Lenacapavir: Twice-yearly injectable medicine effective for HIV prevention—Research

Results from studies have shown the overwhelming efficacy of twice-yearly injections of Lenacapavir (LEN) in the prevention of HIV infections compared to standard oral preventive HIV medicines, known as pre-exposure prophylaxis (PrEP). Gilead’s landmark PURPOSE trials are evaluating the safety and efficacy of the investigational, twice-yearly injectable medicine, lenacapavir, to reduce the chance of getting […]

Results from studies have shown the overwhelming efficacy of twice-yearly injections of Lenacapavir (LEN) in the prevention of HIV infections compared to standard oral preventive HIV medicines, known as pre-exposure prophylaxis (PrEP).

Gilead’s landmark PURPOSE trials are evaluating the safety and efficacy of the investigational, twice-yearly injectable medicine, lenacapavir, to reduce the chance of getting HIV.

The Phase 2 and 3 program, consisting of PURPOSE 1-5, is assessing the potential of lenacapavir to help a diverse range of people around the world who could benefit from PrEP.

The results on the potential of lenacapavir for PrEP were first formally presented at the 25th International AIDS Conference (AIDS 2024) in Munich, Germany, in July 2024.

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The PURPOSE 1 trial results, presented at the conference, confirmed that lenacapavir gave 100% protection against HIV acquisition in cisgender women.

In the PURPOSE 2 trial, there were two HIV infections in the lenacapavir group, demonstrating that 99.9% of participants in the lenacapavir group did not acquire HIV infection and a 96% reduction in HIV infections compared to HIV among a broad and geographically diverse range of cisgender men and gender-diverse people.

PURPOSE 2 enrolled 3267 participants, including cisgender men, transgender men, transgender women, and gender non-binary individuals aged 16 and older, who have sex with partners assigned male at birth. The trial was conducted at 88 sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States.

Only two new HIV cases were recorded among 2,180 participants receiving LEN twice yearly, compared to nine new cases among the 1,087 participants receiving daily oral TDF/FTC (tenofovir disoproxil fumarate/emtricitabine).

The findings build upon the earlier results from the PURPOSE 1 trial, which demonstrated LEN’s efficacy in preventing HIV among cisgender women in sub-Saharan Africa, with zero infections among women receiving the injectable.

In both trials, twice-yearly lenacapavir also demonstrated superiority in the prevention of HIV infections when compared with once-daily oral Truvada. It was also generally well tolerated, with no significant or new safety concerns identified.

Presenting the results of the PURPOSE 1 trial during the conference, Linda-Gail, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and former President of the International AIDS Society, said, “These stellar results show that twice-yearly lenacapavir for PrEP, if approved, could offer a highly effective, tolerable, and discreet choice that could potentially improve PrEP uptake and persistence, helping us to reduce HIV in cisgender women globally.”

She said, “The PURPOSE 1 trial also sets a new standard for person-centered HIV prevention trials, demonstrating what can happen when a thoughtful scientific and community-focused trial design, a promising drug candidate, and an inclusive trial implementation plan come together.”

The immediate past IAS president, Sharon Lewin, said, “These data confirm that twice-yearly lenacapavir for HIV prevention is a breakthrough advance with huge public health potential. If approved and delivered—rapidly, affordably, and equitably—to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention. We all owe a debt of gratitude to the thousands of young women in South Africa and Uganda who volunteered to be part of this study.

Lewin, who was also the AIDS 2024 International Co-Chair and Director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia,  said, “Now we eagerly await results from PURPOSE 2, which is assessing twice-yearly lenacapavir for HIV prevention in other populations and countries. In the meantime, all stakeholders must work together to accelerate equitable delivery of existing HIV prevention options and do more to prepare for future options, such as lenacapavir for PrEP.”

The Joint United Nations Programme on HIV/AIDS (UNAIDS)’s  Executive Director Winnie Byanyima described Gilead’s twice-yearly injectable lenacapavir  for HIV prevention as a “miracle prevention tool” and provides hope of accelerating efforts to end AIDS.

