EMA: New injection for easier prevention of HIV infection in the EU and worldwide

EMA has recommended granting a marketing authorisation in the European Union (EU) for Yeytuo (lenacapavir) for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to reduce the risk of sexually acquired human immunodeficiency virus type 1 (HIV-1) infection in adults and adolescents at high risk of becoming infected. Yeytuo will facilitate PrEP uptake and compliance because it only has to be administered twice a year via a subcutaneous injection.

Yeytuo was evaluated by the CHMP, EMA’s human medicine committee, under an accelerated timetable because it is considered to be of major public health interest in the EU and the rest of the world. The CHMP simultaneously reviewed the medicine for the EU market, under the centralised procedure, and for non-EU countries, under the ‘EU-Medicines for all’ (EU-M4all) programme. This aims to make medicines that address unmet medical needs or are of major public health interest available in Europe and globally faster, while avoiding duplication of efforts from regulators. Experts from the World Health Organization (WHO), Uganda, Zambia, Kenya, Nigeria, Zimbabwe, South Africa, Thailand and Vietnam participated in the assessment.

HIV-1 infection is of major public health significance. According to the WHO, in 2024 an estimated 1.3 million people became newly infected with HIV globally, including 160,000 new HIV infections in the European region and 650,000 in Africa, the region most affected by HIV.

HIV-1 impacts the body’s immune system, particularly white blood cells that are important in helping to fight infections. If left untreated, HIV-1 infection can progress to acquired immune deficiency syndrome (AIDS), where the immune system is severely damaged, making the body vulnerable to opportunistic infections and some cancer types. The virus can be transmitted through specific body fluids, including blood, blood products, semen, vaginal fluids, rectal fluids and breast milk. Sexual intercourse is the most common mode of transmission of HIV-1.

PrEP is a cornerstone of HIV-control efforts in Europe and worldwide and is very effective at preventing infections if taken as prescribed. However, uptake and adherence are often suboptimal because access to some medicines is limited, and other available medicines require strict daily intake. This means that many people at risk in the EU and globally remain underserved by existing PrEP options, highlighting an urgent need to develop additional PrEP modalities.

Yeytuo contains lenacapavir, a first-in-class substance that binds to the proteins that make up the outer layer of HIV-1 (the capsid). By binding to these proteins, lenacapavir interferes with multiple steps in the HIV-1 lifecycle, thereby inhibiting viral replication, ultimately preventing HIV-1 infection. Of note, two tablets of Yeytuo on the first two days are required when starting the treatment, after which the medicine is given by injection every six months.

CHMP’s recommendation is based on the results of two randomised, double-blind, active-controlled, multinational trials. In the PURPOSE 1 trial, cisgender women, including pregnant and lactating women, between the age of 16 and 24 who have sex with cisgender males, were randomised in a 2:1 ratio to receive Yeytuo (n=2134) or Truvada (n=1068). At the time of the primary analysis, no new HIV-1 infections were observed in the Yeytuo group compared to 16 in the Truvada group.

In the PURPOSE 2 trial, men and gender-diverse persons from 16 years old who have sex with male partners, were randomised in a 2:1 ratio to receive Yeytuo (n=2179) or Truvada (n=1086). At the time of the primary analysis, two new HIV-1 infections were observed in the Yeytuo group compared to nine in the Truvada group. In both studies, participants who received Yeytuo showed higher adherence to their treatment than participants who received Truvada.

The most common side effects observed were injection-site reactions, including pain and hard lumps (injection site nodules) that can persist for a long time or not disappear.

Medicines submitted under the EU-M4all programme are assessed by the CHMP in collaboration with the WHO and the target countries, combining EMA’s scientific review capabilities with the expertise in epidemiology and local circumstances of WHO, experts and national regulators in the target countries. The CHMP scientific opinion under the EU-M4all procedure supports global regulatory capacity building and contributes to the protection and promotion of public health beyond the EU, by assessing medicines for countries where regulatory capacity may be limited. National regulators can rely on the CHMP‘s scientific assessment to decide on the use of the medicine in their countries.

1. The applicant for Yeytuo is Gilead Sciences Ireland Unlimited Company.
2. Yeytuo is the second medicine simultaneously reviewed by the CHMP for the EU market, under the centralised procedure, and non-EU countries, under the ‘EU-Medicines for all’ programme – or EU-M4all, and the eighteenth medicine receiving an EMA recommendation under EU-M4all.
3. The medicine has been reviewed under the trade name Yeytuo for the EU and is referred to as Lenacapavir Gilead in the context of the EU-M4all procedure.
4. Yeytuo is a duplicate marketing authorisation application of Sunlenca, a centrally authorised medicine used in combination with other antiretroviral(s) for the treatment of adults with multidrug resistant HIV-1 infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen. Sunlenca is available as tablets and subcutaneous injections.
5. The WHO published guidelines on the use of lenacapavir on 14 July: Guidelines on lenacapavir for HIV prevention and testing strategies for long-acting injectable pre-exposure prophylaxis

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SEE ALSO:

• Gilead receives positive CHMP opinions under accelerated review from European Medicines Agency for twice-yearly lenacapavir for HIV prevention
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