Merck Launches Phase 3 Trials for Monthly Oral HIV PrEP, Challenging Gilead's Dominance

Merck & Co. is making a bold move in the HIV prevention landscape with the initiation of two phase 3 trials for its once-monthly oral pre-exposure prophylaxis (PrEP) candidate, MK-8527. This development comes as Gilead Sciences' twice-yearly injectable PrEP, Yeztugo (lenacapavir), has recently gained approval and market dominance.

Merck's Strategic Push into HIV Prevention

The New Jersey-based pharmaceutical giant has partnered with the Gates Foundation to launch the EXPrESSIVE-10 and EXPrESSIVE-11 trials. These studies aim to enroll approximately 4,400 participants across multiple countries, primarily focusing on regions with high HIV prevalence.

EXPrESSIVE-10 will commence enrollment of women and girls at 31 sites across Kenya, South Africa, and Uganda in the coming months. Meanwhile, EXPrESSIVE-11 is set to begin in August, recruiting sexually active individuals from 16 countries.

Both trials will compare the efficacy of MK-8527 in reducing HIV incidence against Gilead's daily oral PrEP pill, Truvada (emtricitabine/tenofovir). This head-to-head comparison underscores Merck's confidence in its candidate and its potential to reshape the PrEP market.

Technical Insights and Market Implications

MK-8527 operates by inhibiting the reverse transcriptase enzyme crucial for HIV replication. Merck recently concluded a phase 2 trial of the asset, reporting comparable adverse event rates between the treatment and placebo arms. The company plans to present more comprehensive data from this study at the upcoming AIDS Society Conference on HIV Science in Rwanda on July 16.

While Gilead's Yeztugo has been hailed as a scientific breakthrough with projected peak sales of $8 billion annually, Merck is betting on a significant market segment that may prefer oral medication over injections. This strategy could potentially address the current gap in global PrEP coverage, which stands at only 18% of the estimated need.

Collaborative Efforts and Industry Impact

The Gates Foundation's involvement extends beyond financial support. The nonprofit is providing grant funding to the International Clinical Research Center (ICRC) at the University of Washington and the University of Alabama at Birmingham to support EXPrESSIVE-10. This funding will facilitate community advisory groups, patient recruitment, and retention efforts.

Trevor Mundel, Ph.D., president of global health at the Gates Foundation, emphasized the urgent need for more PrEP options, stating, "These phase 3 trials are a key step toward translating progress into longer-acting options that could help turn the tide on HIV."

This development coincides with the World Health Organization's recent update to its HIV prevention guidelines, which now recommend Yeztugo. The timing of Merck's trials suggests an intensifying competition in the HIV prevention space, potentially leading to more diverse and accessible options for at-risk populations worldwide.