A Once-Yearly PrEP? Gilead’s Lenacapavir Shows Promise as Company Plots Phase 3

Overview of Lenacapavir and Current Developments

Gilead Sciences is garnering attention in the pharmaceutical sector once again with its promising candidate, lenacapavir, which aims to revolutionize HIV prevention through pre-exposure prophylaxis (PrEP). Initially demonstrating impressive results in twice-yearly dosing regimens, lenacapavir has shown potential for an even more favorable once-yearly formulation, significantly altering the landscape for HIV prevention.

During a recent small Phase 1 trial, which was presented at the Conference on Retroviruses and Opportunistic Infections and published in *The Lancet*, preliminary data showed that two different once-yearly formulations of lenacapavir achieved blood concentrations surpassing those recorded with the twice-yearly variant. Gilead plans to move forward with a Phase 3 clinical trial for this once-a-year treatment in the latter half of 2023, aiming for regulatory submissions by 2027, according to Jared Baeten, M.D., Ph.D., Gilead’s Vice President of HIV Clinical Development.

Insights into Lenacapavir’s Mechanism and Administration

Comprised as subcutaneous injections delivering 927 mg every six months, the twice-yearly lenacapavir is presently under FDA’s priority review, with a decision expected by June 19. Meanwhile, for the once-yearly regimen, Gilead explored two intramuscular formulations—both at a 5 g dose—with 5% and 10% ethanol concentrations to enhance injection comfort. The choice of intramuscular administration was made to ensure better pharmacokinetics than the subcutaneous route.

Baeten emphasized the importance of aligning dosing intervals with patient needs through discussions with the scientific community and those affected by HIV. The company’s decision to seek out longer dosing intervals reflects an increasing demand for more convenient treatment options in HIV care.

Clinical Trial Results and Efficacy

The Phase 1 trial involved 40 subjects, split evenly among the two formulations of lenacapavir. Remarkably, after 12 months, the median concentration of lenacapavir in blood observed was 57 ng/mL for one formulation and 65.5 ng/mL for the other. Notably, these levels exceeded the 23.4 ng/mL identified with the twice-yearly subcutaneous variant after 26 weeks.

Peak blood concentrations were achieved within 10 to 12 weeks, and the levels maintained stability throughout the study duration. The safety profile revealed that both formulations were well-tolerated, with no grade 4 treatment-emergent adverse events recorded. There were some grade 3 lab abnormalities, primarily related to low-density lipoprotein (LDL) cholesterol levels, which were not clearly linked to lenacapavir exposure.

Strategic Next Steps for Gilead

Moving into Phase 3, Gilead will need to address several key considerations based on the early-stage data. The notably higher Ctrough (the measurement of a drug’s blood concentration just before the next dose) indicates that the optimal clinical dose could likely be lower than the current 5 g formulation. Gilead will utilize existing pharmacology data to refine dosing for the upcoming trials, avoiding the launch of an additional study.

Additionally, the format of the dosing—whether to incorporate an oral loading dose—remains under consideration. Past studies using oral lenacapavir at initial dosing helped achieve desired plasma concentration levels, a strategy that may also be necessary for the intramuscular formulations to ensure effective dosing speed.

Lastly, as a reward for innovation, Gilead’s upcoming Phase 3 program may explore a pharmacological endpoint rather than the more traditional hard efficacy endpoint of infection rates observed previously.

Market Implications and Future Opportunities

The commercialization of lenacapavir not only stands to bolster Gilead’s position in the HIV prevention market but could reshape treatment landscapes by providing more patient-friendly dosing options. As the company progresses with its trials and prepares for potential regulatory filings, it can be expected that the competitive dynamics in the HIV prevention sector may shift significantly.

Currently, Gilead’s twice-yearly lenacapavir is poised for potential dominance in the market, yet with the advent of once-yearly dosing, the attractiveness of this innovative solution could lead to expanded accessibility and adherence, ultimately resulting in improved public health outcomes.

For investors keen on biotech opportunities, Gilead Sciences is certainly one to watch as the company aims to deliver on its promise of a groundbreaking PrEP solution that meets the evolving needs of patients.

With critical developments on the horizon for lenacapavir, stakeholders should remain vigilant as new data emerges and markets react.

Conclusion

Given the promising results from the Phase 1 study of lenacapavir in a once-yearly formulation, Gilead Sciences appears well-positioned to innovate in the HIV prevention arena. Through strategic clinical exploration and patient-centric dosage options, the company could secure a significant market share that meets both clinical needs and investor expectations. The coming months will prove pivotal for gauging the drug’s FDA trajectory and its broader implications in the pharmaceutical landscape.