Biktarvy® Demonstrates High Efficacy for a Broad Range of People Initiating Treatment for HIV, Including Those With HBV Coinfection

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results reinforcing Biktarvy^® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) as a highly efficacious treatment option for a broad range of people with HIV, including individuals with HIV/hepatitis B (HBV) coinfection. Interim data from the ALLIANCE trial evaluating Biktarvy in adults with HIV/HBV coinfection who were initiating therapy show potential suppression of HBV and HIV suppression comparable to an alternative HIV regimen. Additionally, 5-year data from two Phase 3 trials further demonstrated Biktarvy’s sustained efficacy, safety profile and high barrier to resistance in adults with HIV initiating therapy. The data were presented at the 24th International AIDS Conference (AIDS 2022).

Data from the ALLIANCE trial, which is an ongoing Phase 3 trial evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, demonstrated the efficacy of both antiretroviral regimens, in adults with HIV/HBV co-infection initiating treatment. The Week 48 results show Biktarvy demonstrated superior HBV DNA suppression. Importantly, participants who initiated treatment with Biktarvy versus DTG+F/TDF demonstrated superior HBV DNA suppression (<29 IU/mL) (63% vs. 43%, p=0.0023) and hepatitis B e-antigen (HBeAg) seroconversion (23% vs. 11%, p=0.031). The Week 48 results also showed that participants who initiated treatment with Biktarvy or DTG+F/TDF both had similarly high rates of HIV suppression (HIV-1 RNA <50 copies/ml). Participants who initiated treatment with Biktarvy or DTG+F/TDF both had high rates of HIV suppression at Week 48 (95% vs. 91%; 95% CI - 2.5% to 10.8%, p=0.21) with mean CD4 cell count increases of 200 and 175 cells/μl from baseline, respectively. The ALLIANCE trial will continue in a blinded fashion through Week 96 to determine longer-term safety and efficacy.

HIV/HBV coinfection is a major global public health threat that increases the morbidity and mortality beyond either infection alone. HBV impacts approximately 8% of people with HIV globally, and HIV/HBV coinfection rates can reach 25% in areas where both viruses are endemic, such as Asia. In some parts of Asia, HBV is endemic with a projected 70% of the population showing serologic evidence of current or prior infection. Because each virus affects the other’s natural history and response to therapy, HIV/HBV co-infection requires dedicated research.

“ALLIANCE is a landmark clinical trial, investigating the specific treatment responses of adults with HIV/HBV co-infection,” said Anchalee Avihingsanon, MD, PhD, Senior Researcher, HIV–NAT, Thai Red Cross AIDS Research Center, Thailand. “Emerging HIV epidemics in areas of high HBV rates such as Asia are expanding the number of people with HIV/HBV coinfection. This inclusive and representative study enrolled and treated participants from 11 different geographies with 88% of participants of Asian descent, driving the availability of data from within those communities most impacted.”

The multi-center ALLIANCE trial enrolled participants (n=243: Biktarvy n=121; DTG+F/TDF n=122) over four years from Asia (n=214, 88% Asian), Europe, and North and Latin America. Further results from the trial showed that participants who initiated treatment with Biktarvy had numerically higher hepatitis B surface antigen (HBsAg) loss (13% vs. 6%, p=0.059), HBeAg loss (26% vs. 14%, p=0.055), and alanine aminotransferase (ALT) normalization (73% vs 55%, p=0.066) (AASLD criteria). Safety findings were similar between the Biktarvy and DTF+F/TDF groups. Adverse events (AEs) included upper respiratory tract infection (17% vs. 11%), COVID-19 (13% vs. 11%), pyrexia (9% vs. 12%), ALT increase (7% vs. 11%), and nasopharyngitis (11% vs. 4%). ALT flares (elevations at ≥2 consecutive post-baseline visits) occurred in 11 participants (n=7: Biktarvy vs n=4: DTG+F/TDF). 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.

Gilead presented additional Biktarvy data at AIDS 2022. Five-year cumulative data demonstrated Biktarvy’s sustained efficacy and durable viral suppression as first-line therapy in people with HIV. No cases of treatment failure due to emergent resistance were detected in an analysis of five years of data from both studies, which further demonstrates the efficacy and tolerability profile of Biktarvy for the treatment of HIV in adults with no prior antiretroviral therapy history. Additionally, the results from the pooled analysis of Study 1489 and Study 1490 showed that 99% of participants who initiated treatment with Biktarvy and remained in the study for all 240 weeks achieved and maintained an undetectable viral load (HIV-1 RNA <50 copies/mL) through five years of follow-up (Week 240, 1489: n=208/213; 1490: n=218/219, missing equals excluded analysis). In addition to high rates of virologic suppression, participants achieved a median increase in CD4 count of 317 cells/μl from baseline at Week 240. The data support the long-term use of Biktarvy, with no significant changes to metabolic, bone, and renal markers.

“As we strive to optimize HIV treatment and advance scientific innovation, we’re committed to tailoring our research to address the individual needs of all people with HIV, including those with comorbidities,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “The HIV treatment research data presented at the 24^th International AIDS Conference are an important step in deepening our understanding of how to support the long-term and overall health of a broad range of people with HIV worldwide.”

The long-term data from Study 1489 and 1490 further reinforce Biktarvy’s safety profile. Across both studies, 10 participants (n=10/634) experienced a study-drug-related AE that led to drug discontinuation. The findings demonstrated minimal impact on bone mineral density (BMD) outcomes through five years. Mean percentage changes in hip and spine BMD through Week 240 in Biktarvy participants did not exceed -0.6%. Through five years, numerically small median changes in eGFR and stable TC:HDL ratios were observed in both studies. Among study participants, median change in weight from baseline through to Week 240 was +6.1kg. This finding is consistent with previously presented data. Initiation of therapy generally leads to weight gain in people with HIV who have no prior treatment history. Some of which is at least partially attributable to a return-to-health effect; however, weight gain is multifactorial in nature. Although it is often attributed to specific drugs, including TAF and integrase inhibitors, a growing body of evidence suggests that these drugs do not cause weight gain, but instead are “weight neutral”.

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 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.

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

About Studies 1489 and 1490

Study 1489 and Study 1490 are Phase 3, randomized, double-blind, active-controlled studies. For 144 weeks, treatment-naïve participants were blinded to receive either Biktarvy (n=634) or a dolutegravir-containing triple therapy (n=640). The primary endpoint was the proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm. Secondary endpoints included efficacy, safety, and tolerability assessed through Weeks 96 and 144. Beyond week 144, participants were able to receive Biktarvy in an active open-label extension phase for up to 96 weeks.

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 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 11 HIV medications, including the first single-tablet regimen to treat HIV and the first antiretroviral for pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV infection. These 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 impacted 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 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, 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 March 31, 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 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. All other trademarks are the property of their respective owner(s).

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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