The US Food and Drug Administration (FDA) has granted tentative approval to Dr. Reddy's Laboratories' generic lenacapavir injection for HIV pre-exposure prophylaxis (PrEP), potentially expanding access to HIV prevention across 120 low- and middle-income countries. The decision was announced on November 2 by the Clinton Health Access Initiative (CHAI) and its partners.
The twice-yearly injection is intended to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg. Dr. Reddy's developed the generic with financial, technical, and regulatory support from CHAI, Unitaid, and Wits RHI.
Under the FDA's international HIV drug review program, tentative approval does not authorize US marketing while applicable patent protections remain in effect. Gilead Sciences' branded formulation, lenacapavir (Yeztugo), remains patent-protected in the US. However, CHAI noted the decision can help accelerate national regulatory reviews in participating countries.
CHAI reported that the injectable formulation will cost $40 per person annually under the partnership agreement. Unitaid separately stated that the required initial oral loading course is priced at up to $17.
Dr. Reddy's combined lenacapavir's HIV treatment and prevention indications in a single application under the FDA's 505(b)(2) pathway, CHAI reported. This pathway allows applicants to rely partly on existing safety and efficacy evidence rather than conducting all clinical trials independently.
According to the FDA-approved prescribing information for previously approved lenacapavir, the drug is a capsid inhibitor that interferes with multiple stages of HIV replication. Its preventive efficacy was evaluated in the phase 3 PURPOSE 1 and PURPOSE 2 trials, published in The New England Journal of Medicine. Both evaluated twice-yearly subcutaneous lenacapavir against estimated background HIV incidence and daily oral PrEP.
In PURPOSE 1, a randomized trial involving adolescent girls and young women in South Africa and Uganda, no HIV infections occurred among 2,134 participants receiving lenacapavir, compared with 16 among 1,068 receiving daily emtricitabine/tenofovir disoproxil fumarate.
In PURPOSE 2, involving cisgender men, transgender participants, and gender-nonbinary individuals, HIV infections occurred in 2 of 2,179 participants receiving lenacapavir and 9 of 1,086 receiving the oral comparator. Lenacapavir reduced HIV incidence by 96% relative to estimated background incidence and by 89% compared with daily oral PrEP.
These findings concern Gilead's original formulation rather than a separate efficacy trial of Dr. Reddy's generic.
The prescribing information carries a boxed warning about drug resistance when lenacapavir is used in individuals with undiagnosed HIV-1 infection. The label requires HIV testing before treatment initiation and before each subsequent injection. Common adverse reactions noted include injection-site reactions, headache, and nausea.
CHAI noted that initial supplies are expected before the end of the year, with broader availability anticipated in 2027, although procurement, funding, and distribution arrangements will affect access.
Sources: Clinton Health Access Initiative, Unitaid,NEJM (PURPOSE 1), NEJM(PURPOSE 2), DailyMed, FDA PEPFAR FAQs,FDA PDUFA V Fee Information
