Developing a vaccine for HIV prevention is fraught with challenges, but drugs for prevention are evolving through iterations.

On June 20th, Gilead Sciences announced that the top-line results from the interim analysis of the critical Phase 3 PURPOSE 1 clinical trial showed that the HIV-1 capsid inhibitor lenacapavir, administered twice a year as an injection, demonstrated 100% efficacy in HIV prevention studies targeting cisgender women.

Gilead stated that this is the first Phase 3 clinical trial for HIV prevention to show zero infections.

The PURPOSE 1 is a Phase 3, double-blind, randomized study assessing the safety and efficacy of lenacapavir administered subcutaneously twice a year and daily oral doses of Descovy (emtricitabine 200mg/tenofovir alafenamide 25mg, F/TAF) for pre-exposure prophylaxis (PrEP). The study includes over 5,300 cisgender women and adolescent girls aged 16-25 from 25 locations in South Africa and 3 locations in Uganda. The drugs are tested in parallel, with one group receiving lenacapavir administered twice a year and another group taking daily oral doses of Descovy. Additionally, a third group takes daily oral doses of Truvada (emtricitabine 200mg/tenofovir disoproxil fumarate 300mg). Participants are randomly assigned to the lenacapavir, Descovy, and Truvada groups in a 2:2:1 ratio.

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Among the 2,134 women in the lenacapavir group, there was not a single case of HIV infection (incidence rate of 0.00 per 100 person-years).

Gilead stated that the PURPOSE 1 trial met its key efficacy endpoint, showing the superiority of lenacapavir administered twice a year compared to daily oral Truvada and the background incidence rate of HIV. Based on these results, the independent Data Monitoring Committee recommended that Gilead unblind the clinical trial and provide open-label lenacapavir to all participants.

Gilead is a globally recognized enterprise in the development of antiviral drugs. In the field of pre-exposure prophylaxis for HIV, the company has launched two drugs globally, one is Truvada and the other is Descovy, both of which are also available in China. However, these drugs cannot achieve 100% efficacy in preventing HIV and are also short-acting drugs.

As a long-acting HIV drug, lenacapavir injection and tablets have been approved for marketing in the EU and the US, but the approved indication is for treatment, that is, in combination with other antiretroviral drugs, for the treatment of adult HIV-infected individuals who have received multiple treatment regimens and are multidrug-resistant. Lenacapavir has not yet been approved for marketing in China.

AIDS is one of the major public health issues faced globally, with approximately 39 million people living with HIV. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a goal and commitment to achieve 95% of people at risk of HIV infection receiving effective, comprehensive prevention measures by 2025. Therefore, preventing new HIV infections has become key to controlling the spread of AIDS. Sexual transmission is the main route of HIV transmission, including unsafe same-sex, opposite-sex, and bisexual contacts. Pre-exposure prophylaxis is an effective biological prevention method for preventing HIV infection through the use of antiviral drugs.

"Lenacapavir for pre-exposure prophylaxis administered twice a year, if approved, could provide a crucial new option for preventing HIV infection for many people around the world who can benefit from pre-exposure prophylaxis—especially cisgender women," said Dr. Linda-Gail Bekker, Director of the Desmond Tutu HIV Center at the University of Cape Town, former President of the International AIDS Society. "Although we know that traditional HIV prevention drugs are very effective when taken as prescribed, lenacapavir for pre-exposure prophylaxis administered twice a year can help address the stigmatization and discrimination issues some people may face when taking or storing oral pre-exposure prophylaxis drugs. Additionally, administration twice a year may help improve adherence and continuity of pre-exposure prophylaxis."Gilead Sciences' Chief Medical Officer, Merdad Parsey, stated that the zero infections and 100% efficacy demonstrate the potential of lenacapavir, administered twice a year, to become a new and significant option for preventing HIV infection. The company looks forward to receiving more results from the ongoing PURPOSE clinical trial and continues to move towards the goal of helping to end the global HIV epidemic.

The current efficacy data is limited to the cisgender female population. First Financial Daily reporters learned from Gilead that the submission for marketing authorization of lenacapavir for pre-exposure prophylaxis (PrEP) is pending the results of another clinical trial.

According to the information provided, Gilead expects to receive results from another key trial of the PURPOSE project, known as PURPOSE 2, by the end of 2024 or early 2025. This trial assesses the efficacy of lenacapavir administered twice a year as pre-exposure prophylaxis in cisgender men who have sex with men, as well as transgender men, transgender women, and non-binary individuals who have sexual relations with those assigned male at birth. The trial is being conducted in locations including Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. If the trial results are positive, the registration application for lenacapavir for pre-exposure prophylaxis will include the results from both PURPOSE 1 and PURPOSE 2, ensuring that lenacapavir can be approved for pre-exposure prophylaxis in multiple groups and communities that need additional HIV prevention options.