Gilead’s Lenacapavir Shows Promise for Multidrug-Resistant HIV in Phase II/III Trial

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Topline results from Gilead Sciences Phase II/III CAPELLA trial show that treatment with the company’s long-acting HIV-1 capsid inhibitor lenacapavir reduces HIV viral load better than placebo in heavily treated patients living with multidrug resistant HIV-1 infection.

There is currently a significant unmet need for effective treatment options that address the complexities involved in heavily treated and multidrug-resistant HIV. Novel investigational capsid inhibitor lenacapavir represents a potential advancement in the field of HIV therapy, said Diana Brainard, M.D., Senior Vice President and Virology Therapeutic Area Head, Gilead Sciences, in a statement.

Lenacapavir, if approved, would be the first HIV capsid inhibitor that can be prescribed to treat heavily treated HIV-1 infection. The FDA granted Breakthrough Therapy Designation to lenacapavir in May 2019 to further support the development of the drug for HIV-1 infection in heavily treatment-experienced patients with multidrug resistance in combination with other antiretroviral agents.

Similarly, ViiV Healthcare recently received Breakthrough Therapy Designation for its long-acting injectable cabotegravir for HIV pre-exposure prophylaxis. The designation was based on Phase IIb/III efficacy and safety data involving Gilead’s Truvada drug.

The CAPELLA trial has enrolled 36 adults with multi-class HIV drug resistance who had a detectable viral load and were receiving a failing regimen. Participants were randomly assigned to oral lenacapavir or placebo for a 14-day period, with no change to their failing treatment regimen.

A significantly greater proportion of patients in the lenacapavir group met the primary endpoint of a viral load reduction of at least 0.5 log10 copies/mL compared with the placebo arm at the end of the study period (88% vs. 17%, respectively; p<0.0001). Treatment with lenacapavir also resulted in a significantly greater mean change in viral load (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL; p<0.0001).

No serious adverse events related to treatment were observed, and none of the patients discontinued the drug for any reason. Most common adverse events were injection site swelling (21%) and injection site nodules (17%), and most of these were Grade 1 or 2 in severity.

The researchers say more details on the study and its findings will be revealed at an upcoming medical conference.

“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,” according to a statement made by Edwin DeJesus, MD, FACP, FIDSA, Medical Director, Orlando Immunology Center. “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 new data from the CAPELLA trial add to preliminary Phase I data presented by the company in July at the 23rd International AIDS Conference. The investigators of this study found that a delivery of subcutaneous lenacapavir resulted in sustained predicted therapeutic concentrations for at least six months after a single 900 mg dose. And in October, researchers presented an oral abstract session at the HIV Glasgow 2020 conference of a lenacapavir resistance analysis from a Phase Ib clinical proof-of-concept study.

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