– Patient-Reported Outcomes From the CAPELLA Trial Align With the Demonstrated Safety and Tolerability Profile of Lenacapavir –

– Analyses Show Oral Bridging Maintains Virologic Suppression When Subcutaneous Lenacapavir Doses are Missed –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today presented new data reinforcing the efficacy, safety, and tolerability profile of lenacapavir, including patient-reported outcomes (PRO) from the Phase 2/3 CAPELLA trial. These latest findings underscore the role of lenacapavir, the first long-acting injectable HIV treatment medication administered twice-yearly, as a person-centric therapy option and its transformative potential impact on the future of coordinated HIV clinical care. The data were presented at the 12th International AIDS Society (IAS) Conference on HIV Science (IAS 2023), taking place July 23-26 in Brisbane, Australia.

Using five validated scoring instruments measuring health-related quality of life components including physical and mental health, CAPELLA participants (n=64/72) reported favorable scores at Week 52 and with relative consistency over the time period. These reflect values that are similar to that of the general U.S. population. Separate analyses from the Phase 2/3 CAPELLA and Phase 2 CALIBRATE trials showed weekly oral lenacapavir, when paired with an OBR, led to high rates of virologic suppression and high, efficacious concentrations of lenacapavir in the blood in study participants when the administration of subcutaneous lenacapavir was interrupted.

“Understanding potential real-world use of novel HIV options is essential to helping ensure they have the greatest potential impact,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “The patient-reported outcome data presented at IAS 2023 provide deep insight into the tolerability of lenacapavir, and the oral bridging data helps demonstrate how twice-yearly lenacapavir can fit into people’s lives. As we continue development of lenacapavir-based options with the goal to optimize HIV treatment, people’s experience and insights are at the center.”

People with HIV who are heavily treatment-experienced may experience symptoms that negatively affect their health-related quality of life, including mobility, self-care, mental health, and physical pain, which could impact their adherence to HIV treatment. Patient-reported outcomes through Week 52 from the CAPELLA study were gathered from five validated instruments that assess quality of life: the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) index, EQ-5D-5L visual analogue scale (VAS), Short Form-36 (SF-36), HIV Symptom Index (HIV-SI), and Numeric Pain Rating Scale (NPRS). Of the 72 enrolled participants, 64 reported outcomes through Week 52, with notable stability in scores at baseline through Week 52 and generally reflective of the U.S. population norms (see table below). These data demonstrate lenacapavir plus OBR has the potential to be an effective HIV regimen without compromising health-related quality of life.

Additional analyses from CAPELLA and CALIBRATE provided insight on lenacapavir’s potential to maintain high rates of efficacious concentrations, virologic suppression, and tolerability when combined with an OBR after missed doses of subcutaneous lenacapavir, and when supplemented with a weekly oral bridging (OB) dose. 79% (57/72) of CAPELLA participants and 78% (82/105) of CALIBRATE participants received an OB dose of lenacapavir (300 mg, once-weekly) on average for 19 weeks, with an adherence rate (by pill count) of ≥95% in most participants.

At Week 10, 20, and Week 30 in a missing equals excluded analysis, 98% (44/45), 97% (30/31), and 100% (10/10), respectively, of participants on OB in CAPELLA who had been virologically suppressed remained virologically suppressed. In CALIBRATE, in a missing equals excluded analysis, 100% of all participants at Week 10, 20, and 30 were virologically suppressed (77/77; 58/58; 5/5, respectively). One CAPELLA participant who missed two non-consecutive oral lenacapavir doses did not maintain virologic suppression during OB. Through the Week 30 OB period, mean plasma concentrations of lenacapavir were maintained above effective concentration (inhibitory quotient-4), indicating 300 mg, once-weekly lenacapavir + OBR may provide concentrations high enough to bridge a missed dose of twice-yearly subcutaneous lenacapavir injection. The use of lenacapavir for oral bridging is not approved by any regulatory authority.

Overall, OB demonstrated a consistent safety and tolerability profile, with treatment-emergent adverse events (AEs) similar to subcutaneous lenacapavir. Two participants in CAPELLA (3.5%) and one participant in CALIBRATE (1.2%) experienced treatment-related diarrhea.

“As clinicians, we seek to understand the real-world constraints people living with the virus may experience with their HIV treatment regimen, and how scenarios when people are unable to receive their next scheduled injection dose could impact their treatment success,” said Jean-Michel Molina, MD, Université Paris Cité, Professor of Infectious Diseases and Head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals. “Results from this analysis provide support for the future potential use of oral therapy with lenacapavir as a treatment strategy to maintain virologic suppression in patients between planned or otherwise missed injection dosing visits in clinical practice.”

Twice-yearly lenacapavir is being developed as a foundation for future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination with other antiretroviral agents for treatment or as a single agent for prevention, that could help address individual needs and preferences of people with HIV and people who would benefit from PrEP. The use of twice-yearly lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. Twice-yearly lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead's prevention and treatment research program.

Sunlenca^® (lenacapavir), alone or in combination, is not approved by any regulatory authority for any use outside of Australia, Canada, the European Union, Israel, Switzerland, the United Arab Emirates, the United Kingdom or the United States.

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

There is no cure for HIV or AIDS.

About Sunlenca

Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor indicated 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 is the only HIV treatment option administered twice-yearly. 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’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. 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.

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, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

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 treatable, 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.

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 lenacapavir; uncertainties relating to regulatory applications and related filing and approval timelines; Gilead’s ability to receive regulatory approvals in a timely manner or at all, and the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; 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 March 31, 2023, 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. full 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.

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