Lenacapavir: a giant step forward in HIV prevention—but a missed opportunity for achieving equity and access
BMJ 2024; 387 doi: https://doi.org/10.1136/bmj.q2254 (Published 14 October 2024) Cite this as: BMJ 2024;387:q2254This year has seen a double dose of optimism in the field of HIV prevention. First, on 20 June 2024, came the results of the Purpose-1 trial in South Africa and Uganda.1 This randomised controlled trial found that twice yearly injection of the drug lenacapavir for pre-exposure prophylaxis (PrEP) was 100% effective at preventing HIV infection in cisgender women and was superior in efficacy to oral PrEP.2
Then, on 12 September 2024, came an interim analysis of another randomised controlled trial , the Purpose-2 trial, conducted in Argentina, Brazil, Mexico, Peru, Thailand, and the United States (US), which enrolled cisgender and transgender men, transgender women, and gender non-binary individuals who have sex with partners assigned male at birth. In this second trial, lenacapavir for PrEP reduced the risk of HIV infection by 96% and was again superior in efficacy to oral PrEP.3
Taken together, the World Health Organization said that the trials provide “compelling evidence for the potential of lenacapavir to transform HIV prevention globally, across diverse populations.”3 Of course, such a transformation will only be possible if lenacapavir (a twice yearly injectable) becomes readily available and affordable in all countries, especially those where HIV incidence is highest.
Since the trial results were made public, all eyes have been on Gilead—the company that makes and owns the patent on lenacapavir—to see what steps it would take to support equitable global access. In the US, Gilead charges around $44 000 per patient per year for lenacapavir treatment4—a price that is unaffordable to low and middle income countries. In stark contrast, the generically manufactured lenacapavir is estimated to cost $40-100 per person per year.4 When the Purpose-1 trial results were announced, Gilead promised to “provide a public statement regarding its planned access approach for high incidence, resource limited countries, which are primarily low and lower middle income countries.”5
Last week, Gilead made its highly anticipated public statement. The company has signed voluntary licensing agreements with six drug companies who will make and sell generic lenacapavir to an approved list of 120 countries.6 Although this is a highly welcome step—one that will hopefully drive access to the drug in the 120 nations approved by Gilead—we think that the company missed an important opportunity to invest in drug manufacturing in sub-Saharan Africa, where HIV incidence is highest. It also missed out an important group of middle income countries: Argentina, Brazil, Mexico, and Peru. Given Gilead’s access plan, is it churlish to highlight these misses? We do not think so: our aim is to point to a more robust, sustainable way to ensure global access to lifesaving medicines.
A missed opportunity
Of the six generic manufacturers selected, four are in India, one is in Pakistan, and one is in Egypt.6 Not a single manufacturer from sub-Saharan Africa was included. Even though the Purpose-1 trial was conducted in South Africa and Uganda, these countries will have to buy the drug from abroad, and the communities who participated in the trials might not have access to it. Gilead missed a great opportunity to invest in and strengthen local manufacturing in the region where its trial was conducted and in countries with the highest burden of HIV. It could have been a chance to link trial sites to manufacturing sites and to help boost self-sufficiency in the supply of a critical health commodity.
Sub-Saharan Africa is undergoing a revolution in pharmaceutical manufacturing, ramping up its capacity to make medicines, vaccines, and diagnostics.7 A slew of new initiatives have been launched, from modular manufacturing plants to the new Partnership for African Vaccine Manufacturing, which aims “to make the African continent self-sufficient in vaccine research, development, manufacturing, regulation, and delivery.”8 Private, public, and philanthropic investors in global health should be supporting this revolution, including by ensuring that nations where trials are conducted are also making the products tested in their communities.
It is encouraging to see that some global health funders, like the US President’s Emergency Plan for AIDS Relief (PEPFAR) and Gavi, the Vaccine Alliance, are taking action. PEPFAR has promised to help “accelerate regional manufacturing of critical health commodities” in sub-Saharan Africa by procuring 15 million HIV tests produced by African manufacturers in 2025 and by shifting “at least two million clients on firstline antiretroviral treatments to use African-made products” by 2030.9 Through a new African Vaccine Manufacturing Accelerator, Gavi has committed $1bn to support vaccine manufacturing in sub-Saharan Africa.10 We hope Gilead will expand its partnerships to include generic manufacturers in the sub-Saharan Africa region.
A missed group of countries
It is also concerning to see that Gilead has included an anti-diversion clause in its plan, which bans the generic manufacturers from selling the drug to middle income countries that are not on the list of 120 approved nations. This provision means that Argentina, Brazil, Mexico, and Peru are banned from buying generic versions of lenacapavir—all countries where the company tested its drug.11 We understand why Gilead instituted this clause—it wants to sell lenacapavir to these and other middle and high income countries at a cost higher than the cost of the generic version11—but the clause seems both punitive and extractive. Gilead chose these four countries for its Purpose-2 trial based on their HIV incidence, especially in sexual and gender minorities. A recent seroincidence study of sexual and gender minorities in Brazil and Peru, for example, found an annualised HIV incidence rate of 2.62% in Brazil (95% confidence interval 1.78% to 3.43%) and 6.69% in Peru (4.62% to 8.69%).12
Gilead says that it will provide lenacapavir to the trial participants until the drug becomes available in these countries,11 but this alone is not a national access plan and it will do too little to help reduce the HIV incidence in these countries. Surely countries that agreed to participate in testing for a company’s drug must be assured of access to the fruits of that research.
The ban is a very good example of what the Lancet Commission on Investing in Health called the “middle income dilemma.” Over 70% of those living under the poverty line now live in middle income countries (including a quarter of Brazil’s population). Yet the gross national income per capita of many of these countries disqualifies them from receiving health aid from aid donors and disqualifies them from getting lower drug prices from multinational companies.13 The “dilemma” is that these nations are not wealthy enough to afford the prices that high income countries pay. Tackling the middle income dilemma has become one of the most urgent, pressing imatters in the United Nations’ goal of ending AIDS by 2030.
Footnotes
Competing interests: GY declares research funding from the following organisations that fund HIV research or service delivery: the World Health Organization, the Gates Foundation, the Carnegie Corporation of New York, the UN Economic and Social Commission for Asia and the Pacific, and the Economic and Social Research Council. He is a member of the PEPFAR financing and sustainability committee and is co-chair of the Economics and Finance Working Group of the Partnership for Maternal, Newborn, and Child Health. SM declares she has no competing interests.