Lenacapavir poised to ‘transform’ HIV prevention
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Key takeaways:
- Twice-yearly lenacapavir injections reduced HIV infections by 96% in a phase 3 trial.
- Gilead Sciences will begin regulatory filings for the long-acting medication this year.
LIMA, Peru — Positive data continue to roll in for lenacapavir, the long-acting injectable that looks like a game-changer for HIV prevention.
Researchers presented findings at the HIV Research for Prevention conference that were originally publicized by Gilead Sciences in September, which showed that lenacapavir — administered just twice per year — reduced HIV infections by 96% in a gender-diverse population and outperformed oral daily PrEP in the phase 3 PURPOSE 2 trial.
According to new details reported for the first time at the conference, adverse reactions to the injections were rare and did not cause significant discontinuations of the medication.
An earlier phase 3 trial, PURPOSE 1, showed that lenacapavir prevented 100% of new HIV infections among adolescent girls and women, a population commonly overlooked in HIV medication trials.
There are multiple other PURPOSE trials underway to assess lenacapavir in even more populations, including people who inject drugs.
“Lenacapavir for PrEP has the potential to transform — together with other agents — the global HIV prevention landscape for people of all genders,” International AIDS Society President Beatriz Grinsztejn, MD, PhD, director of the HIV/AIDS clinical research unit at the Evandro Chagas National Institute of Infectious Diseases in Rio de Janeiro, said at a press conference here.
Questions of cost, access
A vaccine has long been the holy grail of HIV prevention research. But with the recent high-profile failures of multiple investigational HIV vaccines, long-acting injectables have emerged as an option for prolonged protection. In contrast to oral PrEP, which is highly effective but must be taken every day, people on injectable medication remain protected for months between shots.
ViiV Healthcare’s cabotegravir, which is administered every 2 months, is already approved by the FDA for HIV prevention in the United States. Lenacapavir is also approved in the U.S., but as treatment for resistant infections, not prevention. Gilead said it plans to begin regulatory submissions to get lenacapavir approved for prevention by the end of the year.
As is often the case with new HIV medications, questions about cost and access to lenacapavir remain. Gilead has not said what the antiretroviral will cost as PrEP. As treatment for highly resistant HIV, the medication costs more than $42,000 per year in the U.S.
Gilead made good on a promise to expand global access to lenacapavir by signing royalty-free agreements with six pharmaceutical companies — three in India, one in Egypt, one in Pakistan and one in the U.S. — that will allow the manufacturers to make generic versions of lenacapavir for 120 countries with a high incidence of HIV but limited resources. The plan will prioritize 18 countries that account for around 70% of new infections, Gilead said.
In a statement, the IAS applauded the decision but said it did not go far enough, warning that it “still leave(s) out millions around the world.”
“This will substantially reduce the time to market,” the IAS said of the agreements. “However, many countries with high HIV incidence are not included in the licensing arrangements, which will slow access.”
One of the countries that will not get access to generic lenacapavir is Peru, this year’s HIVR4P host, despite being one of the seven countries that participated in the PURPOSE 2 trial.
New data
The trial assessed the effectiveness of lenacapavir among cisgender men, transgender men, transgender women and gender nonbinary people who have sex with men.
As it did in the previous trial, lenacapavir prevented almost all new HIV infections in PURPOSE 2 — there were only two recorded among the more than 2,100 participants who received lenacapavir.
According to the researchers, the result was a 96% reduction in new HIV infections compared with background HIV incidence — the number of new infections that would have been expected to occur among participants in the absence of lenacapavir. (The trial did not have a traditional control group because offering participants a placebo would not have been ethical, Gilead said.)
The trial did compare lenacapavir to emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), Gilead’s daily oral pill for HIV PrEP, assigning participants in a 2:1 ratio to receive either the injectable or FTC/TDF. There were nine new HIV cases among nearly 1,100 participants in the FTC/TDF arm, making lenacapavir 89% more effective than daily oral PrEP, according to the researchers.
“Lenacapavir represents a novel, highly effective tool for prevention and is not dependent upon daily oral adherence,” PURPOSE 2 investigator Colleen Kelley, MD, MPH, a professor of medicine in the division of infectious diseases at Emory University School of Medicine, told reporters at HIVR4P.
According to Kelley, more than 15,000 injections of lenacapavir were delivered in PURPOSE 2. Adherence data for the trial have not been announced, but more than 90% of participants in PURPOSE 1 received their injections on time. Out of the 29 study participants who withdrew from the trial because of injection site reactions, 26 were in the lenacapavir arm, Kelley said.
“For some people, the injection site reactions will be a challenge for adherence. So far, it appears that it does not contribute in a significant way to discontinuations, but there’s more [work] to do to understand injection site reactions in the trial,” Kelley said. “That’s one area where we might see challenges” with adherence.
‘How will we keep people engaged?’
Lenacapavir is given in two injections that have to be delivered subcutaneously, something that “takes training and time” to learn, National Institute of Allergy and Infectious Diseases Director Jeanne M. Marrazzo, MD, MPH, told reporters here.
Another clinical concern, Kelley said, is getting patients to continue coming back for their shots.
“We’ve never had a 6-month product. I don’t think we have any idea how that will be implemented over the long term in our clinical spaces,” Kelley said. “How will we keep people engaged when we don’t have to engage them that much?”
References:
- Gilead presents additional efficacy, safety and demographic data from PURPOSE 2 trial at 5th HIV Research for Prevention Conference. https://www.gilead.com/news/news-details/2024/gilead-presents-additional-efficacy-safety-and-demographic-data-from-purpose-2-trial-at-5th-hiv-research-for-prevention-conference. Published Oct. 7, 2024. Accessed Oct. 7, 2024.
- Gilead signs royalty-free voluntary licensing agreements with six generic manufacturers to increase access to lenacapavir for HIV prevention in high-incidence, resource-limited countries. https://www.gilead.com/news/news-details/2024/gilead-signs-royalty-free-voluntary-licensing-agreements-with-six-generic-manufacturers-to-increase-access-to-lenacapavir-for-hiv-prevention-in-high-incidence-resource-limited-countries. Published Oct. 2, 2024. Accessed Oct. 6, 2024.
- IAS statement: IAS calls for global access as Gilead announces lenacapavir licensing. https://www.iasociety.org/ias-statement/ias-calls-global-access-gilead-announces-lenacapavir-licensing. Published Oct. 3, 2024. Accessed Oct. 6, 2024.
- New HIV drug can only offer hope of ending AIDS if all have access, UNAIDS says. https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2024/july/20240710_lenacapavir. Published July 10, 2024. Accessed Oct. 7, 2024.
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