Urgency of planning broad vaccine-like access to lenacapavir PrEP globally
13 October 2024. Related: Conference reports, Treatment access, HIV prevention and transmission, R4P 2024 Lima.
Simon Collins, HIV i-Base
An impressive and timely plenary talk by Sharonann Lynch from Georgetown University’s O’Neill Institute showed the urgency of planning for global access to scientific advances in LMICs, notably lenacapavir for PrEP, in order to learn from the recent approaches to oral PrEP. [1]
This involves planning broad vaccine-like access programmes for lenacapavir where ambitious volumes and large scale commitments would secure the lowest entry prices for generic formulations. The planning needs to start now, during the two-year window expected for regulatory approval, WHO prequalification, and manufacturing scale up.
Drug pricing
Price is clearly a key factor in access, and two different research groups using established and proven methodology have already calculated that lenacapavir could be produced at an annual price of $41 per person. And even without a proposed initial price, the history with ART, oral PrEP, HCV and drug-resistant TB drugs has proven that pricing is dynamic and that generic competition and economies of scale will steadily reduce generic prices. [2, 3, 4]*
Over 25 years the annual per person prices of ART dropped from $10,000 for early combinations to less than $50 for the current WHO first-line combination of TLD (tenofovir/lamivudine/dolutegravir). Similarly, over the last 15 years, generic competition and wider use dropped the annual price for oral PrEP by 80% from roughly $270 to only $60 per person. More ambitious early targets however could have secured the lower price much earlier.
Generic pricing depends on securing at least medium scale volumes and on donors covering start-up costs. Importantly, the $41 price projected for lenacapavir, based on demand at 10 million doses, includes the cost of active pharmaceutical ingredients (API), excipients, manufacturing, distribution, profit and tax. This might even be a conservative minimum price that in practice could turn out to be even lower.
However, the projected lenacapavir price of US$41 a year is also only an aspirational future price that depends on government and donors guaranteeing significant and stable orders for several years. It takes both time and investment to scale up manufacturing and so the next two years need to be planned using much more ambitious targets than were used for oral PrEP.
Lenacapavir is probably the most important single development that could significantly reduce the HIV curves and it demands an exceptional approach to access if this opportunity is not to be wasted. Anything less, and the incredible scientific advances that it brings will be “stuck at the borders” of countries most in need, which as community, is not acceptable.
Community demand and the timeline for access
Ambitious community demands are needed to drive global access to lenacapavir.
This is because our previous ambitious demands over access to treatments, which appeared impossible to many, actually got us to the current success. There are now over 24 million people globally on ART, and we achieved similarly impressive price reductions for generic PrEP, TB and HCV drugs.
The timeline is also important. Gilead has committed to submitting lencapavir to regulatory agencies for PrEP before the end of 2024 and a six-month review will make branded lenacapavir available in some countries by mid 2025. Generic companies then applying for FDA prequalification and WHO review might take another year, which means that generic lenacapavir might be available by Q3 2027.
This time could be used to include generic lenacapavir in country applications to the Global Fund for grant cycles 7 or 8.
Demanding a transformational price
However, projected volumes that are only based on the current “mediocre pace of scale-up” of only having 2.9 million people on PrEP by 2027 and only 3.4 million by 2030 will not be enough to impact on negotiations to reduce the launch price of lenacapavir. “Donors are already making the mistake of underestimating demand for lenacapavir based on their experience for oral PrEP which risks becoming a self-fulfilling prophecy”. Starting with low expectations will only generate a price which will likely be too high to include in proposals to the Global Fund.
Instead, we need to propose a transformational price. We need to mobilise US$250 million funding now to lock in a per person price of US$50 in two years’ time when generic companies will enter the market.
Access for countries in the PURPOSE studies
We also need to make sure this will cover concentrated epidemics in all countries, including Argentina, Brazil, Mexico and Peru, which are currently excluded from Gilead’s proposed voluntary licensing programme for generic lenacapavir, even though they contributed clinical trial sites in PURPOSE 2.
