Breakthrough in HIV Prevention: FDA Approves Yeztugo, a Twice-Yearly Injectable Drug -FDA

In a landmark advancement for HIV prevention, the U.S. Food and Drug Administration (FDA) has approved Yeztugo (lenacapavir), a twice-yearly injectable medication developed by Gilead Sciences, Inc. This approval marks the first and only HIV pre-exposure prophylaxis (PrEP) option that requires just two injections per year, offering a revolutionary alternative to daily oral medications. Yeztugo, a novel HIV-1 capsid inhibitor, has demonstrated near-perfect efficacy in clinical trials, sparking hope for a significant reduction in new HIV infections worldwide. However, concerns about affordability and accessibility remain, as advocates call for equitable distribution to ensure the drug reaches those who need it most.

Yeztugo is administered as two subcutaneous injections in the abdomen, six months apart, creating a “depot” of medication that is slowly absorbed by the body. This long-acting approach addresses a critical challenge in HIV prevention: adherence to daily pill regimens, which can be difficult for some individuals due to logistical, social, or stigma-related barriers. Unlike other PrEP options, such as Gilead’s daily oral drugs Truvada and Descovy, Yeztugo’s bi-annual dosing aligns with routine medical visits, potentially increasing compliance and effectiveness.

Clinical trials have showcased Yeztugo’s remarkable efficacy. In the Phase 3 PURPOSE 1 trial, conducted among over 5,300 cisgender women and adolescent girls aged 16 to 26 in South Africa and Uganda, Yeztugo achieved a 100% efficacy rate, with zero HIV infections reported among the 2,134 participants receiving the drug. In comparison, 16 infections occurred in the Truvada group, and 39 in the Descovy group. The PURPOSE 2 trial, which included cisgender men, transgender people, and gender-diverse individuals across global sites, reported a 99.9% efficacy rate, with only two infections among 2,179 participants, translating to an 89% risk reduction compared to Truvada and a 96% reduction compared to no PrEP at all. These results led the journal Science to name lenacapavir its 2024 “Breakthrough of the Year.”

Gilead’s CEO, Daniel O’Day, hailed the approval as a “historic day in the decades-long fight against HIV,” stating that Yeztugo “offers a very real opportunity to help end the HIV epidemic.” The drug’s unique mechanism as a capsid inhibitor, which disrupts multiple stages of the HIV lifecycle, sets it apart from other antiretrovirals and minimizes cross-resistance risks, even in drug-resistant strains.

Safety and Administration

Yeztugo is approved for adults and adolescents weighing at least 35 kg (77 lbs) who are at risk of sexually acquired HIV. A critical safety requirement is that individuals must test negative for HIV-1 before starting and continuing Yeztugo, as use in those with undiagnosed HIV could lead to drug-resistant variants. The FDA has issued a Boxed Warning emphasizing this risk. Common side effects include injection-site reactions, headaches, and nausea, but the drug has demonstrated a favorable safety profile in trials.

The drug is administered by healthcare providers in clinical settings, ensuring proper testing and monitoring. Its long-acting nature, with the drug remaining in the body for up to 12 months, underscores the importance of consistent HIV testing to avoid missed doses or improper use, which could increase infection risk or resistance.

Market Impact and Analyst Outlook

Yeztugo’s approval is poised to redefine the PrEP market, which is projected to grow to $40 billion with a 4.6% annual growth rate. Analysts predict strong commercial uptake due to the drug’s efficacy, convenient dosing, and clean safety profile. Citi Research analyst Geoff Meacham forecasts annual sales of $2.8 billion by 2030, with 75% of U.S. insurers, including government health plans, expected to cover Yeztugo within six months of launch, rising to 90% within a year. Mizuho analysts note that Yeztugo could “redefine” the PrEP market, positioning Gilead to capture significant market share alongside GSK and ViiV’s Aprectude, the only other long-acting PrEP option.

Gilead’s stock (Nasdaq: GILD) has gained momentum following the approval, with analysts maintaining an Outperform rating and a target price of $120, reflecting optimism about the company’s growth in the PrEP sector.

Accessibility and Affordability Challenges

Despite its transformative potential, Yeztugo’s high cost has raised concerns. Priced at approximately $28,218 annually in the U.S., or about $14,000 per injection, the drug’s cost is in line with other branded PrEP medications but significantly higher than generic Truvada. An analysis by the University of Liverpool suggests that Yeztugo could be produced for as little as $25 per year, including a 30% profit margin, highlighting the stark contrast between production costs and market pricing.

Public health advocates, including Kevin Robert Frost, CEO of the Foundation for AIDS Research, have emphasized that Yeztugo “will only be as effective as it is accessible and affordable.” Gilead has announced patient assistance programs, including free access for uninsured low-income individuals, and plans to pursue voluntary licensing agreements to improve access in low-income countries. Some telehealth companies and community clinics in urban areas with high HIV incidence are preparing to provide Yeztugo, but advocates stress the need for broader coverage to ensure equitable access.

The Trump administration’s cuts to HIV prevention and treatment infrastructure, both domestically and globally, have further complicated the rollout. While some domestic cuts have been rolled back, uncertainties remain about how Yeztugo will reach underserved populations.

A Step Toward Ending the HIV Epidemic

With over 30,000 new HIV infections annually in the U.S. and 1.3 million worldwide, Yeztugo’s approval comes at a critical time, as global efforts to end the HIV pandemic by 2030 have stalled. The drug’s near-100% efficacy offers a powerful tool to interrupt HIV transmission, particularly for high-risk populations. However, its success hinges on overcoming economic and political barriers to ensure widespread availability.

Gilead is pursuing regulatory filings worldwide and collaborating with global partners to expand access. The company’s prior approval of lenacapavir (under the brand name Sunlenca) for multi-drug-resistant HIV treatment in multiple countries demonstrates its commitment to addressing the global HIV epidemic.

As the world celebrates this scientific breakthrough, the focus now shifts to ensuring that Yeztugo reaches those who need it most. With continued advocacy and strategic partnerships, this twice-yearly injection could pave the way for a future where HIV transmission is significantly reduced, bringing us closer to ending the epidemic that has persisted for over four decades.