• Three-Year Outcomes from the BICSTaR Study Further Demonstrate the Consistent Efficacy and Safety Profile of Biktarvy, Providing Insights for HIV Clinical Care 

FOSTER CITY, Calif. / Oct 19, 2023 / Business Wire / Gilead Sciences, Inc. (Nasdaq: GILD) announced today new long-term real-world data from the BICSTaR study highlighting the safety and efficacy profile of Biktarvy^® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) as a treatment regimen for a broad range of people with HIV, including those with a prior treatment history or comorbidities. These findings were presented at the 19th European AIDS Conference (EACS 2023), taking place October 18-21 in Warsaw, Poland.

“HIV affects a wide range of people so understanding a treatment’s efficacy and safety profile through real-world studies can help further inform HIV clinical care. The goal of the BICSTaR study is to provide us with a more comprehensive understanding of Biktarvy and its role in clinical practice,” said Michael Sabranski, MD, presenting author and physician at the ICH Study Center, Hamburg, Germany. “The three-year outcomes from the BICSTaR study further support the real-world profile of Biktarvy in a diverse range of people with HIV, and these findings align with evidence from randomized clinical trials of Biktarvy treatment.”

New real-world data from the ongoing, multinational, observational, real-world BICSTaR study were collected from individuals with HIV who were enrolled in Canada, France, and Germany. Overall, Biktarvy was found to be highly effective for trial participants after three years of follow-up, with 97% (58/60) of treatment-naïve and 97% (356/367) of treatment-experienced participants virologically suppressed (HIV-1 RNA <50 copies/mL; missing=excluded analysis). Additionally, there were no reports of treatment-emergent resistance.

Overall, 10%, 2% and <1% of participants had any drug-related adverse events (DRAEs) across years one, two, and three respectively, with the most commonly reported DRAEs being weight change (2%) and depression (1%). Numerically small median changes in estimated glomerular filtration rate (eGFR) and stable total cholesterol to high-density lipoprotein (TC:HDL) ratios were observed in both treatment-naive and treatment-experienced participants over the three-year period. Among study participants, the median change in weight from baseline to three years was +4.3kg for treatment-naïve participants and +1.7kg for treatment-experienced participants. These findings are consistent with previously presented data. Initiation of therapy generally leads to weight change in people with HIV who have no prior treatment history, which is partially attributable to a return-to-health effect. Few participants (7%) discontinued Biktarvy due to DRAEs, with most discontinuations occurring in the first year.

Mental health outcomes reported by treatment-experienced participants with pre-existing symptoms of depression, anxiety or insomnia in BICSTaR were also presented at EACS 2023. Rates of mental health conditions are higher among people with HIV compared to the general population. Mental health impairments can further increase the risk of negative health outcomes at every stage of the HIV care continuum. In this cohort of people with HIV who were receiving comedications for pre-existing mental health impairments and switched their treatment to Biktarvy, viral loads were assessed at baseline and 24 months. The rates of virologic suppression remained high over the 24-month period. In a missing=excluded analysis, 94% (88/94) of participants were virologically suppressed (HIV-1 RNA <50 copies/mL) at two years. Self-reported symptoms associated with depression, anxiety, or insomnia remained stable over the course of treatment with Biktarvy, with small, numerical increases in Mental Health Component Summary score and treatment satisfaction. Drug-related adverse events of depression, anxiety, or insomnia were reported in 6% (7/123), which led to discontinuation of the study drug in four participants. No serious adverse events of depression, anxiety, or insomnia were reported.

The results underline the importance of patient-reported outcomes as a person-centered approach to HIV research and can help us to better understand the impact on health-related quality of life and specifically, mental health status of people with HIV. This could help inform treatment strategies for these groups.

"The latest findings from the BICSTaR study provide a firsthand assessment of the impact of HIV treatment and care on individuals living with HIV, including those with mental health conditions. The results presented at EACS complement the results observed in multiple Phase 3 clinical trials, which demonstrate the sustained efficacy, safety profile, and high barrier to resistance of Biktarvy," said Fernando Bognar, MD, Vice President of Global Medical Affairs for HIV at Gilead Sciences. "Real-world evidence and observational studies can help bridge the gap between clinical trials and clinical practice, providing valuable insights into the characteristics of individuals with HIV in specific regions or communities, particularly those historically underrepresented in HIV clinical research."

Additional research studies evaluating Biktarvy include a pooled analysis of nine Phase 3 randomized studies in treatment-naïve and virologically suppressed people with HIV who were restarting treatment with Biktarvy after experiencing virologic rebound. Out of the total participants (3,772), 2.5% (96/3,772) experienced virologic rebound, resulting in 110 virologic rebound events. Virologic rebound events were defined as having a viral load of 1,000 copies per mL or higher after achieving virologic suppression. When excluding events where the outcome could not be evaluated due to the rebound occurring at the last assessment, the resuppression rate was 93% (91/98).

The study found that the majority of participants who experienced virologic rebound achieved viral resuppression within 30 days after regaining virologic control. No instances of treatment-emergent resistance were observed in participants with persistent viremia. These findings support the ongoing evaluation of Biktarvy as a potential treatment option for individuals with viremia who had previously achieved virologically suppressed and restarting treatment. The use of Biktarvy in patients with a history of treatment failure is investigational and the safety and efficacy of this use has not been determined.

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 the BICSTaR Study

The Bictegravir Single Tablet Regimen (BICSTaR) study is an ongoing, multinational, observational single-arm, non-comparative real-world cohort study, which aims to evaluate the effectiveness, safety, tolerability, and patient-reported outcomes of treatment with Biktarvy in treatment‐naïve and treatment‐experienced people with HIV. Among the people with HIV enrolled in the BICSTaR study, there is a high baseline prevalence of comorbidities.

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.

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; 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 June 30, 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.