The World Health Organization (WHO) said together, the results from PURPOSE 1 and PURPOSE 2 provide compelling evidence for the potential of LEN to transform HIV prevention globally, across diverse populations. It is important to note that oral PrEP is safe and effective in preventing HIV when taken as indicated. LEN’s twice-yearly dosing offers a significant advantage for people who face challenges with adhering to daily oral PrEP, including stigma and discrimination, pill fatigue, and challenges with consistent access to medication.

It said the addition of lenacapavir to the growing list of HIV prevention options, including oral PrEP containing TDF (2015), the dapivirine ring (DVR) (2021), and long-acting cabotegravir (CAB-LA) (2022), can expand the toolkit for global HIV prevention efforts, especially for regions and communities with high HIV incidence.

The organization had earlier welcomed the news that long-acting injectable lenacapavir as PrEP is highly effective in preventing HIV acquisition in women.

It said, “Women in countries where the PURPOSE 1 trial was conducted, and across East and southern Africa, continue to experience high HIV incidence. Additional effective and acceptable HIV prevention choices for women are needed, including PrEP choices.

“LEN has the potential to further increase the range of effective and acceptable prevention choices available to women, overcome challenges, including those related to the effective use of oral tablets, and improve uptake and use of prevention.”

However, one of the concerns raised at AIDS 2024 by activists is the pricing of lenacapavir and whether it would be simply too expensive for use in low- and middle-income countries, such as South Africa and Uganda, where it was tested among more than 5,000 women, including pregnant women and adolescents.

A study presented at AIDS 2024 had estimated that lenacapavir could be priced at USD 100 per person per year and subsequently USD 35-40, with research and development investment, scaled demand, and mass production of generic lenacapavir under voluntary licensing.

UNAIDS said it was concerned that Gilead’s latest statement regarding its access strategy for low- and middle-income countries mentions only “high-incidence countries and resource-limited countries” and makes no specific mention of upper-middle-income countries or the Medicines Patent Pool ( MPP). Upper middle-income countries account for 41% of new HIV infections and 37% of all people living with HIV. These countries are home to millions who cannot afford the prices Gilead charges high-income countries.

It called for a generic version of Lenacapavir to be licensed to all low- and middle-income countries through the MPP. In a letter coordinated by the People’s Medicines Alliance, it urged Gilead to allow generic production of Lenacapavir to all low- and middle-income countries by negotiating voluntary licensing agreements through the MPP. The MPP is a UN-backed program with extensive experience negotiating generics agreements between originators and generic pharmaceutical companies.

Executive Director of UNAIDS Winnie Byanyima said there was a need for Gilead to ensure that all people who need it can have access to this game-changing medicine.

She said, “The success of Gilead’s recent Lenacapavir trial is an exciting development. While we still await regulatory approvals, normative guidance, and results from the other ongoing trials, this news offers hope that we can enable everyone who would benefit, including especially the most marginalized communities, to have access to the help they need. Enabling equitable global access to new technologies can help get the world on track to end AIDS as a public health threat by 2030. “ However, it is concerning that Gilead’s latest announcement seems to mention neither upper-middle-income countries, where people cannot afford anything like Lenacapavir’s current $42,250 price tag, nor a commitment to work with the UN-backed Medicines Patent Pool. Without these safeguards, it cannot be assured that this game-changing medicine will reach all those who need it.”

Immediate past president of IAS, Sharon Lewin also said that, “breakthroughs in medicine are only meaningful when the people who need those medicines can access them.”.

On December 19, 2024, Gilead announced that the company completed New Drug Application (NDA) submissions to the U.S. Food and Drug Administration (FDA) seeking approval of an investigational use of lenacapavir for PrEP.

A statement from Gilead said the submission is supported by data from the Phase 3 PURPOSE 1 and PURPOSE 2 trials it conducted.

Earlier in October 2024, the FDA granted lenacapavir for PrEP Breakthrough Therapy Designation, which is intended to expedite the review of new drugs that may demonstrate substantial improvement over available therapy.

Gilead said it is executing an access strategy, informed by global health advocates and organizations, that prioritizes speed and enables the most efficient paths for the regulatory review, approval of, and access to  lenacapavir for PrEP in regions around the world.