Sunlenca® Receives FDA Approval as a First-in-Class, Twice-Yearly Treatment Option for People Living With Multi-Drug Resistant HIV

Sunlenca is the First and Only Approved Capsid Inhibitor-Based HIV Treatment Option –

– New Drug Application Approval   Based on High Rates of Sustained Virologic Suppression in the CAPELLA Trial   –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced that Sunlenca ^® (lenacapavir), in combination with other antiretroviral(s) (ARV), has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in heavily treatment-experienced (HTE) adults with multi-drug resistant (MDR) HIV-1 infection. Sunlenca has a multi-stage mechanism of action distinguishable from other currently approved classes of antiviral agents and no known cross resistance exhibited in vitro to other existing drug classes. Sunlenca offers a new, twice-yearly treatment option for adults with HIV that is not adequately controlled by their current treatment regimen.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20221221005541/en/

Sunlenca Packaging (Photo: Business Wire)

"An effective antiretroviral regimen can be devised for most people living with the virus; however, some people living with HIV no longer have durable viral suppression due to resistance to multiple classes of antiretroviral therapies," said Sorana Segal-Maurer, MD, Director of the Dr. James J. Rahal Jr. Division of Infectious Diseases at NewYork-Presbyterian Queens, Professor of Clinical Medicine at Weill Cornell Medicine and the Site Principal Investigator for the CAPELLA trial. "The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced people with multi-drug resistant HIV. Following today's decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices."

Despite the significant advances in ARV therapy, there remain numerous critical and pressing unmet needs for people living with HIV. This is particularly true for individuals who are heavily treatment experienced – which account for an estimated 2% of adults living with HIV who are on treatment globally –- and are unable to maintain virologic suppression due to resistance, intolerance or safety considerations. This type of complexity further increases the chance of treatment failure, underscoring the need for new treatment options that are active against resistant variants of the virus with a novel mechanism of action.

Lenacapavir is a breakthrough innovation with the potential to be a preferred and versatile foundational long-acting agent due to its therapeutic potency and a range of dosing frequencies and routes of administration. Lenacapavir is being developed as a foundation for Gilead's future HIV therapies with the goal of offering several long-acting options that help address individual needs and preferences that may help optimize outcomes and reduce burden of care. Lenacapavir is being studied in multiple ongoing early and late-stage development programs and has the potential to offer a diverse set of person-centric options for treatment and prevention that could uniquely fit into the lives of people living with HIV and people who would benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established.

"This news is an important milestone in the work to help end the HIV epidemic as Sunlenca is now the only FDA-approved twice-yearly treatment for people with multi-drug resistant HIV," said Daniel O'Day, Chairman and Chief Executive Officer, Gilead Sciences. "Gilead scientists have developed a unique and potent antiretroviral medicine in Sunlenca with the potential for flexible dosing options. Our goal is to deliver multiple long-acting options for treatment and prevention that are tailored to the needs of people living with HIV and people who could benefit from PrEP medicines."

The FDA approval for Sunlenca is supported by data from the Phase 2/3 CAPELLA trial, which evaluated lenacapavir in combination with an optimized background regimen in people with multi-drug resistant HIV-1 who are heavily treatment experienced. CAPELLA participants had undergone previous treatment with a median of nine antiretroviral medications. In this patient population with significant unmet medical need, 83% (n=30/36) of participants randomly allocated to receive lenacapavir in addition to an optimized background regimen achieved an undetectable viral load ( Week 52 . Additionally, these participants achieved a mean increase in CD4 count of 82 cells/µL. These data were presented at the 29th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2022).

Sunlenca was reviewed and approved as a medication with FDA Breakthrough Therapy Designation, which is intended to expedite the development and review of new drugs which may demonstrate substantial improvement over available therapy. 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.

Lenacapavir, alone or in combination, is not approved by any regulatory authority outside of the United States, United Kingdom, Canada or the European Union for any use. The European Marketing Authorization applies to all 27 member states of the European Union, as well as Norway, Iceland and Liechtenstein.

Additional regulatory filings and decisions by regulatory authorities are anticipated to continue in 2023.

The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. Gilead is studying the safety and efficacy of lenacapavir for HIV prevention in multiple ongoing clinical studies.

Please see below for the U.S. Indication and Important Safety Information for Sunlenca.

There is no cure for HIV or AIDS.

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

About CAPELLA (NCT04150068)

CAPELLA is a Phase 2/3, double-blinded, placebo-controlled global multicenter study designed to evaluate the antiviral activity of lenacapavir administered every six months as a subcutaneous injection in heavily treatment-experienced people with multi-drug resistant HIV-1 infection. CAPELLA includes men and women with HIV-1 and is being conducted at research centers in North America, Europe and Asia.

In CAPELLA, 36 participants with multi-class HIV-1 drug resistance and a detectable viral load while on a failing regimen were randomly allocated to receive oral lenacapavir or placebo in a 2:1 ratio for 14 days, in addition to continuing their failing regimen (functional monotherapy). An additional 36 participants were enrolled in a separate treatment cohort. Both cohorts are part of the ongoing maintenance period of the study evaluating the safety and efficacy of subcutaneous lenacapavir administered every six months in combination with an optimized background regimen. The primary endpoint was the proportion of participants randomly allocated to receive lenacapavir or placebo for 14 days, in addition to continuing their failing regimen, achieving ≥0.5 log10 copies/mL reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period. The study found that 88% of participants receiving lenacapavir (n=21/24) experienced at least a 0.5 log10 reduction in HIV-1 viral load by the end of 14 days of functional monotherapy as compared with 17% of those receiving placebo (n=2/12).

