Biktarvy® Demonstrates High Rates of Viral Suppression in People With HIV and Comorbidities

– New Data Evaluating the Efficacy and Safety Profile of Biktarvy for the Treatment of People with HIV and Hepatitis B or Tuberculosis will be Presented –

– Retrospective Analysis Evaluating HIV Resistance-Associated Mutations Reinforces Importance of Treatment Selection in HIV Management –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from three studies evaluating the efficacy and safety profile of Biktarvy^® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) for a broad range of people with HIV, including those with HIV/hepatitis B (HBV) coinfection and HIV/tuberculosis (TB) coinfection. These data and other studies supporting the important role of Biktarvy in the HIV treatment landscape were presented at the 31st Conference on Retroviruses and Opportunistic Infections (CROI).

“People with HIV and comorbid conditions or pre-existing treatment resistance can often face complex and evolving treatment needs. These studies were conducted to help bridge the unmet HIV treatment gap and better understand the potential of Biktarvy in a broad range of people and communities affected by HIV and their diverse health needs, said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “The data presented at CROI contribute to the growing body of long-term evidence for Biktarvy and reinforce Gilead’s commitment to a person-centric approach to HIV treatment research.”

HIV/HBV Coinfection

ALLIANCE (NCT03547908) is an ongoing Phase 3 study evaluating the efficacy and safety of Biktarvy compared to dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV/HBV coinfection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV /HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported Week 96 results demonstrated the efficacy of both antiretroviral regimens. Additionally, ALLIANCE participants treated with Biktarvy exhibited numerically higher levels of HBV viral suppression and seroconversion. 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%).

A new exploratory analysis presented at CROI further investigated the factors associated with the HBV treatment response observed with Biktarvy compared to DTG+F/TDF. This subgroup analysis compared the HBV treatment responses according to baseline demographics, HBV genotype, and markers of HIV-1/HBV disease severity for all participants (n=243) at two years.

Consistent with the overall population, the present analysis suggests that in people with HIV/HBV coinfection, the treatment response of TAF- versus TDF-based therapy for many HBV treatment outcomes may be greater for certain subgroups, supporting the continued evaluation of Biktarvy in this population. Some of the subgroups that showed treatment differences favoring Biktarvy included younger age, those with certain levels or types of HBV DNA/genotypes and those with higher-than-normal liver enzymes, among others. The use of Biktarvy in individuals with HIV/HBV is investigational, and the safety and efficacy of this use have not been established.

HIV/TB Coinfection

TB is the leading cause of death among people with HIV. In 2022, approximately 167,000 people died from HIV-associated TB, with the WHO African Region having the highest prevalence. While significant progress has been made in early detection and treatment of HIV-associated TB, there are still significant therapeutic challenges. The interactions between antiretrovirals and TB medications complicate the management of individuals with dual infections. These interactions primarily occur during the metabolism of the drugs. The drug-drug interactions involving the first-line TB drug, rifampicin, are particularly clinically relevant for a number of antiretroviral agents.

Integrase strand transfer inhibitors (INSTIs) are recommended by major standard guidelines for HIV treatment. Several clinical research gaps exist when combining the INSTIs and drugs used for the treatment of tuberculosis, which need to be addressed to inform HIV and tuberculosis co-treatment. INSIGHT (NCT04734652) is an ongoing Phase 2b open-label study conducted in collaboration with a range of organizations, including the Centre for the AIDS Programme of Research in South Africa (CAPRISA), investigating the efficacy, safety, and pharmacokinetics of Biktarvy and dolutegravir 50 mg (DTG) + lamivudine 300mg/ tenofovir disoproxil fumarate 300mg, TLD, in adults initiating treatment for HIV/TB coinfection who have been receiving a rifampicin-based treatment regimen for at least eight weeks.

