Twice-yearly injection of Gilead’s lenacapavir achieves 100% protection in landmark HIV prevention trial
Gilead Sciences’ twice-yearly injectable lenacapavir demonstrated complete protection against HIV infection in a landmark Phase 3 trial, potentially revolutionising HIV prevention strategies for vulnerable populations.
In a remarkable advancement for HIV prevention, Gilead Sciences has announced groundbreaking results from its PURPOSE 1 trial [1], evaluating the efficacy of lenacapavir, a novel injectable HIV-1 capsid inhibitor, for pre-exposure prophylaxis (PrEP) in cisgender women. The interim analysis of this pivotal Phase 3 study revealed an unprecedented 100% efficacy in preventing HIV infection when administered twice yearly.
The PURPOSE 1 trial, conducted across 25 sites in South Africa and three in Uganda, enrolled over 5,300 cisgender women and adolescent girls aged 16-25. This demographic represents a population particularly vulnerable to HIV infection in eastern and southern Africa. The study’s primary objective was to evaluate the safety and efficacy of subcutaneous lenacapavir injections administered every six months compared to the current standard of care, daily oral Truvada (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF).
In a striking outcome, none of the 2,134 women who received lenacapavir contracted HIV during the study period, translating to an incidence rate of 0.00 per 100 person-years. This result stands in stark contrast to the 16 incident cases (1.69 per 100 person-years) observed among the 1,068 women in the Truvada group. The lenacapavir arm demonstrated statistical superiority not only over the background HIV incidence but also over once-daily Truvada (p<0.0001 for both endpoints).
Merdad Parsey, MD, PhD, Chief Medical Officer at Gilead Sciences, commented on the significance of these findings: “With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections. We look forward to additional results from the ongoing PURPOSE clinical programme and continuing toward our goal of helping to end the HIV epidemic for everyone, everywhere.”
Trial design and additional findings
The PURPOSE 1 trial employed a double-blind, randomised design with a 2:2:1 ratio for lenacapavir, Descovy (emtricitabine 200mg and tenofovir alafenamide 25mg; F/TAF), and Truvada, respectively. Notably, the study did not include a placebo arm, as withholding effective PrEP options was deemed unethical. Instead, the trial used background HIV incidence as the primary comparator and Truvada as a secondary comparator.
Interestingly, the Descovy arm showed results numerically similar to Truvada, with 39 incident cases among 2,136 women (incidence 2.02 per 100 person-years). This arm did not demonstrate statistical superiority to the background HIV incidence. Researchers noted that adherence challenges to daily oral PrEP regimens are common among cisgender women, and further analyses of adherence patterns for both Descovy and Truvada are ongoing.
Safety and tolerability
Throughout the trial, lenacapavir was generally well-tolerated, with no significant or new safety concerns identified. Similarly, both Descovy and Truvada maintained their established safety profiles, with no novel concerns arising during the study.
Implications for global HIV prevention
The results of the PURPOSE 1 trial represent a potential paradigm shift in HIV prevention strategies, particularly for populations who may struggle with daily oral PrEP regimens. Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and past President of the International AIDS Society, highlighted the significance of these findings:
“Twice-yearly lenacapavir for PrEP, if approved, could provide a critical new choice for HIV prevention that fits into the lives of many people who could benefit from PrEP around the world – especially cisgender women. While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule.”
Next steps and ongoing research
Based on these promising results, the independent Data Monitoring Committee recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants. The company plans to submit regulatory filings in the coming months, incorporating data from both PURPOSE 1 and the ongoing PURPOSE 2 trial [1].
PURPOSE 2, expected to report results in late 2024 or early 2025, is evaluating lenacapavir for PrEP in cisgender men who have sex with men, transgender men, transgender women, and gender non-binary individuals who have sex with partners assigned male at birth. This trial is being conducted across multiple countries, including Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States.
Gilead emphasises its commitment to partnering with communities disproportionately affected by HIV, ensuring that trial designs and implementation strategies are informed by community input. The company also plans to outline its access approach for high-incidence, resource-limited countries, primarily focusing on low- and lower-middle-income nations.
Conclusion
The unprecedented efficacy demonstrated by lenacapavir in the PURPOSE 1 trial marks a significant milestone in HIV prevention research. If approved, this twice-yearly injectable PrEP option could dramatically improve HIV prevention efforts, particularly among populations who face challenges with daily oral regimens. As the global community continues to work towards ending the HIV epidemic, innovations like lenacapavir offer renewed hope in achieving this goal.
Reference:
- The PURPOSE studies: https://www.purposestudies.com/
