U.S. Food and Drug Administration Approves Vemlidy® (tenofovir alafenamide) for Treatment of Chronic Hepatitis B Virus Infection in Pediatric Patients

– Approval Expands on Previous FDA Approval of Vemlidy in Adults Living With This Chronic Liver Disease –

–Efficacy and Safety of Once-Daily Vemlidy Demonstrated in Individuals 12 Years of Age and Older –

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Vemlidy^® (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients 12 years of age and older with compensated liver disease.

Vemlidy is a novel, targeted prodrug of tenofovir that was previously approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. It is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease in guidelines from the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).^1,2

Vemlidy’s approval in this pediatric patient population is supported by 24-week data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 70 treatment-naïve and treatment-experienced patients aged 12 to less than 18 years weighing at least 35 kg. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 21% (10/47) of subjects treated with Vemlidy 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% (0/23) of subjects treated with placebo.

“Chronic hepatitis B can have a significant long-term health impact on children, including the development of liver cancer later in life if the disease is left untreated, which is compounded by treatment challenges in this population,” said Kathleen Schwarz, MD, Pediatric Gastroenterologist, Rady Children’s Hospital-San Diego, an investigator in the Vemlidy clinical trial. “As a clinician, I recognize the critical importance of treating this disease as quickly as possible to help avoid complications and potential damage to the liver. In the clinical trial, we saw that tenofovir alafenamide may represent an effective treatment option for people as young as 12 years of age living with this chronic disease.”

“While pediatric hepatitis B prevalence has dropped significantly in the U.S., children who develop chronic hepatitis B following an acute infection can experience lifelong health impact,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “Gilead is focused on meeting the biggest challenges in liver disease and impacting the course of disease. With an established safety profile and once-daily dosing, Vemlidy provides physicians a new option to address the treatment needs of pediatric patients living with hepatitis B.”

Vemlidy has a boxed warning in its product label regarding post-treatment severe acute exacerbation of hepatitis B. See below for important safety information.

U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE OF VEMLIDY

BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B

Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Warnings and Precautions

Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
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 TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY 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 all clinical studies through Week 144 were headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia.

Drug Interactions

Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption.

Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.

Dosage and Administration

Testing Prior to Initiation: HIV infection.
Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.
Dosage: 1 tablet taken once daily with food.
Renal Impairment: Not recommended in patients with end stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment.
Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.

Indication

VEMLIDY is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 12 years of age and older with compensated liver disease.

About the 1092 Study

Trial 1092 was a Phase 2 clinical trial that randomized 70 treatment-naïve and treatment-experienced patients between the ages of 12 to less than 18 years weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or placebo (N=23) once daily. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 21% (10/47) of subjects treated with Vemlidy 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% (0/23) of subjects treated with placebo. Investigators also observed higher rates of serum alanine aminotransferase (ALT) normalization based on AASLD criteria at 24 weeks; 44% of Vemlidy-treated patients and 0% of placebo-treated patients achieved ALT normalization, with median (Q1, Q3) changes from baseline in ALT of -32.0 U/L (-63.0, -13.0 U/L) and 1.0 U/L (-10.0, 25.0 U/mL). Serum ALT is an enzyme used to monitor liver damage. Importantly, the mean percent changes in bone mineral density from baseline to Week 24 were numerically similar for Vemlidy- treated patients and placebo-treated patients (2.4% (N=37) and 1.9% (N=18) for lumbar spine, and 1.5% (N=39) and 1.9% (N=18) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were -0.03 and -0.09 for lumbar spine, and -0.05 and -0.01 for whole body, for the Cohort 1 VEMLIDY and placebo groups, respectively.

About Hepatitis B

Hepatitis B (HBV) is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer and death in up to a third of patients. Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use or perinatally from mother to child. Early symptoms may include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives) and joint pain. The disease is often asymptomatic which may lead to undiagnosed individuals. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes) and right-sided abdominal pain (especially with external pressure or palpitation).

About Gilead Sciences in Liver Disease

For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care.

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. 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 the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV and the possibility of unfavorable results from ongoing and additional clinical studies involving Vemlidy. 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. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, as filed with the U.S. Securities and Exchange Commission. 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 statement.

U.S. Prescribing Information for Vemlidy, including BOXED WARNINGS, is available at www.gilead.com

Vemlidy, 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 (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

¹ Terrault NA, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. ² European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021.

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Jacquie Ross, Investors investor_relations@gilead.com

Jeff Eggert, Media jeff.eggert1@gilead.com

Source: Gilead Sciences, Inc.