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Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024
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- PURPOSE 1 Data Showed Zero Infections and 100% Efficacy and Superiority of Lenacapavir to Background HIV Incidence and Daily Truvada ® for PrEP -
- If Approved, Lenacapavir Would be the First and Only Twice-Yearly PrEP Choice and Could Address Critical Gaps in Uptake and Adherence for Individuals Who Need or Want PrEP -
- Gilead Commits to Prioritizing Swift Access and Enabling Efficient Paths for Regulatory Approval of Lenacapavir for PrEP in High-Incidence, Resource-Limited Countries -
Full press release here-
https://www.gilead.com/news-and-press/press-room/press-releases/2024/7/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced full efficacy and safety results from its pivotal, Phase 3 PURPOSE 1 trial. Detailed data from the trial's interim analysis announced in June showed that lenacapavir, the company's twice-yearly injectable HIV-1 capsid inhibitor, demonstrated zero infections, 100% efficacy and superiority to background HIV incidence for the investigational use of HIV prevention in cisgender women (women assigned female at birth). Lenacapavir also demonstrated superior prevention of HIV infections when compared with once-daily oral Truvada (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF).
The new data provide details on the efficacy, safety and tolerability of twice-yearly lenacapavir injections; drug adherence among trial participants, including poor levels of adherence to daily oral pre-exposure prophylaxis (PrEP) and high levels of adherence to lenacapavir; and demographic and behavioral characteristics of trial participants, including pregnant women and adolescents.
The data are being presented at a special late-breaking session at the 25th International AIDS Conference (AIDS 2024) in Munich, Germany and were published today in The New England Journal of Medicine.
"These stellar results show that twice-yearly lenacapavir for PrEP, if approved, could offer a highly effective, tolerable and discreet choice that could potentially improve PrEP uptake and persistence, helping us to reduce HIV in cisgender women globally," said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and former President of the International AIDS Society. "PURPOSE 1 also sets a new standard for person-centered HIV prevention trials, demonstrating what can happen when a thoughtful scientific and community-focused trial design, a promising drug candidate and an inclusive trial implementation plan come together."
To ensure the groundbreaking data from PURPOSE 1 translates into decreased HIV incidence globally, Gilead is building an access strategy that prioritizes speed and enables the most efficient path for the regulatory approval of twice-yearly lenacapavir for PrEP in countries that account for most of the global disease burden.
For more information, see Gilead's statement on access planning in high-incidence, resource-limited countries for lenacapavir for PrEP.
Zero infections and 100% efficacy observed for lenacapavir at interim analysis
Overall, lenacapavir was highly effective among trial participants, with zero HIV infections observed in the lenacapavir group (0/100 person-years; 95% CI, 0.00 to 0.19) compared to background HIV incidence (bHIV) (2.41/100 person-years; 95% CI, 1.82 to 3.19), translating to a 100% reduction in HIV infections. Additionally, compared to once-daily Truvada, lenacapavir reduced HIV incidence by 100%, a result that was statistically superior (IRR 0; 95% CI, p<0.0001).
Per trial protocol, because PURPOSE 1 met its key efficacy endpoints of superiority of twice-yearly lenacapavir to bHIV and once-daily oral Truvada at interim analysis, the independent Data Monitoring Committee recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants. As of July 23, more than 840 trial participants have already opted to switch to lenacapavir.
High adherence to and persistence of twice-yearly injectable lenacapavir
Adherence to lenacapavir and to placebo injections included in the oral PrEP study groups was high: 91.5% of all trial participants received on-time injections at week 26, and 92.8% of participants received on-time injections at one year. On-time injection rates (within 28 weeks of prior injection) were similar across all study groups, whether receiving lenacapavir or placebo injections.
Incident HIV infections in Descovy and Truvada trial groups
Sixteen incident HIV cases among 1,068 women were observed in the Truvada group (1.69/100 person-years; 95% CI, 0.96 to 2.74) and 39 incident HIV cases among 2,136 women were observed in the Descovy group (2.02/100 person-years; 95% CI, 1.44 to 2.76).
HIV incidence with Descovy was not different from bHIV (IRR 0.84; 95% CI, 0.55 to 1.28; p=0.21) in the primary efficacy analysis and no evidence of difference was observed compared to Truvada (IRR 1.20; 95% CI, 0.67 to 2.14) in the secondary efficacy analysis.
Poor adherence among women taking once-daily oral Descovy and Truvada
Adherence to once-daily oral Descovy and Truvada, measured through detection of tenofovir diphosphate in blood samples from a subset of patients, was low and declined over time. These adherence levels are consistent with prior reports of low adherence of daily oral PrEP among cohorts of cisgender women, especially among younger women, across geographies.
Lenacapavir and Descovy were generally well tolerated
There were no new safety concerns identified, and lenacapavir, Descovy and Truvada were generally well tolerated.
For lenacapavir and Descovy, aside from injection site reactions (ISRs), the most common adverse events (AEs) observed were headache (lenacapavir: 13.3%; Descovy: 16.5%), urinary tract infection (lenacapavir: 14.4%; Descovy 14.3%), genitourinary chlamydia infection (lenacapavir: 14.0%; Descovy 14.8%) and nausea (lenacapavir: 6.7%; Descovy: 10.9%).
Serious AEs were reported in 2.8% (n=59) of participants in the lenacapavir group, compared to 4.0% (n=85) in the Descovy group and 3.3% (n=35) in the Truvada group. Frequency of AEs was similar across study groups.
No serious injection site reactions
A total of 25,329 injections were administered: 10,154 in 2,138 participants assigned to the lenacapavir group, and 15,175 in 3,206 participants receiving placebo injections in the Descovy and Truvada groups. ISRs related to the study drug or injection procedures were the most common AEs observed (lenacapavir: 68.8%; placebo: 34.9%), and there were no serious ISRs among participants receiving lenacapavir or placebo injections.
Lenacapavir is injected into the subcutaneous layer of fat in the abdomen to form a drug depot, which will 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. About 64% (63.8%) of women in the lenacapavir group experienced nodules compared to 16.6% who received placebo injections. ISR incidence, including nodules, decreased with subsequent injections.
Four women in the lenacapavir group (0.2%) discontinued study drug due to ISRs, compared to zero women who discontinued due to ISRs on placebo.
First adult pivotal HIV prevention trial to include pregnant women and adolescents
As a result of strong community input from advocates in South Africa and Uganda, PURPOSE 1 is the first HIV prevention trial to intentionally include pregnant and lactating women. There were 510 pregnancies among 487 participants: 193 among women in the lenacapavir group, with zero HIV infections; 219 among women in the Descovy group, with four HIV infections; and 98 among women in the Truvada group, with one HIV infection. At the time of interim analysis, 54.3% of pregnancies were completed and 45.7% were ongoing. Available pregnancy outcomes were similar to those expected for the population.
Community advocates also stressed the importance of including adolescents and young people in PURPOSE 1. The median age of all trial participants was 21 years, and 124 (2.3%) participants were under 18 years.
PURPOSE 2 results expected late 2024/early 2025
Gilead expects results in late 2024/early 2025 from the program's other pivotal trial, PURPOSE 2, which is assessing twice-yearly lenacapavir for PrEP among cisgender men, transgender men, transgender women and gender non-binary individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States who have sex with partners assigned male at birth. The regulatory filing for lenacapavir for PrEP will include the results of both PURPOSE 1 and PURPOSE 2, if positive, to ensure lenacapavir for PrEP can be approved for multiple populations and communities most in need of additional HIV prevention options.
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