FDA Approval and Access Strategy for Lenacapavir (Yeztugo) Long-Acting HIV Prevention

Summary

The FDA has approved Yeztugo (lenacapavir), a revolutionary twice-yearly injection that redefines long-acting HIV prevention. With 96% efficacy in cisgender women and 100% efficacy in men who have sex with men and gender-diverse individuals, it addresses adherence challenges of daily oral PrEP. This breakthrough offers a transformative approach to HIV prevention, reducing pill fatigue and enhancing accessibility for high-risk populations worldwide.

Key Insights

• High efficacy and adherence potential: Lenacapavir’s 6-month dosing eliminates daily pill routines, enhancing adherence among high-risk populations for long-acting HIV prevention.
• Novel mechanism: As the first capsid inhibitor, it disrupts viral assembly by targeting a new area in the HIV lifecycle.
• Dual clinical utility: Yeztugo is approved for treating multi-drug-resistant HIV and as a preventive measure, offering essential flexibility.

Background Context

HIV pre-exposure prophylaxis (PrEP) has relied on daily oral medications like Truvada and Descovy. These require strict adherence, but pill fatigue and access barriers have limited their use. The World Health Organization highlights lenacapavir as a breakthrough, especially for resource-limited settings. Initially approved in 2022 for multi-drug-resistant HIV, it now has preventive applications.

Access Strategies Implications

Gilead’s access strategy for Yeztugo, as outlined in their June 18, 2025, announcement, emphasizes speed, efficiency, and collaboration to ensure broad reach. The company is leveraging multiple channels—insurance coverage, assistance programs, and global regulatory filings—to drive uptake. However, the strategy’s success hinges on navigating complex market dynamics and stakeholder needs. Below are the expanded implications:

Health economics and system efficiency:

Yeztugo’s twice-yearly dosing reduces the frequency of medical visits compared to daily pills or bimonthly injections like Apretude, potentially lowering administrative and patient travel costs. However, the $28,218 annual U.S. list price and the need for trained healthcare providers to administer injections could strain budgets, especially for public health programs. Gilead’s commitment to co-pay assistance for insured patients and free access for eligible uninsured individuals through the Advancing Access program aims to ease this burden. Over time, these initiatives could shift resources toward broader prevention campaigns, but initial costs may challenge smaller clinics or underfunded systems. Payers and providers will need to balance upfront investment against long-term savings from reduced HIV transmission and treatment costs.

Public health outcomes and market expansion:

Lenacapavir’s high efficacy and simplified dosing could drive significant reductions in HIV incidence, particularly among marginalized groups where adherence to daily PrEP is low. The PURPOSE 1 and 2 trials demonstrated near-zero breakthrough infections, suggesting Yeztugo could outperform existing options if widely adopted. Gilead’s strategy to secure insurance coverage within six to twelve months in the U.S. signals a push for rapid market penetration. By addressing adherence barriers, Yeztugo could expand the PrEP market, attracting individuals previously deterred by daily regimens or stigma. This could create a virtuous cycle: higher uptake reduces transmission, which lowers future healthcare costs and reinforces demand for long-acting solutions. However, success depends on overcoming logistical hurdles, such as ensuring consistent follow-up for biannual injections, especially in transient or underserved populations.

Global equity and strategic partnerships:

Gilead’s global ambitions for Yeztugo include regulatory filings in Europe, Australia, Brazil, Canada, South Africa, and countries reliant on FDA approval, such as Argentina, Mexico, and Peru. Their collaboration with global health advocates and organizations aims to streamline approvals and access in high-burden regions. In low-income countries, Gilead has signed royalty-free licensing agreements with six generic manufacturers to produce affordable versions for 120 nations with high HIV incidence. Until generics are available, Gilead pledges to supply lenacapavir at cost for up to 2 million people, a move to bridge immediate access gaps. While this could reshape HIV prevention in resource-limited settings, the scale of need—1.3 million new infections annually—means generics must ramp up quickly. The strategy could strengthen Gilead’s reputation and market position in emerging markets, but it risks criticism if access falls short or if high-income market pricing fuels perceptions of inequity.

Stakeholder alignment and long-term impact:

Gilead’s access approach requires alignment across diverse players—governments, insurers, healthcare providers, advocacy groups, and patients. In the U.S., securing coverage from 75% of insurers within six months and 90% within a year could set a precedent for rapid adoption of innovative therapies. Globally, partnerships with generic manufacturers and health organizations could create a scalable model for future long-acting drugs. However, challenges like pricing backlash, as seen with other high-cost therapies, or systemic gaps in healthcare infrastructure could disrupt progress. For example, ensuring patients return for biannual injections requires robust outreach and education, particularly in communities with limited trust in healthcare systems. If successful, Yeztugo could redefine industry standards for equitable access, encouraging competitors to prioritize long-acting solutions and accelerating innovation in HIV prevention.

Competitive positioning and market dynamics:

Yeztugo’s approval positions Gilead ahead of competitors like ViiV Healthcare, whose Apretude requires injections every two months. The longer dosing interval gives Yeztugo a competitive edge, but Gilead must maintain momentum through effective access programs and potential future innovations, such as the once-yearly formulation in Phase 3 trials. The strategy’s focus on affordability and access could deter pricing pressures from generics or rivals, while also building loyalty among providers and patients. However, if insurers or governments push for lower prices, or if Apretude counters with discounts or improved efficacy, Gilead may need to adjust its pricing or access commitments to sustain market share.

Conclusion

Overall, Yeztugo’s approval could redefine HIV prevention and accelerate progress toward global epidemic control targets. Gilead’s multifaceted access strategy—blending insurance coverage, assistance programs, generic partnerships, and global filings—sets a bold foundation. Yet, its success will depend on navigating the dynamics of economic, logistical, and competitive challenges while delivering tangible public health gains. For details, refer to Gilead’s announcement on the FDA approval