New Biktarvy® Data Presented at IAS 2023 Further Demonstrate Safety and Efficacy Profile in a Broad Range of People and Communities Affected by the Global HIV Epidemic

– Biktarvy Evaluated in a Diverse Range of People With HIV, Including Pregnant Women and Pediatric Populations –

– 96-Week Data from ALLIANCE Trial Show Durability of Biktarvy in Adults With HIV and HBV Coinfection –

FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from multiple studies reinforcing Biktarvy^® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) as a treatment option for a broad range of people with HIV. The latest findings include key insights into the treatment of virologically suppressed pregnant women and children two years of age or older (weighing at least 14 kg to less than 25 kg) and positive Week 96 data from the ALLIANCE trial in adults with HIV/hepatitis B (HBV) coinfection who were initiating therapy. 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.

Pregnant Women with HIV

In an open-label study evaluating the pharmacokinetics, safety, and efficacy of switching to once-daily Biktarvy in virologically suppressed pregnant women with HIV, Biktarvy was generally well tolerated and all participants maintained virologic suppression at delivery (HIV-1 RNA <50 copies/mL; n=32). Moreover, no cases of perinatal HIV transmission were observed. No adverse events (AEs) leading to premature discontinuation and no drug-related AEs were observed in the pregnant women or neonates. These results suggest Biktarvy may be an appropriate treatment option during pregnancy with no dose change required.

“This study demonstrates the potential role of B/F/TAF as a treatment of HIV in pregnant women, a population that has historically been difficult to study and that continues to have significant needs,” said Anchalee Avihingsanon, MD, PhD, Senior Researcher, HIV–NAT, Thai Red Cross AIDS Research Center, Thailand. “The clinical profile of Biktarvy is further supported by safety data and no mother-to-child transmission in this study and data showing that normal dosing may be appropriate. These are important findings for pregnant women and their healthcare providers when considering HIV treatment.”

Pediatric HIV

Additional Biktarvy data presented at IAS 2023 included an analysis of two ongoing, open-label studies evaluating the weight, height, body mass index (BMI) and lipid metabolism parameters of virologically suppressed children with HIV (81.6% Black; aged ≥2 years and weighing 14 to <25 kg) who switched to Biktarvy (n=22) or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; n=27). At Week 48, the proportion of participants who were underweight decreased from 20.4% to 14.3%, while the proportion of normal weight participants increased from 67.3% to 73.5%, respectively. Meanwhile, the proportion of overweight or obese participants remained stable at 12.2%. Overall, lipid metabolism parameters generally improved during 48 weeks of treatment. Presently, children with HIV must be on antiretroviral therapy for their entire lives. This underscores the importance of studying the impacts of treatment on weight, height, body mass index and lipid parameters in this young age group.

“It is important that we limit the potential for weight and metabolic changes as a result of antiretroviral treatment in young children with HIV,” said Eva Natukunda, MD, Head of Department of Pediatrics, Joint Clinical Research Centre, Uganda. “In this study, the results of the TAF-based regimens further reinforce the role of these regimens as an appropriate treatment option for this population.”

In October 2021, the U.S. Food and Drug Administration (FDA) approved a low-dose tablet dosage form of Biktarvy for pediatric patients weighing at least 14 kg to less than 25 kg who are virologically suppressed or new to antiretroviral therapy. In the EU, Biktarvy is authorized for the treatment of HIV infection in adults and pediatric patients at least 2 years of age and weighing at least 14 kg without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir.

HIV/HBV Coinfection

ALLIANCE is an ongoing Phase 3 study evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV-1/HBV co-infection initiating treatment. The Week 96 results demonstrated the efficacy of both antiretroviral regimens. Participants who initiated treatment with Biktarvy (n=121) or DTG+F/TDF (n=122) had similarly high and sustained rates of viral suppression. These data, combined with the lower impact of TAF versus TDF on bone and renal parameters, show clinical benefits of Biktarvy for adults with both HIV-1 and HBV initiating antiviral therapy.

