HIV continues to be a serious public health problem throughout the world, as some countries have seen an increase in infections when transmission had previously decreased. The World Health Organization (WHO) estimates that at the end of 2022 around 39 million people were living with HIV, two-thirds of whom (25.6 million) are in the WHO African Region.
Finding new therapies that prevent infection would help eradicate the virus. Now, the results of a clinical trial involving thousands of women in Africa show the unprecedented effectiveness of the drug lenacapavir in combating HIV. Lenacapavir is the new pre-exposure prophylaxis (PrEP) developed by Gilead and administered by injection twice a year. A clinical trial comparing it to the daily oral medication Truvada has shown it to be 100% effective with zero cases of HIV infection among women who participated in the study.
“With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections,” said Dr. Merdad Parsey, Chief Medical Officer, Gilead Sciences. “We look forward to additional results from the ongoing PURPOSE clinical program and continuing our goal of helping to end the HIV epidemic for everyone, everywhere.”
Promising results of new drug that prevents HIV
PURPOSE 1 met its key efficacy endpoints, showing superiority of lenacapavir administered twice yearly compared to Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; F/TDF) administered daily and baseline HIV incidence ( bHIV). Based on these results, the Independent Data Monitoring Committee (DMC) recommended that Gilead end the blinded phase of the trial and offer open-label lenacapavir to all participants.
PURPOSE 1, a randomized, double-blind Phase 3 study, is evaluating the safety and efficacy of subcutaneous lenacapavir administered twice yearly for pre-exposure prophylaxis (PrEP) and daily oral Descovy® (emtricitabine 200 mg and tenofovir alafenamide 25 mg; F/TAF) in more than 5,300 cisgender women and adolescents aged 16 to 25 years in 25 locations in South Africa and three in Uganda.
The drugs are being tested in parallel, with one group receiving lenacapavir twice a year and another group taking Descovy daily. Additionally, a third group was assigned to daily oral Truvada. Study participants were randomized 2:2:1 to lenacapavir, Descovy, and Truvada, respectively. Since effective PrEP options already exist, there is a general consensus in the PrEP field that a placebo group would be unethical; therefore, the trial used bHIV as the primary comparator and Truvada as the secondary comparator.
“Lenacapavir could provide a fundamental new option for HIV prevention that fits the lives of many people who could benefit from PrEP around the world”
There were no incident cases of HIV infection among the 2,134 women in the lenacapavir group (incidence 0.00 per 100 person-years). There were 16 incident cases among the 1,068 women in the Truvada group (incidence 1.69 per 100 person-years). Results demonstrated the superiority of twice-yearly lenacapavir over bHIV (primary endpoint, incidence 2.41 per 100 person-years) and the superiority of twice-yearly lenacapavir over daily Truvada. In the trial, lenacapavir was generally well tolerated and no significant or new safety concerns were identified.
The incidence of HIV in the Descovy group was numerically similar (39 incident cases among 2,136 women, incidence 2.02 per 100 person-years) to that of the Truvada group and was not statistically superior to bHIV. Previous clinical trials among cisgender women have frequently found treatment adherence problems with daily oral PrEP pills, and adherence analyzes for PURPOSE 1’s Descovy and Truvada are ongoing. In the trial, both Descovy and Truvada were generally well tolerated and no new safety concerns were identified.
“Lenacapavir given twice a year for PrEP, if approved, could provide a critical new option for HIV prevention that fits the lives of many people who could benefit from PrEP around the world, especially cisgender women.” said Linda-Gail Bekker, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and former President of the International AIDS Society.
“While we know that traditional HIV prevention options are very effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination that some people may face when taking or stockpiling oral HIV pills. PrEP, in addition to potentially helping to increase PrEP adherence and persistence given its twice-yearly dosing schedule,” he adds.
The use of lenacapavir and the use of Descovy for HIV prevention in cisgender women are experimental and have not been determined to be safe or effective and are not approved anywhere in the world. Additional PURPOSE trials evaluating lenacapavir twice a year for PrEP are ongoing, as is a second trial to test its effectiveness in men who have sex with men, as well as in transgender women and men. Results from the trial could be available in late 2024, and if positive, Gilead hopes to apply for regulatory approval for preventive lenacapavir in the United States and other countries.
Source: Gilead
