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

Gilead Sciences has captured significant attention in the healthcare sector with its latest advancements in HIV prevention. The company’s investigational drug, lenacapavir, has shown remarkable potential as a once-yearly preexposure prophylaxis (PrEP) treatment option for HIV, following impressive clinical results for its twice-yearly counterpart.

Advancements in Clinical Trials

Recently, two formulations of lenacapavir designed for administration once a year displayed blood concentrations exceeding the efficacy needs established by twice-yearly lenacapavir. These promising pharmacokinetic results stemmed from a small phase 1 trial, which was presented at the Conference on Retroviruses and Opportunistic Infections and simultaneously published in The Lancet.

Gilead’s plans for the future of lenacapavir are ambitious. According to Jared Baeten, M.D., Ph.D., Gilead’s vice president of HIV clinical development, the company is gearing up to launch a phase 3 program for the once-yearly formulation within the second half of the year, with regulatory filings expected by 2027.

Current Status of Lenacapavir

Currently, Gilead’s application for lenacapavir as a twice-yearly PrEP option is under priority review by the FDA, with an anticipated decision by June 19. The drug has already received approval as Sunlenca for treating multidrug-resistant HIV infection.

Here’s how the twice-yearly formulation works: administered via subcutaneous injection of 927 mg every six months, it has set a strong precedent for effectiveness. Now, the focus shifts to the once-yearly administration, which researchers investigated by using two intramuscular presentations of lenacapavir, each at a 5g dose. These formulations were created with varying percentages of ethanol to lower injection thickness.

Research Findings and Implications

The phase 1 trial involved 20 participants per formulation, and results indicated that at the one-year mark, the median concentrations of lenacapavir in the blood were 57 ng/mL and 65.5 ng/mL. Notably, both figures surpassed the concentration of 23.4 ng/mL previously seen with the twice-yearly formulation at the end of 26 weeks from the phase 3 Purpose studies.

Peak concentrations for the intramuscular formulations were reached after a median of approximately 12 weeks, with drug levels remaining consistent and significantly above the twice-yearly subcutaneous treatment throughout the remaining study period. Participants’ overall blood concentration levels at 12 months were consistent with or exceeded those seen at the half-year mark for the subcutaneous option, demonstrating a strong profile for the once-yearly option.

Safety and Tolerability

In terms of safety, both formulations were well tolerated among participants, with no grade 4 treatment-emergent adverse events reported. Though some grade 3 lab abnormalities were noted, they appeared unlikely to be directly linked to lenacapavir. The primary grade 3 event was an elevated low-density lipoprotein (LDL) cholesterol level, which occurred in four subjects, all of whom exhibited abnormal LDL levels before the trial. Mild injection-site pain was reported, though it was significantly reduced with ice treatment prior to injection.

Path Forward for Lenacapavir

The positive results from the phase 1 trial provide Gilead with critical insights as they design their phase 3 program. One of the key considerations involves the optimal clinical dosing. Given that the intramuscular formulation’s Ctrough — or the measurement of blood concentration before the next dose — was notably higher than anticipated, Gilead researchers indicated a lower dose may be necessary for future studies.

Additionally, the need for an initial oral loading dose to increase plasma concentrations quickly still requires assessment. There remains an ongoing conversation regarding whether the new intracmuscular formulation might benefit from similar loadings as seen with the subcutaneous versions.

Conclusion

As Gilead navigates the complexities of launching a once-yearly lenacapavir formulation, the company remains focused on establishing a robust and effective PrEP option for those at risk of HIV infection. If successful, this drug could transform the landscape of HIV prevention, providing new avenues for individuals seeking longer dosing intervals and enhanced convenience in their healthcare journeys.

The progress of lenacapavir not only illustrates advancements in pharmacological science but also signals Gilead’s commitment to addressing the urgent unmet needs of the HIV community.