Gilead Advances HIV Treatment Pipeline with New Lenacapavir Combination

Gilead Sciences has made significant strides in its HIV treatment pipeline, announcing key developments during its recent third-quarter earnings call. The pharmaceutical giant is focusing on creating low-frequency treatment options, with lenacapavir at the forefront of these efforts.

GS-3242 Selected as Lenacapavir Partner for Twice-Yearly Treatment

In a strategic move, Gilead has chosen to pair its integrase strand transfer inhibitor GS-3242 with lenacapavir for development as a twice-yearly injectable HIV treatment. This decision comes after comparing two phase 1 candidates, with GS-3242 emerging as the preferred option over GS-1219. Consequently, Gilead has discontinued a phase 1 study of GS-1219 in people with HIV.

Dr. Dietmar Berger, Gilead's Chief Medical Officer, explained the company's approach: "Our strategy has been to set up our pipeline for multiple shots on goal and then choose the best option for each dosing frequency." Gilead plans to share more details about GS-3242 at a virology conference in 2026, signaling confidence in the compound's potential.

Lenacapavir's Growing Impact on HIV Treatment and Prevention

Lenacapavir, Gilead's groundbreaking capsid inhibitor, has already made waves in the HIV treatment landscape. In June, it received approval for HIV prevention under the brand name Yeztugo, a development that Gilead CEO Daniel O'Day hailed as "one of the most important scientific breakthroughs of our time." The significance of this advancement was further underscored when Science named lenacapavir its 2024 Breakthrough of the Year, following its remarkable performance in a large phase 3 trial where it demonstrated 100% efficacy.

The drug's journey began with its 2022 approval as Sunlenca for treatment-resistant HIV, and Gilead is now leveraging its potential across multiple treatment modalities. In addition to the twice-yearly injectable formulation with GS-3242, the company is exploring weekly oral treatments in collaboration with Merck, combining lenacapavir with islatravir in a phase 3 trial. Gilead is also investigating a daily oral treatment option, pairing lenacapavir with its own integrase inhibitor, bictegravir, which is already part of the successful Biktarvy cocktail.

Challenges and Ongoing Research

While Gilead pushes forward with its lenacapavir combinations, the company faces some hurdles in its broader HIV research efforts. Two phase 2/3 trials testing investigational treatments GS-1720 and GS-4182 were placed on hold by the FDA in June due to safety concerns, with the holds remaining in effect as of the latest update.

Despite these setbacks, Gilead continues to explore additional avenues for HIV treatment. The company is testing GS-1614, a prodrug of islatravir, as a potential quarterly injectable HIV treatment in combination with lenacapavir. This diverse approach to treatment frequencies and delivery methods demonstrates Gilead's commitment to providing a range of options for people living with HIV.