The Week 96 results show numerically higher levels of hepatitis B viral suppression (HBV DNA <29 IU/mL) with Biktarvy (75% vs. 70%; 95% CI – 8.3%,13.4%, p=0.64). Importantly, participants who initiated treatment with Biktarvy had numerically higher alanine aminotransferase (ALT) normalization (72% vs 57%, p=0.13) and hepatitis B surface antigen loss (23% vs. 14%, p=0.066) and seroconversion (9% vs. 7%, p=0.44). Expectedly, participants who initiated treatment with Biktarvy or DTG+F/TDF also had high rates of HIV suppression (HIV-1 RNA <50 copies/mL) at Week 96 (87% vs. 88%; 95% CI – 8.9% to 8.3%, p=0.94) with mean CD4 cell count increases of 261 and 229 cells/μl from baseline, respectively. Beyond Week 96, select participants will be able to receive Biktarvy in an open-label extension phase for up to 48 weeks.

Further results from the trial showed that safety findings were similar between the Biktarvy and DTG+F/TDF groups. Adverse events (AEs) included upper respiratory tract infection (19.8% vs. 14.8%), COVID-19 (38% vs. 36.1%), pyrexia (12.4% vs. 13.1%), ALT increase (8.3% vs. 12.3%), and nasopharyngitis (12.4% vs. 6.6%).

“Gilead is committed to the treatment of HIV in a broad range of people with diverse health needs, which is a cornerstone of our global efforts to help end the epidemic,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “These studies build on our understanding of Biktarvy and its role in helping people affected by HIV by providing clinically relevant treatment data for pregnant women, children and those living with comorbidities like HBV.”

The use of Biktarvy in individuals with HIV/HBV co-infection is investigational and the safety and efficacy of this use have not been established.

Please see below for U.S. Indications and Important Safety Information, including Boxed Warning on post treatment acute exacerbation of hepatitis B, for Biktarvy.

There is currently no cure for HIV or AIDS.

About ALLIANCE (NCT03547908)

ALLIANCE is a Phase 3, randomized, double-blind study designed to evaluate the safety and efficacy of Biktarvy or DTG+F/TDF (with placebo) in adults initiating treatment for HIV/hepatitis B (HBV) co-infection. The primary endpoints evaluated the proportion of adults with HIV-1 RNA suppression (<50 copies/mL) and proportion of adults with plasma HBV DNA suppression (<29 IU/mL) at Week 48. Secondary endpoints will include efficacy of Biktarvy versus DTG+F/TDF by achievement of HIV-1 RNA suppression (<50 copies/mL), HBV DNA suppression (< 29 IU/mL), and the safety and tolerability profile of the two treatment groups at Week 96. At Week 48 and Week 96, ALT normalization, and hepatitis B surface antibody (HBsAg) loss are evaluated.

The primary outcome results of the Alliance study were presented at the 24th International AIDS Conference (AIDS 2022).

The Lancet HIV published the 96-week findings of the Alliance study in its July 24, 2023 issue – The ALLIANCE study: a phase 3, randomised, double-blind, multicentre, non-inferiority study of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection

For further information, please see https://clinicaltrials.gov/ct2/show/NCT03547908

About Biktarvy

Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir, with the Descovy^® (emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, F/TAF) backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines.

U.S. Indication for Biktarvy

Biktarvy is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.

U.S. Important Safety Information for Biktarvy

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

• Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

Contraindications

• Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Warnings and precautions

• Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions.
• Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
• New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
  
  Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus.

• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions

• Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).

Drug interactions

• Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
• Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1.
• Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration

• Dosage: Adult and pediatric patients weighing ≥25 kg: 1 tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1 tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily with or without food. For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes.
• Renal impairment: For patients weighing ≥25 kg, not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history. For patients weighing ≥14 kg to <25 kg, not recommended in patients with CrCl <30 mL/min.
• Hepatic impairment: Not recommended in patients with severe hepatic impairment.
• Prior to or when initiating: Test patients for HBV infection.
• Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

Pregnancy and lactation

• Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
• Lactation: Women 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 or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Biktarvy; uncertainties relating to regulatory applications for Biktarvy and related filing and approval timelines, including potential applications for indications currently under investigation; Gilead’s ability to receive regulatory approvals in a timely manner or at all, and the risk that any such approvals, if granted, may have significant limitations on its use; the risk that physicians may not see the benefits of prescribing Biktarvy; 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. Prescribing Information for Biktarvy, including BOXED WARNING, is available at www.gilead.com.

Biktarvy, 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.

Contacts

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Meaghan Smith, Media

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