and COVID-19 (10%).

These results support the ongoing evaluation and further development of lenacapavir in combination with other long-acting partner agents for the treatment of HIV-1 infection and support Gilead’s long-acting oral and injectable development program.

Lenacapavir is an investigational compound and is not approved by any regulatory authority for any use and its safety and efficacy are not established. There is no cure for HIV or AIDS.

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