Lenacapavir Reaches Primary Endpoint in Study in People Living with HIV

Gilead announced this week that its investigational long-acting HIV-1 capsid inhibitor, lenacapavir, has achieved its primary endpoint in a phase 2/3 CAPELLA trial.

A recent Phase 2/3 Capella trial conducted by Gilead Sciences, Inc. on its investigational, long-acting HIV-1 capsid inhibitor, lenacapavir, has reached its primary endpoint, the company announced.

Lenacapavir, a long-acting HIV-1 capsid inhibitor, acts in a more novel way in comparison to the currently available antiretroviral agents. HIV capsid, a protein that protects the virus’ genetic material by surrounding it, is interrupted by lenacapavir. This further disrupts various stages in the virus’ lifecycle, potentially prohibiting it from becoming infectious and spreading to other healthy cells.

The study involved 36 adults who were diagnosed with multi-class HIV drug resistance, as well as a detectable viral load while on a failing regimen. The participants were randomized 2:1 and received oral lenacapavir or a placebo while continuing on their current failing regimen for 14 days. At the end of the two-week period, a statistically significant proportion of the group receiving the treatment had a viral load reduction of at least 0.5 log10 copies/mL from baseline. The lenacapavir group also had a greater mean change in viral load when compared to the placebo group.

The therapy had no serious adverse effects and was demonstrated to be well-tolerated and altogether safe. The most common side effects that occurred were grade 1 or 2 injection site nodules (17%) as well as injection site swelling (21%), and no discontinuations of the medication occurred during the trial period.

“There is an urgent and critical need for innovative treatment options for people living with HIV who have limited treatment options and are not able to maintain virologic suppression on their current therapy, whether from challenges adhering to a complex regimen or HIV mutations that cause drug resistance,” Edwin DeJesus, MD, FACP, FIDSA, said. “The initial CAPELLA trial results demonstrate that lenacapavir led to a rapid decline in viral load in heavily treatment-experienced people with multidrug resistance living with HIV. This clinical response could potentially have an important impact on individual patients and public health.”

The efficacy, dosing and safety of lenacapavir are at this time being investigated further in a multitude of ongoing clinical studies. Current data shows support for lenacapavir being administered subcutaneously every six months for both the treatment and prevention of HIV. An additional PrEP study is planned for mid to late 2021.