Twice-yearly shot proves successful at preventing HIV among women in Phase 3 study

The twice-yearly injection of the drug lenacapavir can provide total protection against HIV infections, demonstrating 100% efficacy in Phase 3 trial data released by drugmaker Gilead and published Wednesday in the New England Journal of Medicine.

For years, most people have taken prevention tools known as PrEP, such as a daily pill called Truvada to prevent infections of the human immunodeficiency virus or HIV.

More recently, some people have received regular injections of the drug Apretude – two shots administered one month apart then every two months thereafter – to reduce their risk of HIV.

The twice-a-year injections of lenacapavir could add another option at preventing HIV infections to the toolbox.

Among more than 5,000 women and adolescent girls participating in the trial in Africa who were HIV negative, none of the participants who received twice-yearly lenacapavir acquired HIV infection during the course of the study, according to the results which were also presented at the International AIDS Conference in Munich.

“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,” Linda-Gail Bekker, director of the Desmond Tutu HIV Center at the University of Cape Town in South Africa, and former President of the International AIDS Society, said in a news release.

The study, called the PURPOSE 1 trial, involved adolescent girls and young women in South Africa and Uganda who were randomly assigned to either receive lenacapavir injections every 26 weeks or daily HIV medications – either emtricitabine–tenofovir alafenamide or emtricitabine–tenofovir disoproxil fumarate – in pill form. It was a double-blind study, and the participants did not know which group they were in.

Many of the women and girls who received lenacapavir, about 69%, experienced reactions at the injection site compared with 35% in the placebo injection group, but no safety concerns were found, according to the researchers.

Among the women and girls, the researchers assessed how many HIV infections occurred over 26 weeks, and 55 infections total were observed: zero in the lenacapavir group, 39 in the daily emtricitabine–tenofovir alafenamide group and 16 in the daily emtricitabine–tenofovir disoproxil fumarate group.

‘An important advance for the field’

The finding of lenacapavir having 100% efficacy for HIV prevention in women “is an important advance for the field, and I think that the field will welcome it as an additional prevention option,” said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.

“But I do think it’s important to realize that these data are only in prevention in young women. There is another study that’s still ongoing, that hasn’t been read out yet, in men,” he said. “So, we await more data to learn about the prevention efficacy in men as well.”

Multiple clinical trials involving lenacapavir are ongoing. The latest Phase 3 findings are part of Gilead’s PURPOSE program, which comprises five HIV prevention trials around the world.

“We are eagerly awaiting the results of the other studies, which enrolled other populations, including men who have sex with men and are disproportionately vulnerable to HIV,” Dr. Jason Zucker, assistant professor of medicine at Columbia University Irving Medical Center, who was not involved in the trial, said in an email.

Barouch also was not involved in the latest Phase 3 trial, nor the newly launched US trials, but he previously studied lenacapavir as a drug to prevent simian–human immunodeficiency virus infections in preclinical animal studies, which he said ultimately predicted how the drug would later behave as an HIV-prevention tool in humans.

People who already take either daily PrEP pills or regular PrEP injections to prevent HIV may benefit from having lenacapavir available to them as another option, Barouch said.

“This is a very good option that is very convenient because it can be given only once every six months,” he said. “I think for people who are at high risk, who are not yet on PrEP, it’s an option because it provides a more convenient option, if that was the reason why they were not interested in PrEP beforehand.”

Lenacapavir is not approved for HIV prevention anywhere in the world, but as it continues to be studied as a pre-exposure prophylaxis drug to prevent HIV infection, questions abound around cost.

“We know that the drug is efficacious in cisgender women and appears safe with all the data we have,” Zucker said in the email. “My primary worry is around implementation; these drugs are often expensive after approval and those costs can serve to limit access and exacerbate disparities instead of alleviate them.”

Lenacapavir is already approved by the US Food and Drug Administration for the treatment of HIV infection in adults, in combination with other HIV antiretroviral medicines, and it’s estimated to cost more than $40,000 in a year as a manufacturer’s list price, or around $39,000 annually, as an average wholesale price.

Separate research presented Tuesday at the AIDS Conference in Munich suggests that the production of a generic version of lenacapavir could cost under $100 per person.

The team of researchers – from the United Kingdom, Germany and the United States – projected what the minimum pricing of lenacapavir could be, based on the drug’s current ingredients, production models and cost models. The researchers demonstrated that lenacapavir could be mass-produced for up to $93 per person per year, potentially falling to about $40 per person per year.

“While Gilead awaits additional phase 3 clinical trial data and the potential regulatory filings for HIV prevention administered twice-yearly, it is too early to state the price of lenacapavir for PrEP (prevention). Our pledge is to price our medicines to reflect the value they deliver to people, patients, healthcare systems and society,” a Gilead spokeperson said in an emailed statement Tuesday.

“In view of the company’s ongoing commitment to communities affected by HIV, we have been developing a strategy to enable broad, sustainable access globally,” the statement said in part. “A key component of this strategy is to deliver lenacapavir swiftly, sustainably and in sufficient volumes, if approved, to high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.”

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In late May, hundreds of activists wrote a letter to Gilead CEO Daniel O’Day urging the company to ensure that people in low- and middle-income countries have the same access to lenacapavir as an HIV medication as do people in high-income countries.

“Requiring only two injections a year, it could be a real game-changer worldwide for the people most excluded from high quality healthcare. We urge Gilead to ensure that people in the Global South living with or at risk of HIV can access this groundbreaking medicine at the same time as people in the Global North can,” said the letter, released by the People’s Medicines Alliance, a global coalition focused on improving access to medicines.

“We request that you license Lenacapavir now, without delay, through the Medicines Patent Pool and make the license open to all low- and middle-income countries,” the letter said in part. “With Lenacapavir approved in the US and Europe for treatment, and likely to soon be available for prevention, there is no reason to delay the sharing of this technology.”

The ongoing clinical trials involving lenacapavir could potentially provide another effective option for HIV prevention in men, building upon the drug's 100% efficacy in preventing HIV infections seen in cisgender women. The cost of lenacapavir as a prevention drug is a significant concern, with estimates suggesting it could be produced for as low as $40 per person per year in resource-limited countries.