European Commission Approves Twice-Yearly Lenacapavir (Yeytuo®) for HIV Prevention

08/26/2025 – 03:00 AM

– Yeytuo^® Gets Green Light in Europe: The First and Only EC-Approved HIV PrEP Offering Six Months of Protection

– Fast-Track Approval Follows FDA’s Nod in June, Signalling Urgency

FOSTER CITY, Calif. – Gilead Sciences (GILD) is making waves in HIV prevention. The European Commission (EC) has granted marketing authorization for Yeytuo^® (lenacapavir), Gilead’s innovative twice-yearly injectable HIV-1 capsid inhibitor. This approval allows Yeytuo to be used as pre-exposure prophylaxis (PrEP), significantly reducing the risk of sexually acquired HIV-1 in high-risk adults and adolescents (weighing at least 35kg). This positions Yeytuo as the first and only twice-yearly PrEP option in the 27 EU member states, plus Norway, Iceland, and Liechtenstein.

The EC’s decision came swiftly, reviewing the marketing authorization application (MAA) under an accelerated timeline. The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) deemed Yeytuo a product of major public health interest. Back in July, the CHMP issued a positive opinion recommending EC authorization. The new indication also grants lenacapavir an additional year of market protection in the EU, acknowledging its significant clinical benefit over existing therapies. This extended protection, however, requires scientific evaluation prior to authorization.

“The rapid authorization by the European Commission highlights the robust clinical data and Yeytuo’s potential to address the unmet needs in European HIV prevention,” stated Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences. “This achievement reflects 17 years of Gilead’s dedicated research and decades of leadership in HIV innovation.”

This EC authorization follows the U.S. Food and Drug Administration (FDA)’s approval in June, and the World Health Organization (WHO)’s July guidelines that recommended twice-yearly lenacapavir as a PrEP option.

Jean-Michel Molina, MD, Université Paris Cité, Professor of Infectious Diseases and Head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, emphasizes the importance of new prevention methods. “With approximately 25,000 new HIV diagnoses annually in the EU and European Economic Area, current prevention options are insufficient, particularly among vulnerable populations,” Molina said. “Yeytuo’s unique dosing schedule and high efficacy could revolutionize HIV prevention, significantly reducing new infections and driving progress toward ending the HIV epidemic in Europe.”

The EC Authorization is Backed by Strong Data

The Phase 3 PURPOSE 1 and PURPOSE 2 trials supplied the data supporting the EC authorization. In the PURPOSE 1 trial (NCT04994509), the primary analysis showed zero HIV infections among 2,134 participants receiving twice-yearly subcutaneous lenacapavir, demonstrating a 100% reduction in HIV infections compared to once-daily oral Truvada^® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) in cisgender women in sub-Saharan Africa. Meanwhile, in the PURPOSE 2 trial (NCT04925752), only two HIV infections occurred among 2,179 participants in the lenacapavir group, reflecting 99.9% efficacy when compared with once-daily oral Truvada among a diverse group of cisgender men and gender-diverse individuals. Lenacapavir demonstrated superiority over background HIV incidence (bHIV) in both trials, and was generally well-tolerated, without any major safety concerns. Data from the trials were published in The New England Journal of Medicine, and lenacapavir was named Science’s 2024 “Breakthrough of the Year.”

Global Regulatory Strategy and Partnerships

Gilead’s global access strategy focuses on expediting regulatory review, approval, and access to twice-yearly lenacapavir for PrEP. Besides the U.S. and EU approvals, Gilead has submitted applications in Australia, Brazil, Canada, South Africa, and Switzerland. Preparations are also underway for filings in Argentina, Mexico, and Peru.

Following the EU-Medicines for all (EU-M4all) positive opinion, Gilead plans to submit applications to national regulatory authorities in low- and middle-income countries (LMIC), streamlining reviews. This covers 18 countries representing 70% of the HIV burden across the 120 countries included in Gilead’s prior voluntary licensing agreements. The EU-M4all procedure also streamlines WHO prequalification. Additionally, Gilead has a strategic partnership with The Global Fund to Fight AIDS, Tuberculosis and Malaria, aimed at supplying lenacapavir for PrEP to up to two million people in primarily low- and lower-middle-income countries, pending approval.

Lenacapavir for PrEP remains unapproved by regulatory bodies outside the U.S. and EU. Currently, there is no known cure for HIV or AIDS.

About Lenacapavir

Lenacapavir is approved as PrEP to reduce the risk of sexually acquired HIV in adults and adolescents at risk. It is also approved in multiple countries for treating multi-drug-resistant HIV in adults, when combined with other antiretrovirals.

Lenacapavir inhibits HIV at multiple stages of its lifecycle, acting differently from existing antiviral drugs. It has no known cross-resistance to other drug classes in vitro. As a long-acting option, it is evaluated in numerous early and late-stage clinical studies, with the goal of providing oral and injectable options for different dosing preferences.

EU Indication for Yeytuo^®

Yeytuo^® injection, in combination with safer sex practices, is indicated for PrEP to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents with increased HIV-1 acquisition risk weighing at least 35kg.

U.S. Indication for Yeztugo^®

Yeztugo^® (lenacapavir) injection, 463.5 mg/1.5 mL, is indicated for PrEP to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35kg) at risk for HIV-1 acquisition. Individuals must test negative for HIV-1 before starting Yeztugo.

