A recent Phase 3 clinical trial (NCT04994509), dubbed "PURPOSE 1," has yielded promising results for a new HIV/AIDS prevention drug, potentially revolutionizing the field of HIV prophylaxis. The study, conducted by Gilead Sciences, evaluated the safety and efficacy of Lenacapavir, a novel long-acting HIV capsid inhibitor, in preventing HIV infection.

src. Gilead Science

Study Design and Results

The double-blind, randomized trial involved over 5,300 women aged 6 to 25 years across 25 sites in South Africa and 3 sites in Uganda. Participants were randomly assigned in a 2:2:1 ratio to receive:

1. Lenacapavir injection every six months

2. Daily oral Descovy (emtricitabine 200mg and tenofovir alafenamide 25mg)

3. Daily oral Truvada

Both Descovy and Truvada, also developed by Gilead, are established pre-exposure prophylaxis (PrEP) medications used as control groups in this study.

The results were striking:

• Lenacapavir group (2,134 women): 0 HIV infections

• Truvada group (1,068 women): 16 HIV infections (1.69 cases per 100 person-years)

• Descovy group (2,136 women): 39 HIV infections (2.02 cases per 100 person-years)

Lenacapavir demonstrated excellent tolerability with no major or new safety concerns. Similarly, Descovy and Truvada were well-tolerated with no new safety issues identified.

Implications and Future Prospects

The 100% efficacy rate of Lenacapavir represents a significant breakthrough in HIV prevention. If approved, it could offer a convenient alternative to daily oral medications, potentially improving adherence and reducing stigma associated with daily PrEP regimens.

Dr. Merdad Parsey, Gilead's Global Chief Medical Officer, emphasized the drug's potential as a crucial new tool in HIV prevention. The company anticipates results from another pivotal trial evaluating Lenacapavir's efficacy in individuals of various sexual orientations by late 2024 or early 2025. If these results are positive, Lenacapavir could be marketed for HIV prevention as early as the end of 2025.

Mechanism of Action

Lenacapavir is a first-in-class, long-acting HIV capsid inhibitor. It interferes with the assembly and disassembly of the HIV virus capsid protein, acting at multiple stages of the HIV-1 lifecycle. Previous trials have shown that Lenacapavir maintains its efficacy with injections every six months. (Read more on Lenacapavir's mechanism of action)

Advantages over Current PrEP Options

While current oral PrEP medications like Truvada and Descovy are highly effective when used correctly, adherence has been a challenge for some individuals due to daily dosing requirements and potential stigma. Lenacapavir's biannual dosing schedule could significantly improve adherence and reduce stigma-related barriers to PrEP use.

Additionally, as a novel drug targeting a new site of action, Lenacapavir may have advantages in terms of drug resistance compared to older medications that have been in clinical use for longer periods.

Regulatory Status

Lenacapavir received FDA approval in December 2022 for use in combination with other antiretroviral drugs to treat multi-drug resistant HIV infections in adults. However, its use as a PrEP medication represents a new indication that will require separate regulatory approval before market entry.

Unibest Offering

The development of Lenacapavir as a highly effective, long-acting HIV prevention drug marks a significant advancement in the fight against HIV/AIDS. If approved for PrEP, it could provide a valuable new option for HIV prevention, particularly benefiting populations who face challenges with daily oral medication regimens. At Unibest, we stand with the global community to continue to work towards ending the HIV epidemic. We offer the following Lenacapavir intermediates to help develop API:

- CAS No. 1620056-47-4

- CAS No. 2109226-54-0

- CAS No. 2189684-54-4, which is synthesized from CAS No. 1620056-47-4 and CAS No. 2109226-54-0

- CAS No. 2189684-53-3

- CAS No. 2375019-85-3

- CAS No. 1620056-83-8