Gilead's Lenacapavir Shows Promise as Once-Yearly HIV Prevention Option

Gilead Sciences has made significant strides in the development of lenacapavir, a long-acting HIV prevention drug, with new data suggesting the potential for once-yearly dosing. This advancement could revolutionize pre-exposure prophylaxis (PrEP) strategies and improve adherence for individuals at risk of HIV infection.

Phase 1 Results Exceed Expectations

Recent phase 1 trial results, presented at the Conference on Retroviruses and Opportunistic Infections and published in The Lancet, have demonstrated that two different once-yearly formulations of lenacapavir achieved blood concentrations surpassing those associated with the efficacy of twice-yearly dosing in phase 3 PrEP studies.

The small-scale study examined two intramuscular presentations of lenacapavir, both administered in a 5-g dose. One formulation contained 5% ethanol, while the other contained 10%, aimed at reducing the thickness of the injection. At the one-year mark, median concentrations of lenacapavir in the blood were 57 ng/mL and 65.5 ng/mL for the respective formulations, significantly exceeding the 23.4 ng/mL recorded for twice-yearly subcutaneous lenacapavir at 26 weeks in previous phase 3 trials.

Dr. Jared Baeten, Gilead's vice president of HIV clinical development, emphasized the importance of these findings: "We've talked with the scientific community and with people affected by HIV about where the unmet need is, and people said 'longer' [dosing intervals]."

Safety Profile and Next Steps

Both formulations were well-tolerated, with no grade 4 treatment-emergent adverse events reported. The most common grade 3 adverse event was elevated low-density lipoprotein (LDL) cholesterol levels, occurring in four individuals across both formulations. However, these cases were not directly linked to lenacapavir exposure.

Injection-site pain was common but generally mild and was substantially reduced by pretreatment with ice at the injection sites. The positive results from this phase 1 trial have paved the way for Gilead to initiate a phase 3 program for once-yearly lenacapavir in the second half of 2023, with potential regulatory filings anticipated in 2027.

Implications for HIV Prevention

As Gilead prepares for the next phase of development, several key considerations have emerged. The higher-than-expected blood concentration levels suggest that the optimal clinical dose for future development may be lower than the 5g used in the phase 1 trial. Additionally, the company is evaluating whether an oral loading dose may be necessary to achieve desired blood concentration levels more rapidly.

While the twice-yearly formulation of lenacapavir is currently under FDA priority review for use as a PrEP option, with a decision expected by June 19, 2023, the prospect of a once-yearly option could significantly impact HIV prevention strategies. Lenacapavir is already approved under the brand name Sunlenca for use in combination with other antiretrovirals to treat multidrug-resistant HIV infection.

The development of a once-yearly PrEP option has the potential to address adherence challenges and reduce the burden of frequent dosing, potentially improving overall effectiveness in HIV prevention efforts. As the pharmaceutical industry continues to innovate in long-acting HIV prevention methods, lenacapavir's progress represents a significant step forward in the ongoing fight against HIV/AIDS.