By IDSE News Staff
The results of an interim analysis from a second pivotal phase 3 clinical trial investigating the use of Gilead’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, found that it reduced HIV infections by 96% compared with background HIV incidence (bHIV).
There were two incident cases among 2,180 participants, corresponding to 99.9% of participants not acquiring HIV infection in the lenacapavir group. Twice-yearly lenacapavir also demonstrated superiority to once-daily emtricitabine and tenofovir disoproxil fumarate (F/TDF).
The PURPOSE 2 trial (ClinicalTrials.gov Identifier: NCT04925752), a phase 3, multicenter, randomized double-blind study, is evaluating the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP versus once-daily oral F/TDF and bHIV in more than 3,200 cisgender men, transgender men, transgender women and gender non-binary individuals ages 16 years or older who have sex with partners assigned male at birth. There were 88 trial sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.
Study participants were randomized in a 2:1 ratio to lenacapavir and F/TDF, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and F/TDF as a secondary comparator.
There were two incident cases among 2,180 participants in the lenacapavir group (0.10 per 100 person-years), so 99.9% of participants did not acquire HIV in the lenacapavir group. The results demonstrated superiority of twice-yearly lenacapavir over bHIV (2.37 per 100 person-years), with a 96% relative risk reduction (incidence rate ratio, 0.04; P<0.0001). There were nine incident cases among 1,087 individuals in the F/TDF group (0.93 per 100 person-years). Twice-yearly lenacapavir was 89% more effective than once-daily F/TDF (incidence rate ratio, 0.11; P=0.00245). In the trial, lenacapavir and Truvada were generally well tolerated, and no significant or new safety concerns were identified.
At the interim analysis, the independent data monitoring committee confirmed that the PURPOSE 2 trial met its key efficacy end points of superiority to both bHIV and once-daily oral F/TDF for PrEP. Therefore, the committee recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants.
“In the United States, the stubbornly high rate of HIV diagnoses—especially in the U.S. South, and particularly among gay and bisexual men of color and transgender people—demands novel approaches to help people prevent HIV acquisition,” said Colleen Kelley, MD, MPH, a professor of medicine at Emory University, in Atlanta, and a PURPOSE 2 principal investigator.
“Because adherence to oral products can be challenging for some people, twice-yearly injectable lenacapavir for PrEP has the potential to be one of the most impactful interventions we could have to drive down new infections and bring us closer to ending the HIV epidemic in the United States,” Dr. Kelley said.
This is the second pivotal phase 3 trial to demonstrate superior efficacy of twice-yearly lenacapavir for investigational use for HIV prevention as PrEP. In June 2024, the PURPOSE 1 trial, studying lenacapavir for PrEP among cisgender women in sub-Saharan Africa, also was unblinded early because it met its key efficacy end points.
The data from the PURPOSE 1 and PURPOSE 2 trials will support upcoming regulatory filings for approval of twice-yearly lenacapavir for PrEP, Gilead said.
More detailed data from PURPOSE 2 will be presented at a future conference.
“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,” said PURPOSE 2 principal investigator Onyema Ogbuagu, MBBCh, FACP, FIDSA, an associate professor of medicine and pharmacology at Yale School of Medicine and the director of the Yale Antivirals and Vaccines Research Program, in New Haven, Conn. “The incredible efficacy demonstrated in the PURPOSE 2 trial, the potential benefits of a 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 chances of acquiring HIV. This breakthrough adds significantly to our arsenal of tools to move us closer to achieving an AIDS-free generation.”