U.S. Important Safety Information for Yeztugo

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO IN UNDIAGNOSED HIV-1 INFECTION

• Individuals must undergo HIV-1 testing before initiating Yeztugo, and with each subsequent injection of Yeztugo, using an FDA-approved test to diagnose acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been detected with Yeztugo use in individuals with undiagnosed HIV-1 infection. Yeztugo should only be initiated once negative infection status is confirmed. Individuals acquiring HIV-1 while receiving Yeztugo must transition to a comprehensive HIV-1 treatment regimen.

Contraindications

• Yeztugo is contraindicated in individuals with unknown or positive HIV-1 status.

Warnings and precautions

• Comprehensive risk management:
  • Use Yeztugo to reduce HIV-1 acquisition risk as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce sexually transmitted infections (STIs).

  • HIV-1 acquisition risk includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or present STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network. Counsel individuals on other prevention methods to reduce their risk.

  • Use Yeztugo only in individuals confirmed HIV-1 negative. Evaluate for current or recent signs or symptoms suggesting HIV-1 infection. Confirm HIV-1 negative status before initiating, before each subsequent injection, and as clinically appropriate.

• Potential risk of resistance:
  • There is a potential risk of developing resistance to Yeztugo if an individual acquires HIV-1 before or when receiving Yeztugo, or after discontinuation. HIV- 1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection taking only Yeztugo, because Yeztugo alone is not a full HIV-1 treatment regimen.

  • To minimize this risk, testing before each injection and as clinically appropriate is essential. Individuals confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen.

  • Alternative forms of PrEP should be considered after Yeztugo discontinuation for those at continuing HIV-1 acquisition risk and initiated within 28 weeks of the last Yeztugo injection.

• Long-acting properties and potential associated risks:
  • Residual concentrations of Yeztugo may remain in systemic circulation for up to 12 months or longer following the last injection.

  • Select individuals who agree to the required injection dosing schedule because nonadherence or missed doses could lead to HIV-1 acquisition and development of resistance.

• Serious injection site reactions: Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer. Administer Yeztugo subcutaneously only.

Adverse reactions

• Most common adverse reactions (≥5%) in Yeztugo clinical trials were injection site reactions, headache, and nausea.

Drug interactions

• Strong or moderate CYP3A inducers may significantly decrease Yeztugo concentrations. Dosage modifications are recommended when initiating these inducers.

• It is not recommended to use Yeztugo with combined P-gp, UGT1A1, and strong CYP3A inhibitors.

• Coadministration of Yeztugo with sensitive CYP3A or P-gp substrates may increase their concentrations and the risk of adverse events. Yeztugo may increase exposure to drugs primarily metabolized by CYP3A initiated within 9 months after the last Yeztugo injection.

Dosage and administration

• HIV screening: Test for HIV-1 infection prior to initiating, prior to each subsequent injection, and as clinically appropriate using an approved test for the diagnosis of acute or primary HIV-1 infection.

• Dosage: Initiation dosing (injections and tablets) followed by continuation injection dosing once every 6 months. Tablets may be taken with or without food.
  • Initiation: Day 1: 927 mg by subcutaneous injection (2 x 1.5-mL injections) and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally.

  • Continuation: 927 mg by subcutaneous injection every 6 months (26 weeks) from date of last injection ±2 weeks.

• Anticipated delayed injections: If the scheduled 6-month injection will be delayed by more than 2 weeks, Yeztugo tablets may be taken on an interim basis (for up to 6 months) until injections resume. Dosage is 300 mg orally (1 x 300-mg tablet) once every 7 days. Resume continuation injections within 7 days of the last oral dose.

• Missed injections: If more than 28 weeks have elapsed since the last injection and Yeztugo tablets have not been taken, restart with initiation dosing if clinically appropriate.

• Dosage modifications of Yeztugo are recommended when initiating with strong or moderate CYP3A inducers. Consult the full Prescribing Information for recommendations.

About Gilead HIV

Gilead has been at the forefront of HIV innovation for over 35 years, driving progress in treatment, prevention, and cure research. Gilead researchers have developed 13 HIV medications, including the first single-tablet regimen, the first antiretroviral for PrEP, and the first long-acting injectable HIV treatment administered twice-yearly. Their advancements have transformed HIV into a manageable, preventable, chronic condition for millions.

Gilead is committed to continued scientific innovation, offering solutions for the evolving needs of people affected by HIV around the world. Through partnerships, collaborations, and charitable giving, the company aims to improve education, expand access, and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as a leading philanthropic funder of HIV-related programs.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company dedicated to creating a healthier world for all through breakthroughs in medicine. They develop innovative medicines to prevent and treat life-threatening diseases including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in over 35 countries, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements subject to risks, uncertainties, and other factors. These include Gilead’s ability to initiate, progress, and complete clinical trials, the possibility of unfavorable results from ongoing and additional clinical trials including PURPOSE 1 and PURPOSE 2 involving lenacapavir; uncertainties relating to regulatory applications and approval timelines for lenacapavir for PrEP, and the risk that any approvals may be subject to limitations. There’s also the possibility that Gilead may discontinue development of lenacapavir, the risk that physicians may not see the benefits of prescribing Yeztugo/Yeytuo for PrEP, and Gilead’s ability to effectively manage the access strategy relating to lenacapavir. These and other risks are detailed in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed with the U.S. Securities and Exchange Commission. Actual results could differ materially from these forward-looking statements. Gilead assumes no obligation to update these statements.

U.S. full Prescribing Information for Truvada, Yeztugo and Yeytuo, including Boxed Warning, are available at www.gilead.com.

Truvada, Truvada for PrEP, Yeztugo, Yeytuo, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).

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Source: Gilead Sciences, Inc.