Gilead’s Yeztugo Becomes First FDA-Approved Twice-Yearly HIV Prevention Shot

Gilead Sciences has announced the highly awaited FDA approval of its HIV treatment Yeztugo (lenacapavir).

The therapy is the first and only long-acting injectable for HIV pre-exposure prophylaxis (PrEP) that provides protection for six months with a single dose, meaning it only has to be taken twice a year.

The approval marks a significant step forward in HIV prevention, offering a convenient alternative to daily oral PrEP regimens and monthly or bi-monthly injectable options.

The approval came just ahead of the 13th anniversary of Truvada (emtricitabine/tenofovir disoproxil fumarate), Gilead’s once-daily pill that became the world’s first approved PrEP therapy in 2012.

Yeztugo is authorized for use in adults and adolescents weighing at least 35 kg who are at risk of sexually acquiring HIV-1.

Yeztugo is a first-in-class capsid inhibitor that disrupts HIV at an early stage in its lifecycle. Administered subcutaneously every six months, lenacapavir forms a slow-release depot that maintains protective drug levels in the body, effectively blocking infection.

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“This is a historic day in the decades-long fight against HIV. Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic,” said Daniel O’Day, chairman and CEO of Gilead Sciences.

“This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention. Gilead scientists have made it their life’s work to end HIV and now, with the FDA approval of Yeztugo and in collaboration with our many partners, we can help to make that goal a reality.”

According to Gilead, despite the availability of PrEP, data from the CDC shows that in 2022 — the most recent year with complete data — only 36% of people in the US who met the CDC’s eligibility criteria were prescribed it.

Usage remains uneven across the country, with significant disparities among women, Black/African American and Hispanic/Latino populations, and individuals living in the US South. Barriers such as stigma, low awareness among both healthcare providers and patients, as well as adherence challenges, continue to limit uptake.

These gaps are particularly concerning given that, in 2023, more than 100 people were diagnosed with HIV each day in the US.

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Yeztugo’s approval is backed by data from the Phase III Purpose 1 and Purpose 2 trials, which demonstrated near-complete protection against HIV.

Gilead said the trials represent the “most comprehensive and diverse HIV prevention trial program ever conducted.”

Among cisgender women in sub-Saharan Africa (across South Africa and Uganda) enrolled in Purpose 1, no new HIV infections were observed, amounting to 100% efficacy.

Purpose 2, which enrolled a broader population including gay, bisexual men, transgender people and nonbinary individuals, reported only two infections out of 2,179 participants, resulting in an efficacy rate of greater than 99%.

The treatment also demonstrated superiority over Truvada, with data showing 89% greater effectiveness in reducing HIV risk compared to once-daily Truvada.

In addition to its impressive efficacy, Yeztugo offers a major public health advantage by addressing the persistent challenge of adherence in HIV prevention. Daily oral PrEP like Truvada and the newer Descovy (emtricitabine/tenofovir alafenamide), remains highly effective but can be difficult to maintain over time, especially among marginalized populations who face stigma, logistical barriers or socioeconomic disadvantages.

With just two injections a year, Yeztugo has the potential to greatly improve adherence and reduce disparities in HIV prevention access.

Gilead’s chief commercial officer, Johanna Mercier, described the effort as part of Gilead’s broader strategy to “redefine the PrEP market,” as she noted during an earnings call last summer.

While the company already dominates the market with its current oral therapies, additional options are essential to advance the goal of “ending infections in this country and around the world,” added Jared Baeten, Gilead’s vice president of HIV Clinical Development.

However, Yeztugo’s high list price in the US — approximately $28,000 per year — has drawn criticism from advocacy groups and global health organizations.

While Gilead has committed to providing financial assistance programs for uninsured individuals in the US and expects broad insurance coverage, international health equity advocates warn that the cost could limit accessibility in low- and middle-income countries.

Winnie Byanyima, executive director of UNAIDS, called the US price “too high” and emphasized the importance of making the innovation available to those who need it most.

“UNAIDS has seen research that lenacapavir can be produced for just $40 per person per year, falling to $25 within a year of rollout. It is beyond comprehension how Gilead can justify a price of $28,218. If this game-changing medicine remains unaffordable, it will change nothing,” said Byanyima.

“I urge Gilead to do the right thing. Drop the price, expand production and ensure the world has a shot at ending AIDS.”

To address global access concerns, Gilead has announced a series of licensing and pricing initiatives. The company has entered into voluntary licensing agreements with six generic manufacturers to produce lenacapavir royalty-free for distribution in 120 low-income and middle-income countries, mostly in Africa, Southeast Asia and the Caribbean.

Baeten said Gilead will make enough shots for 2 million people in those countries, at no profit, until generics are available.

Yeztugo adds another milestone to Gilead’s industry-leading HIV portfolio. Its active ingredient, lenacapavir, was first approved under the brand name Sunlenca for adults with multidrug-resistant HIV — a small but critically important population that the company is “so proud” to serve, noted Baeten.

While Gilead has expanded into areas like oncology and liver disease, HIV remains the backbone of its business, with therapies like Biktarvy continuing to drive the majority of the company’s total revenue.

Gilead is also seeking regulatory clearance for Yeztugo in other regions, including the European Union (EU), Canada, Brazil and South Africa.