Gilead Announces Early Data Showing Six-Month Therapeutic Concentration of Investigational HIV-1 Capsid Inhibitor Lenacapavir

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Recently, Gilead Sciences announced data from an ongoing Phase I clinical study at the 23rd International AIDS Conference (AIDS 2020). The study showed that the predicted therapeutic concentration of its investigational novel HIV-1 capsid inhibitor lenacapavir (GS-6207) in a subcutaneous sustained-release formulation would last for at least six months after a single 900 mg dose. In this study, lenacapavir was well tolerated, with no serious adverse events reported.

Lenacapavir is an investigational drug being developed in combination with other antiretroviral agents as a long-acting regimen. Lenacapavir disrupts the HIV capsid, a multimeric protein shell essential for viral replication, at multiple stages of the viral life cycle. In May 2019, the U.S. FDA granted Breakthrough Therapy Designation for the development of lenacapavir in combination with other antiretroviral drugs for the treatment of heavily treatment-experienced individuals with multidrug-resistant HIV-1 infection.

Over the past 30 years, significant progress has been made in the treatment of HIV/AIDS, transforming it into a manageable chronic condition. There is an urgent need for interventions to improve adherence to long-term therapy. Long-acting antiretroviral therapy may help address challenges related to treatment adherence and fatigue, offering a vital therapeutic option for people living with HIV and making HIV a more manageable part of their lives.

Currently, Gilead is conducting multiple clinical studies to evaluate the safety, efficacy, and dosing regimen of lenacapavir.

Lenacapavir Chemical Structural Formula

In this ongoing randomized, blinded, placebo-controlled, single-ascending-dose (SAD) Phase I study, 30 subjects were randomized (4:1) to receive subcutaneous injections of lenacapavir (8 subjects per group) or placebo (2 subjects per group) at doses of 300 mg (1 × 1.0 mL) or 900 mg (3 × 1.0 mL or 2 × 1.5 mL). All subjects completed dosing, and pharmacokinetic and safety data were collected for approximately 64 weeks post-dosing.

Studies have observed that lenacapavir exhibits an initial slow release, with therapeutic plasma concentrations maintained for at least 6 months following a single 900 mg dose (3 × 1.0 mL) injection. Similar results were observed after administering a single 900 mg dose via two 1.5 mL injections. Lenacapavir exposure generally increases in a dose-proportional manner (from 300 mg to 900 mg), reaching maximum concentration 11–14 weeks post-dose, with an apparent half-life of approximately 15 weeks.

Lenacapavir was generally well tolerated, with no serious or Grade 3 or 4 adverse events related to the study drug or leading to discontinuation of the study. The most common adverse reactions were injection site induration (87%), pain (63%), and erythema (70%), all of which were mild. There were no clinically relevant laboratory abnormalities of Grade 3 or higher.

Reference Source: Gilead Sciences Presents Data Supporting a Potential Six-Month Dosing Interval for Investigational HIV-1 Capsid Inhibitor Lenacapavir (GS-6207)