Gilead Announces Positive Results for HIV-1 Treatment Lenacapavir

Data from the CALIBRATE and CAPELLA trials show high rates of virologic suppression with the capsid inhibitor.

Gilead Sciences has announced new 1-year results from the ongoing phase 2/3 CAPELLA trial that evaluated lenacapavir, an investigational, long-acting HIV-1 capsid inhibitor, in heavily treatment-experienced individuals with multi-drug resistant HIV.

The results showed that the drug, which is administered subcutaneously every 6 months in combination with other antiretrovirals, achieved clinically meaningful increases in CD4 counts and high rates of virologic suppression for this population.

Additionally, for this patient population with high unmet medical needs, 83% of individuals who received the drug in combination with an optimized background regimen achieved an undetectable viral load at week 52.

The data were presented at the 29th Conference on Retroviruses and Opportunistic Infections.

“I am really encouraged by the results presented today showing that the positive outcomes achieved with lenacapavir can be sustained at 1 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,” Onyema Ogbuagu, MD, FACP, director of the HIV clinical trials program at Yale School of Medicine, said in a statement. “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 intended for the prevention and treatment of HIV-1 infection and is distinguishable from approved classes of antiviral agents. This could provide a new avenue for the development of long-acting therapy options for individuals with or at risk for HIV-1.

Although most antiretroviral agents act on just 1 stage of viral replication, lenacapavir targets multiple stages of the HIV-1 lifecycle and has no known cross resistance to other existing drug classes.

Furthermore, if approved, lenacapavir would be the only HIV-1 treatment option administered twice a year.

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

Previous data presented showed that the trial met its primary endpoint by demonstrating that a significantly higher proportion of individuals randomly allocated to receive lenacapavir achieved a clinically meaningful vial load reduction of at least 0.5 log10 copies/mL during the 14-day functional monotherapy period.

The individuals who received lenacapavir achieved a statistically significant greater mean decrease in viral load than those who received the placebo during the functional monotherapy period.

Investigators found that lenacapavir was well tolerated with 1 adverse event (AE) leading to the discontinuation at week 52, and no serious AEs were related to lenacapavir.

The most common AE observed to date was injection site reactions, which were mostly mild or moderate.

Gilead presented additional lenacapavir clinical data from the phase 2 CALIBRATE trial, an active-controlled, ongoing, open-label trial in treatment-naïve individuals 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 bictegravir (BIC) or oral daily tenofovir alafenamide (TAF), or given orally in combination with emtricitabine/tenofovir alafenamide (F/TAF), achieved high rates of viral suppression by week 54. Lenacapavir was generally well-tolerated, with no study drug-related serious AEs. The most common AEs observed were injection site reactions, which were generally mild or moderate in severity.

According to the statement, these results support the ongoing evaluation and further development of lenacapavir in combination with other long-acting partner agents.

Reference

New clinical data support the sustained efficacy of long-acting lenacapavir, Gilead’s investigational HIV-1 capsid inhibitor. Gilead. News release. February 16, 2022. Accessed February 17, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/2/new-clinical-data-support-the-sustained-efficacy-of-longacting-lenacapavir-gileads-investigational-hiv1-capsid-inhibitor