Twice-yearly injections prevent HIV in another phase 3 trial
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Key takeaways:
- Only two people taking twice-yearly lenacapavir in a phase 3 trial acquired HIV.
- Gilead said it plans to submit global regulatory filings some time later this year.
Twice-yearly injectable lenacapavir for HIV prevention reduced HIV infections by 96% compared with background HIV incidence and demonstrated superiority over a once-daily pill for PrEP in a phase 3 trial, Gilead Sciences announced Thursday.
Topline results from the PURPOSE 2 trial showed lenacapavir prevented HIV acquisition in 99.9% of study participants, which included cisgender men, transgender men, transgender women and gender nonbinary people who have sex with men in seven countries, including the United States.
It was the second large phase 3 trial to demonstrate lenacapavir’s ability to prevent HIV when administered just twice per year. The first trial, PURPOSE 1, was conducted among adolescent girls and women in Africa.
Gilead said it plans to present additional data from PURPOSE 2 at a future conference, and that it expects to use data from the two trials to begin submitting global regulatory filings by the end of this year in the hope of launching the medication in 2025.
Lenacapavir is already approved by the FDA for the treatment of resistant HIV, but not for prevention. HIV prevention medication in the U.S. currently consists of daily oral pills and one injectable, ViiV Healthcare’s cabotegravir plus rilpivirine, which is administered every 2 months.
“The difficulty some people can experience with taking an oral pill every day, including challenges with adherence and stigma, have hindered uptake and persistence of the standard of care for too long, thus blunting PrEP’s impact on HIV prevention,” Onyema Ogbuagu, MBBCh, FACP, FIDSA, principal investigator on the PURPOSE 2 trial and associate professor of medicine and pharmacology at Yale School of Medicine, said in a press release.
“The incredible efficacy demonstrated in the PURPOSE 2 trial, the potential benefits of twice-yearly injection and the diversity of trial sites, and participants show the impact that lenacapavir for PrEP could have for people around the world who need new choices to reduce their changes of acquiring HIV,” Ogbuagu said.
In June, Gilead announced results from PURPOSE 1 that showed it prevented 100% of new HIV infections among cisgender women and adolescent girls at 28 trial sites in South Africa and Uganda. The medication was so successful that the trial was stopped early and lenacapavir was recommended for all study participants.
Full results from the trial were presented at the International AIDS Conference and published in The New England Journal of Medicine in July.
PURPOSE 2 is a phase 3, double-blind randomized study that included more than 3,200 cisgender men, transgender men, transgender women and gender nonbinary people aged 16 years and older who have sex with men at 88 trial sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the U.S.
Researchers randomly assigned study participants to either receive lenacapavir or Gilead’s daily PrEP medication, emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), at a 2:1 ratio. There was not a control group because a placebo would be unethical, Gilead said. Instead, researchers used background HIV incidence as the primary comparator to lenacapavir, and FTC/TDF as the secondary comparator.
Among 2,180 people who received lenacapavir, there were two incident cases of HIV (incidence 0.1 per 100 person-years), meaning 99.9% did not acquire the virus. In comparison, there were 2.37 infections per 100 person-years in the background HIV group, equaling a 96% risk reduction for HIV in the lenacapavir group. There were 0.93 infections per 100 person-years (nine cases among 1,087 people) in the FTC/TDF group, showing that the twice-year shot was 89% more effective than daily oral PrEP.
“This is the second impressive result for this new HIV prevention option, opening up more possibilities for choice for even more people to find an option that is right for them,” Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said in a press release, noting that an easier to follow regimen for HIV prevention will expand choice and could decrease the burden on health care systems already “stretched to the limit.”
Observers have raised questions about the potential cost of lenacapavir, and whether it could be a barrier to uptake. Gilead in July said it was “too early” to say how much the drug will cost as PrEP, and did not provide an estimate of the cost on Thursday.
“Gilead is committed to making lenacapavir available in the countries where the need is greatest, including expediting voluntary licensing partners to supply high-quality, low-cost versions of lenacapavir,” the company said Thursday. “Gilead is actively working to finalize these contracts.”
References:
- Gilead’s twice-yearly lenacapavir for HIV prevention reduces HIV infections by 96% and demonstrated superiority to daily Truvada in second pivotal phase 3 trial. https://www.gilead.com/news-and-press/press-room/press-releases/2024/9/gileads-twiceyearly-lenacapavir-for-hiv-prevention-reduced-hiv-infections-by-96-and-demonstrated-superiority-to-daily-truvada-in-second-pivotal-ph. Published Sept. 12, 2024. Accessed Sept. 12, 2024.
- Second pivotal trial of twice-yearly HIV prevention injection safe and highly effective: PURPOSE 2 trial among gay men, trans and nonbinary people. https://avac.org/press-release/purpose-2/. Published Sept. 12, 2024. Accessed Sept. 12, 2024.
- Updated statement on global access planning for lenacapavir for HIV prevention. https://www.gilead.com/news-and-press/company-statements/updated-statement-on-global-access-planning-for-lenacapavir-for-hiv-prevention. Published July 24, 2024. Accessed Sept. 12, 2024.
Perspective
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The times are changing! In the world of the HIV epidemic, that can be a very good thing.
Preventing new HIV infections has moved from strategies based on behavioral change — safe sex, for example — which were of limited long-term utility, to taking medications to prevent transmission. Effective control of HIV through treatment is very successful in blocking further spread, and oral antiretroviral medications used by uninfected persons as PrEP has also been an important and useful strategy.
Recently, HIV treatment and prevention has moved to long-acting injectable drugs. One these drugs, lenacapavir, was shown to be 100% effective in preventing new HIV infection in adolescent girls and women in the PURPOSE 1 trial when administered every 6 months.
A companion clinical trial, PURPOSE 2, assessed the same twice-yearly regimen among several thousand men at risk for HIV infection. The results of the study also show dramatic benefit, with only about one in 1,000 becoming infected, compared with almost 3% expected without PrEP.
Together, these results give promise in ending the HIV epidemic. If the costs can be minimized, and if efficient care systems can be implemented — both major challenges that demand immediate attention — the scourge of new HIV infection can be brought to an end. As we are approaching the 50th anniversary of the HIV era, we can only hope our society can find a way to reach that historic end.
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