Following the 14-day functional monotherapy period, participants randomly allocated to receive lenacapavir or placebo, in addition to continuing their failing regimen, started open-label lenacapavir and an optimized background regimen, while those enrolled in a separate treatment cohort received open-label lenacapavir and an optimized background regimen on Day 1. This ongoing maintenance period is evaluating the additional study endpoints of safety and efficacy of subcutaneous lenacapavir administered every six months in combination with an optimized background regimen.

The New England Journal of Medicine published the primary outcome results of the CAPELLA study in its May 11, 2022 issue - Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection .

For further information, please see https://clinicaltrials.gov/ct2/show/NCT04150068 .

About Sunlenca ^®

Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) is a first-in-class, long-acting HIV capsid inhibitor approved in the United States, the United Kingdom, Canada and the European Union, for the treatment of HIV infection, in combination with other antiretroviral(s), in people with multi-drug resistant HIV who are heavily treatment-experienced. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option. The multi-stage mechanism of action of Sunlenca is distinguishable from other currently approved classes of antiviral agents and is designed to provide a new avenue for the development of a long-acting treatment option for individuals with multi-drug resistant HIV whose virus no longer effectively responds to therapy. While most antivirals act on just one stage of viral replication, Sunlenca is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Sunlenca is the only HIV treatment option administered twice-yearly.

U.S. Indication for Sunlenca

Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

U.S. Important Safety Information for Sunlenca

Contraindications

• Coadministration : Concomitant administration of SUNLENCA is contraindicated with strong CYP3A inducers.

Warnings and precautions

• Immune reconstitution syndrome , including the occurrence of autoimmune disorders with variable time to onset, has been reported in patients treated with combination antiretroviral (ARV) therapy.
• Long-acting properties and potential associated risks with SUNLENCA : Residual concentrations of SUNLENCA may remain in the systemic circulation of patients for up to 12 months or longer. SUNLENCA may increase exposure, and potential risk of adverse reactions, to drugs primarily metabolized by CYP3A initiated within 9 months after last injection. Counsel patients regarding the dosing schedule because nonadherence could lead to loss of virologic response and development of resistance. If virologic failure occurs, switch to an alternative regimen if possible. If discontinuing SUNLENCA, begin alternate suppressive ARV regimen within 28 weeks from last injection.
• Injection site reactions may occur, and nodules and indurations may be persistent.

Adverse reactions

• Most common adverse reactions (incidence ≥3%, all grades) are injection site reactions (65%) and nausea (4%).

Drug interactions

• Prescribing information : Consult the full prescribing information for SUNLENCA for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
• Enzymes/transporters : Drugs that are strong or moderate inducers of CYP3A may significantly decrease the concentration of SUNLENCA. Drugs that strongly inhibit CYP3A, P-gp, and UGT1A1 together may significantly increase the concentration of SUNLENCA. SUNLENCA may increase the exposure of drugs primarily metabolized by CYP3A, when initiated within 9 months after the last injection of SUNLENCA, which may increase the potential risk of adverse reactions.

Dosage and administration

• Dosage : Initiation with 1 of 2 options, followed by maintenance dosing once every 6 months. Tablets may be taken with or without food.
  • Initiation Option 1 : Day 1: 927 mg by subcutaneous injection and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets).
  • Initiation Option 2 : Day 1: 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets). Day 8: 300 mg orally (1 x 300-mg tablet). Day 15: 927 mg by subcutaneous injection.
  • Maintenance : 927 mg by subcutaneous injection every 26 weeks +/- 2 weeks from date of last injection.
• Missed Dose : During the maintenance period, if more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue SUNLENCA treatment, restart the initiation dosage regimen from Day 1, Option 1 or Option 2.

Pregnancy and lactation

• Pregnancy : There is insufficient human data on the use of SUNLENCA during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established.
• Lactation : Individuals infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

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.

For 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV infection, and the first, long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a preventable, chronic condition for millions of people.

Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships and collaborations, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as the number one philanthropic funder of HIV-related programs in a report released by Funders Concerned About AIDS.

Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

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 Gilead's ability to initiate, progress and complete clinical trials in the anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Sunlenca (lenacapavir); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that additional regulatory authorities may not approve lenacapavir in a timely manner or at all; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing Sunlenca; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, as filed with the U.S. Securities and Exchange Commission. 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. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is 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 and disclaims any intent to update any such forward-looking statements.

U.S. Prescribing Information for Sunlenca is available at www.gilead.com .

Sunlenca, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company's website at www.gilead.com ,   follow Gilead on Twitter ( @Gilead Sciences ) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

View source version on businesswire.com: https://www.businesswire.com/news/home/20221221005541/en/

Jacquie Ross, Investors
investor_relations@gilead.com

Meaghan Smith, Media
public_affairs@gilead.com