Gilead’s Investigational Lenacapavir Demonstrates Sustained Long-Acting Efficacy Through Week 26 in Data Presented at CROI

“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 Diana Brainard, MD, Senior Vice President, Virology Therapeutic Area, Gilead Sciences. “When treated with lenacapavir plus an optimized background regimen in this study, the majority of participants achieved virologic suppression at 26 weeks of treatment. These interim results from the CAPELLA trial demonstrate lenacapavir’s potential to be a foundational, long-acting agent of future HIV treatment regimens.”

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 May 2019, the FDA granted Breakthrough Therapy Designation for the development of lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs.

“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 Sorana Segal-Maurer, MD, Director of the Dr. James J. Rahal Jr. Division of Infectious Diseases at NewYork-Presbyterian Queens and the Site Principal Investigator for the CAPELLA study. “These challenges highlight a true unmet need and underscore the importance of new treatment options for heavily treatment‐experienced people living with multi-drug resistant HIV, for whom it is otherwise not possible to construct a suppressive antiviral regimen. The CAPELLA results show lenacapavir’s potential value as a long-acting option that can be administered subcutaneously every six months, and as part of a complete treatment regimen to provide viral suppression and overcome resistance for many patients in this important population.”

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 North America, Europe and Asia.

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

About Lenacapavir

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.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

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.

Forward-Looking Statement

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 U.S. Securities and Exchange Commission, including current reports on Form 8-K, quarterly reports on Form 10-Q and annual reports on Form 10-K. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and are cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

Sorana Segal-Maurer, MD, is a paid consultant for Gilead Sciences, Inc.

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