Participants were randomly allocated to receive Biktarvy or TLD in a 2:1 ratio. Biktarvy was taken twice a day during rifampicin-containing TB treatment and 2 weeks after stopping TB treatment. Thereafter, Biktarvy was taken once daily. Once-daily TLD plus dolutegravir 50mg evening dose was taken during TB treatment and for two weeks after completion of TB treatment. Thereafter, TLD was taken once daily – as per standard of care, until 48 weeks. The primary outcome measure is viral suppression rates at Week 24, defined as HIV-1 RNA ˂50 copies/mL.

Preliminary week 24 results presented at CROI showed that 97% percent (71/73) of participants treated with Biktarvy achieved viral suppression (HIV-1 RNA < 50 copies /ml) as did 97% (36/37) of participants treated with the DTG-based regimen. Serious adverse events (AEs) were common in this population with advanced HIV disease and TB. However, none of the reported AEs were deemed related to the study drug. A similar number of Grade 3 and Grade 4 AEs were reported in both arms.

“South Africa has the largest HIV epidemic in the world, with more than 7 million people with HIV, over half of whom have latent TB co-infection,” said Anushka Naidoo, BPharm, MMedSc, PhD, Research Scientist, Centre for AIDS Programme of Research in South Africa (CAPRISA), and Principal Investigator of the INSIGHT study. “The availability of antiretroviral therapy options, including within drug classes, is important, particularly in high HIV/TB burden settings. The key findings from this landmark study presented at CROI support the continued evaluation of Biktarvy in people with HIV and TB as a potential treatment to bridge a critical gap for the individuals and communities who bear the disproportionate burden of co-infection."

The INSIGHT trial will continue through Week 48 to determine longer-term safety and efficacy. Biktarvy is contraindicated for coadministration with rifampin, also known as rifampicin, by the U.S. FDA. The use of Biktarvy in individuals with HIV/TB coinfection is investigational, and the safety and efficacy of this use have not been established.

Resistance-Associated Mutations in Switch Trials

Genetic changes occur in HIV by chance. Some of these changes stop HIV medicines from working; these changes are called resistance mutations. To understand the length of time that resistance mutations stay in the body, researchers looked at the genetic patterns of HIV (called HIV genotype) over time in people who took part in three clinical studies.

Genotype data were collected at the beginning of the clinical trials, and for some participants, earlier genotyping reports were also available. Researchers looked at these reports to find out whether resistance mutations persisted, newly appeared, or disappeared in a cohort of participants (n=242) from three trials who switched to Biktarvy treatment after achieving viral suppression for at least three months on their previous antiretroviral regimen.

The majority of resistance-associated mutations in the analysis were detected 100% of the time or were newly detected and did not disappear over time. Drug resistance mutations archived in cells may persist despite viral suppression, posing a risk for transmission of drug-resistant virus in cases of virological failure, treatment interruption or non-adherence. Healthcare providers must consider all previous drug treatments and genotype reports and should not assume that resistance mutations are no longer present simply because they are not reported in the most recent genotype report, as they may reemerge at a later time. These findings highlight the importance of understanding an individual's treatment history and prior resistance mutation status for treatment management.

In February 2024, the U.S. FDA approved a new, expanded indication for Biktarvy to treat virologically suppressed people with HIV with M184V/I resistance, a common form of treatment resistance.

Additional research studies evaluating Biktarvy presented at CROI 2024 explore safety and efficacy data in older populations, as well as treatment effects on immune activation biomarkers and weight change in people with HIV who are virologically suppressed.

Please see below for U.S. Indications and Important Safety Information for Biktarvy, including BOXED WARNING.

There is currently no cure for HIV or AIDS.

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 (ARV) treatment history or to replace the current ARV regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir.

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 in HIV

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 more than 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 help reduce new HIV infections, 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, collaborations and charitable giving, 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.

Learn more about Gilead’s unique collaborations worldwide and the work to help end the global HIV epidemic.

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 and related filing and approval timelines, including potential applications for indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 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) and LinkedIn, or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

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