These countries provided participants and results that will enable lenacapavir registration. One of the principles of the Helsinki Declaration, designed to ensure ethical research, upholds that vulnerable people and groups need to be able to benefit from any new treatments that are subsequently approved. This should cover people in low-income countries, many of who are already marginalised, from being exploited for cheaper research. The Helsinki principles should cover the wider population of low- and miffle-income countries, not just study participants. [6]
Broad access over limited target programmes
Rationing eligibility in access programmes will only produce a slow drip effect that risks stigmatising lenacapavir and the people who do get to use it. This has been the experience with oral PrEP, where in an analysis of 120 countries, most limited access to one or two groups, often just gay and bisexual men and excluded most key populations such as sex workers, people who are transgender and people who inject drugs. From 2013-2023 nearly 18 million people newly accessed ART compared to the squandered missed opportunity where only 6 million people during the same period accessed PrEP. The mediocre approach to PrEP resulted in an annual launch price for generic oral PrEP at US$116 per person in 2020 rather than the $40 now achieved.
A recent analysis from CHAI estimates that at an affordable price, injectable PrEP could easily triple use of PrEP by 2030 compared to the current status quo.
Public health systems need to be strengthened to deliver increased PrEP based on rights-based access and to set national targets that make PrEP available from all public clinics. Population-based benefits from 6-monthly injectable PrEP only come with broader and wider use among the general population, not from trying to micro-target individuals defined as high risk. This is the only approach that will reach the significant number of new infections occurring in people who are not currently covered because of the restriction of oral PrEP to people defined as being at high risk. The vaccine-like protection provided by a 6-monthly formulation needs a vaccine-like programme for access. [7]
Ambitious targets and funding
Reaching global 2025 targets will involve reducing new infections by almost 50% each year rather than the 3-4% annual reductions seen from 2015 to 2023 and this will involve supporting a minimum of 21 million people to access PrEP in 2025.
The additional funding for this involves expanding overall funding for HIV and allocating a greater percentage of funding towards PrEP.
The urgency of international agencies collaborating to enable this goal is highlighted by the data showing that 250,000 people newly seroconverted in the few months since the PURPOSE 1 results were reported, half of whom were adolescent and young women. Every year half a million people still die of AIDS and people already marginalised and criminalised within their own countries are not going to magically have better access to HIV treatment than HIV prevention.
This involves broad support to collectively agitate, advocate and advance this ambitious agenda that could limit HIV to our generation rather than perpetuate it to the next.
*All references to price in this article are in US$.
comment
The PURPOSE 1 and 2 studies have already shown that demand for 6-monthly injectable PrEP is popular because 6-8% of participants were already HIV positive at screening and then brought into care. This itself significantly reduces future HIV transmission by reducing population viral load. More frequent testing is a key component of combination prevention that together with rapid ART and oral PrEP has already reduced HIV transmission in many high-income countries.
The incredibly high retention rate in the AMP studies over many years showed that in contrast to oral PrEP, injectable options are highly acceptable.
Continued access to lenacapavir in open-label extensions to the PURPOSE studies is also likely to further increase community demand during the next two years needed for broad generic access.
It would also help to prioritise broad access in a demonstration country to show the impact on HIV incidence when rapid population coverage is available.
References
- Lynch S. From trials to policies and product access: how can we do better?
https://hivr4p2024.iasociety.org/cmVirtualPortal/_iasociety/hivr4p2024/session/0000063660/22e0cf841f3370e7ec52467772aa35681e7fb80f/0000000060 - Pinheiro Edos S et al. A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations. Antiviral Res. 2008 Sep;79(3):143-65. doi: 10.1016/j.antiviral.2008.05.001. (2 June 2008).
https://pubmed.ncbi.nlm.nih.gov/18571246/ - CHAI. Cost of Goods Sold (COGS) Analysis: Generic Long-Acting Injectable Cabotegravir (CAB-LA). (February 2023).
https://www.clintonhealthaccess.org/wp-content/uploads/2022/10/Generic-CAB-LA-COGS-Analysis.pdf - Hill A et al. Lenacapavir to prevent HIV infection: current prices versus estimated costs of production. Journal of Antimicrobial Chemotherapy, 2024; dkae305. (3 September 2024).
- Wu L et al. Health impact, budget impact, and price threshold for cost-effectiveness of lenacapavir for HIV pre-exposure prophylaxis in eastern and southern Africa: a modelling analysis. The Lancet HIV. (20 September 2024).
https://doi.org/10.1016/S2352-3018(24)00239-X