Gilead’s Investigational Lenacapavir Demonstrates Sustained Long-Acting Efficacy Through Week 26 in Data Presented at CROI
– Lenacapavir Maintained High Rates of Virologic Suppression Among Heavily Treatment-Experienced People with Multi-Drug Resistant HIV –
– Late-Breaking Preclinical Data Support Further Study of Lenacapavir as a Long-Acting Agent for HIV Prevention –
“Some heavily treatment-experienced people with multi-drug resistant HIV are unable to maintain viral suppression with currently available treatment regimens. The CAPELLA trial enrolled people who were failing their regimens with a detectable viral load and had very few remaining options due to multi-drug resistance, which presents a formidable barrier to treatment,” noted
Lenacapavir is being developed as the foundation of a long-acting regimen in combination with other antiretroviral agents for the treatment of HIV-1 infection. Lenacapavir is a potential first-in-class capsid inhibitor that is designed to inhibit HIV replication as it interferes with the disassembly of the HIV capsid core, inhibits the role of capsid proteins during viral RNA/DNA translocation to the nucleus, and disrupts assembly of the capsid core. If approved, lenacapavir would be the first HIV capsid inhibitor available for the treatment of HIV-1 infection. In
“Significant advances in antiretroviral therapy have enabled many people living with HIV to achieve viral suppression if adherent to their medications. However, in my practice I still see some people struggle with adherence to a complex regimen, which may lead to difficulty maintaining viral suppression and eventual drug resistance,” said
In addition to the new interim findings from the CAPELLA trial, Gilead also presented the results of a preclinical non-human primate study with GS-CA1, a close lenacapavir analog, for HIV pre-exposure prophylaxis (PrEP). In the study, one injection of low (150 mg/kg) or high dose (300 mg/kg) GS-CA1 or placebo (n=8 each) was given, followed by weekly escalating titer of rectal SHIV challenges for up to 15 weeks and then monitored to Week 24. Overall, 8/8 animals became infected in the placebo group, whereas 2/8 and 5/8 animals remained protected in the low and high dose GS-CA1 groups, resulting in an 86% (p=0.0061) and 96% (p=0.0002) infection risk reduction, respectively. Notably, treatment group infections occurred only after marked drug washout. These preclinical data demonstrate the potential utility of a long-acting capsid inhibitor to prevent HIV infection and may help advance clinical research evaluating lenacapavir as a potential future monotherapy option for HIV prevention.
Gilead previously announced plans to evaluate the use of lenacapavir as an injectable PrEP option administered every six months for cisgender adolescent girls and young women. An additional lenacapavir for PrEP study in cisgender men, persons of trans experience and gender non-binary individuals who have sex with men is planned. Both trials have projected initiation dates in 2021.
Additional lenacapavir data presented at virtual CROI 2021 provide insight into the investigational agent’s drug interaction potential, dosing response among people living with HIV with mild to moderate hepatic impairment, and resistance profile. Additional data from the CAPELLA study will be presented at a future scientific conference.
Lenacapavir is an investigational compound and is not approved by any regulatory authority for any use and its safety and efficacy are not known. There is no cure for HIV or AIDS.
About CAPELLA (NCT04150068)
CAPELLA is a Phase 2/3 randomized, double-blinded, placebo-controlled global multicenter study designed to evaluate the antiviral activity of Gilead’s investigational, long-acting HIV-1 capsid inhibitor, lenacapavir, in heavily treatment-experienced people with multi-drug resistant HIV-1 infection. CAPELLA includes men and women living with HIV and is being conducted at research centers in
In CAPELLA, 36 participants with multi-class HIV drug resistance and a detectable viral load while on a failing regimen were randomized 2:1 in a blinded fashion to receive oral lenacapavir or placebo for 14 days (randomized cohort), in addition to continuing their failing regimen (functional monotherapy). An additional 36 participants were enrolled to a non-randomized cohort. The primary endpoint is the proportion of participants in the randomized cohort achieving ≥ 0.5 log10 copies/mL reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period.
The study achieved its primary endpoint by demonstrating that a significantly higher proportion of participants in the randomized cohort receiving lenacapavir achieved a clinically meaningful viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those receiving placebo during the 14-day functional monotherapy period (88% vs. 17%, p<0.0001). Specifically, those who received lenacapavir (n=24) achieved statistically significantly greater mean decrease in viral load than those who received placebo (n=12) during the functional monotherapy period (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL, p<0.0001).
Following the 14-day functional monotherapy period, participants in the randomized cohort started open-label lenacapavir and an optimized background regimen, while those in the non-randomized cohort received open-label lenacapavir and an optimized background regimen on Day 1. This ongoing maintenance period of the study is evaluating the safety and efficacy of subcutaneous lenacapavir administered every six months in combination with an optimized background regimen.
Lenacapavir was generally well tolerated. The most common adverse events (AEs) observed to date in this study were injection site swelling (22%) and erythema (18%) and nodules (18%). Importantly, there were no serious AEs related to study drug and no AEs leading to discontinuation. Two participants experienced treatment-emergent capsid mutations and later re-suppressed while continuing lenacapavir.
For further information, please see https://clinicaltrials.gov/ct2/show/NCT04150068
Lenacapavir is an investigational, long-acting HIV-1 capsid inhibitor in development for the treatment and prevention of HIV infection. Lenacapavir's multi-stage mechanism of action profile is distinguishable from currently approved classes of antiviral agents and is designed to provide a new avenue for the development of long-acting regimens for people living with or at risk for HIV. While most antivirals act on just one stage of viral replication, lenacapavir is developed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance to other existing drug classes.
The safety, efficacy and dosing of lenacapavir are being evaluated in multiple ongoing clinical studies. Data presented at AIDS 2020 from the ongoing Phase 1 study support subcutaneous every six-month administration of lenacapavir for both HIV treatment and prevention studies. During IDWeek 2020, the company announced plans to evaluate the use of lenacapavir as an injectable PrEP option administered every six months among cisgender women, men who have sex with men and persons of trans experience. The trials have projected initiation dates in 2021.
For more than 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, and cure research. Today, millions of people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from ongoing and additional clinical trials, including those involving lenacapavir and GS-CA1, and the possibility that Gilead may be unable to complete one or more of such trials on the currently anticipated timelines or at all. In addition, it is possible that Gilead may make a strategic decision to discontinue development of lenacapavir and GS-CA1, or that FDA and other regulatory agencies may not approve lenacapavir and GS-CA1, and any marketing approvals, if granted, may have significant limitations on its use. As a result, lenacapavir and GS-CA1 may never be successfully commercialized. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These and other risks are described in detail from time to time in Gilead’s periodic reports filed with the
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