Gilead announced that its twice-yearly injectable HIV capsid inhibitor, lenacapavir, was found to be safe and tolerable for participants in a PrEP study.1
Findings from the ongoing PURPOSE 2 trial demonstrated no significant or new safety concerns identified, and lenacapavir was generally well-tolerated. Aside from injection site reactions (ISRs), the most common adverse events (AEs) observed were rectal chlamydia infection (lenacapavir: 13.2%; emtricitabine and tenofovir disoproxil (Truvada): 11.8%), oropharyngeal gonococcal infection (lenacapavir: 13.0%; Truvada: 10.9%) and rectal gonococcal infection (lenacapavir: 10.7%; Truvada: 9.1%).1
In an interview with Contagion, Jared Baeten, MD, PhD, is the senior vice president of clinical development and virology discusses how lenacapavir could influence HIV prevention guidelines and improve accessibility, particularly for those who prefer infrequent dosing.
"For HIV prevention, we need options that can fit really well into people's lives and will operate across all of that multifaceted diversity, because new HIV infections are occurring around the world in many different contexts. The Purpose results are the basis of multiple regulatory filings all around the world. We’re working to kick off those filings by the end of this year and beyond," Baeten said.
What You Need to Know
Gilead's twice-yearly injectable capsid inhibitor, lenacapavir, was found to be safe and generally well-tolerated in the ongoing Phase 3 PURPOSE 2 trial for HIV prevention.
Lenacapavir demonstrated a 99.9% prevention rate among participants in the PURPOSE 2 trial.
Gilead has signed licensing agreements with six pharmaceutical companies to manufacture and supply affordable versions of lenacapavir for 120 low- and middle-income countries, aiming to broaden global access to this prevention method if approved. Regulatory filings are expected by the end of 2024.
Study Specifics
PURPOSE 2 is a phase 3, double-blind, multicenter, randomized study evaluating the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP vs bHIV and once-daily oral Truvada in 3,273 cisgender gay, bisexual, and other men, transgender women, transgender men, and gender nonbinary individuals aged 16 years or older who have sex with partners assigned male at birth. The trial spanned 88 sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States and participants were randomized in a 2:1 ratio to lenacapavir and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and Truvada as a secondary comparator.1
Serious AEs were reported in 3.3% of participants in the lenacapavir group, compared to 4.0% in the Truvada group. Frequency of AEs was consistent between study groups.1
“These data reinforce that twice-yearly lenacapavir could be a highly effective and potentially game-changing HIV prevention choice that we have long hoped for in our efforts to end the HIV epidemic,” said Colleen Kelley, MD, MPH, Professor of Medicine at Emory University and a PURPOSE 2 Principal Investigator. “PURPOSE 2 was intentionally designed to reflect the lives and locations of many people who are disproportionately affected by HIV around the world by focusing on gender, racial, ethnic and geographic diversity.”1
Lenacapavir is injected into the subcutaneous layer of fat in the abdomen to form a drug depot, which should get smaller and resolve, or reduce in size substantially, prior to the next lenacapavir injection. The drug depot may be palpable as a bump or nodule but is usually not visible. A total of 15,239 lenacapavir and placebo injections were administered during the trial. The most commonly reported ISRs were subcutaneous nodules (lenacapavir: 63.4%; placebo: 39.2%), injection site pain (lenacapavir: 56.4%; placebo: 53.4%) and erythema (lenacapavir: 17.3%; placebo: 19.4%). Twenty-nine people (<1%) across both groups discontinued due to ISRs. ISR incidence, including nodules, decreased with subsequent injections.1
Efficacy
The company announced last month that lenacapavir was more efficacious in preventing HIV infection than a daily PrEP pill, emtricitabine and tenofovir disoproxil.2
Early data was shared from the PURPOSE 2 phase 3 clinical trial. The investigators reported there were 2 confirmed cases of HIV among 2,180 participants in the lenacapavir group (incidence 0.10 per 100 person-years); thus demonstrating a 99.9% prevention rate amongst participants. The results demonstrated superiority of twice-yearly lenacapavir over bHIV (incidence 2.37 per 100 person-years), with 96% relative risk reduction (incidence rate ratio 0.04, p<0.0001). 2
There were 9 incident cases among 1,087 individuals in the Truvada group (incidence 0.93 per 100 person-years). Twice-yearly lenacapavir was 89% more effective than once-daily emtricitabine and tenofovir disoproxil (incidence rate ratio 0.11, p=0.00245).2
Lenacapavir’s Access to Low and Middle Income Countries
Last week, Gilead announced that it had signed non-exclusive, royalty-free voluntary licensing agreements with 6 pharmaceutical companies to manufacture and supply high-quality, low-cost versions of lenacapavir for 120 primarily low and middle income countries, and is working on a strategy for broad, global access to lenacapavir for PrEP, if approved.3
Regulatory Filing
Based on the data from this trial and the Purpose 1 study, the company said it also plans to begin filing for regulatory approvals this year.
"Filings may have to involve approvals in the hands of regulators who are excited to interface on those approvals. If they happen, they are just one step toward what needs to occur, which is accessibility and equitable accessibility for people all around the world. Because we at Gilead, I think we share this with stakeholders and colleagues everywhere, would like nothing more than to end new infections for HIV, to end this epidemic everywhere, for everyone."
