Science magazine has chosen twice-yearly lenacapavir PrEP as its 2024 Breakthrough of the Year, recognizing it as a game-changer in the fight to end the global HIV epidemic. Looking ahead, once-yearly HIV prevention injections could be on the horizon, Gilead Sciences executives said at a December 10 analyst and investor event.
The drug, however, is not yet approved for HIV prevention by federal regulators, though that could occur in 2025, Gilead officials said.
This is the third time Science has chosen an HIV/AIDS intervention as its annual breakthrough. In 1996, it cited protease inhibitors, a new class of drugs that ushered in effective combination antiretroviral therapy. In 2011, it recognized the groundbreaking HPTN 052 trial, which showed that effective treatment dramatically reduces sexual transmission of HIV.
"Science acknowledges the next, but by no means final, step in the drive to fight AIDS, where the rigors of the laboratory and the needs of humanity are inseparable," editor in chief Holden Thorp wrote in an editorial.
Effective for women and gay men
The U.S. Food and Drug Administration approved the first PrEP regimen — once-daily Truvada pills (tenofovir disoproxil fumarate/emtricitabine) — in 2012, but biomedical HIV prevention has not reached its full potential. Only around a third of the 1.2 million people who could benefit from PrEP are using it, according to the Centers for Disease Control and Prevention.
Daily Truvada and Descovy (tenofovir alafenamide/emtricitabine), both from Gilead, are around 99% effective when taken consistently, but other options are still needed. Some people have trouble remembering to take a pill every day, feel stigma around using antiretrovirals that are also used to treat HIV, or may be hesitant to have pill bottles that could be lost or stolen. Currently, ViiV Healthcare's Apretude (injectable cabotegravir), which is administered by a health care provider every other month, is the longest-acting approved PrEP option.
Gilead's lenacapavir is an HIV capsid inhibitor that is injected under the skin and forms a long lasting "depot" that slowly releases the drug over time. It is currently only approved as part of a combination treatment regimen for people with multidrug-resistant virus, but FDA approval for HIV prevention could come as soon as next summer, according to Gilead.
The pending PrEP approval is supported by results from two large phase 3 trials showing that twice-yearly lenacapavir significantly reduced the risk of HIV acquisition in different at-risk populations.
As the Bay Area Reporter previously reported, the PURPOSE 1 trial, first presented at the International AIDS Conference this summer, showed that lenacapavir injections every six months were 100% effective for young cisgender women in Africa. The injections significantly reduced HIV incidence compared with the background rate and were superior to daily Truvada pills.
Likewise, the PURPOSE 2 study, presented at the HIV Research for Prevention Conference in October, showed that twice-yearly lenacapavir injections reduced the risk of HIV acquisition by 96% relative to the background incidence and by 89% compared to Truvada for gay and bisexual men and transgender and nonbinary people in the United States and six other countries. In both trials, lenacapavir was safe and generally well-tolerated.
While these results are groundbreaking, researchers, advocates and global health officials stress that the promise of twice-yearly PrEP can only be realized if it is widely accessible and affordable to everyone who needs it worldwide.
Lenacapavir for HIV treatment currently costs around $4,000 per month, but a recent analysis found that the price could potentially be brought down to around $40 per year with voluntary licensing and competition between generic suppliers. Gilead announced in October that it will work with pharmaceutical manufacturers to produce and sell generic lenacapavir for PrEP in more than 100 resource-limited countries with high HIV incidence.
Longer-acting PrEP
Despite its long duration, lenacapavir is an antiretroviral drug that blocks HIV replication, not a vaccine that trains the immune system to recognize and attack the virus. All traditional HIV vaccine candidates have failed in large trials, so long-acting PrEP is the next best thing.
The Science article about the breakthrough designation notes that the basic science underlying lenacapavir PrEP could have broader applications. Other viruses have their own capsid proteins, which form a shell around their genetic material, and capsid inhibitors might one day be used to fight other viral diseases. Similarly, although there is still no HIV vaccine, investments in HIV vaccine research over the years paved the way for COVID-19 vaccines and other advances.
Aiming to push the envelope further, Gilead is now developing even longer-acting PrEP candidates. At the December 10 meeting, Dr. Moupali Das, Gilead's vice president of clinical development for HIV prevention and pediatrics and a PURPOSE 1 trial investigator, said the company is working on injectable formulations of lenacapavir that could potentially be given annually. It is also testing a monthly oral lenacapavir prodrug (GS-3107) that could be the longest-acting PrEP pill.
A recently completed pharmacokinetics study suggested that once-yearly lenacapavir injections are feasible and appear to maintain adequate drug levels in the body. Phase 3 trials will begin soon, and data could be available for FDA review in 2027.
"At Gilead, we will not stop innovating until HIV is conquered," Dr. Jared Baeten, Gilead's senior vice president for clinical development and virology therapeutic area head, told the B.A.R. "By developing additional modalities and durations of PrEP, Gilead seeks to empower more individuals to choose, initiate and stay on the PrEP regimen that fits best into their lives."
Never miss a story! Keep up to date on the latest news, arts, politics, entertainment, and nightlife.
Sign up for the Bay Area Reporter's free weekday email newsletter. You'll receive our newsletters and special offers from our community partners.
Support California's largest LGBTQ newsroom. Your one-time, monthly, or annual contribution advocates for LGBTQ communities. Amplify a trusted voice providing news, information, and cultural coverage to all members of our community, regardless of their ability to pay -- Donate today!