FDA Expands Indication for Gilead's Vemlidy (Tenofovir Alafenamide) to Treat Chronic HBV Infection in Pediatric Patients as Young as Six

- Efficacy and Safety Profile of Once-Daily Vemlidy Demonstrated in Children Six Years of Age (Weighing at Least 25kg) 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 six years of age and older and weighing at least 25 kg with compensated liver disease.

Vemlidy is a targeted prodrug of tenofovir that was approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. In 2022, the FDA approved Vemlidy for the treatment of chronic HBV infection in pediatric patients 12 years of age and older with compensated liver disease. Vemlidy is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines.

"Chronic hepatitis B can have a significant and lasting impact on the health of children. If left untreated, hepatitis B can lead to liver cirrhosis and liver cancer," said Chaun-Hao Lin, MD, Associate Professor of Clinical Pediatrics Krek School of Medicine of USC. "As a clinician, I am well aware of the critical importance of promptly treating this disease to avoid possible complications and liver damage. The clinical trial demonstrated that tenofovir alafenamide may represent an effective treatment option for children as young as six years old affected by this chronic disease."

Vemlidy's approval in this pediatric patient population is supported by Week 96 data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 18 treatment-naïve and treatment-experienced patients aged 6 to less than 12 years weighing at least 25 kg (Cohort 2, Group 1). Participants in the Vemlidy group and in the placebo group who switched to open-label Vemlidy after Week 24 demonstrated progressive increases in the rates of virological suppression through Week 96 overall and within both study cohorts (children and adolescents).

"The expanded indication for Vemlidy for the treatment of children as young as six years old is a testament to the safety, tolerability and efficacy profile of this therapy," said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. "Effective and tolerable options for children require our best science and a dedicated focus. The work of our Gilead Pediatric Center of Excellence is responsible for coordinating pediatric clinical trials for treatments for cancer, HIV, hepatitis B, and COVID-19 and we will continue our research to help address unmet treatment needs for children."

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 events in the week 96 pediatric population reported in ≥5% were: nasopharyngitis, headache, COVID-19, pyrexia, diarrhea, upper respiratory tract infection, cough, respiratory tract infection viral, abdominal pain upper. Overall, abdominal pain upper and metabolic nephropathy were the only study drug-related adverse events, which occurred in > 1 participant, reported in 2.3% (2/88 participants) each.

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.
• Coadministration of VEMLIDY with carbamazepine, the tenofovir alafenamide dose should be increased to two tablets once daily.

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 six years of age and older and weighing at least 25 kg with compensated liver disease.

About the 1092 Study

Study 1092 is an ongoing Phase 2 clinical trial that randomized 88 treatment-naïve and treatment-experienced patients with chronic hepatitis B infection 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) and 6 to less than 12 years weighing at least 25 kg to receive either Vemlidy 25 mg (N = 12) or placebo (N=6) 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, 19% (11/59) of patients treated with Vemlidy 25 mg achieved HBV DNA < 20 IU/mL at Week 24 compared to 0% (0/23) of patients treated with placebo. The overall percentage of patients with HBV DNA < 20 IU/mL progressively increased in the Vemlidy 25 mg group relative to the Week 24 time point at both Week 48 (37% [22/59 subjects]) and Week 96 (61.0% [36/59 subjects]).

The overall median change from baseline in ALT values for the Vemlidy and placebo-Vemlidy treatment groups, respectively, was -39.5 U/L and -46.5 U/L at Week 96. At 96 weeks, ALT normalization (AASLD criteria) was achieved for 54% of Vemlidy-treated patients and 57% of patients who switched from placebo to Vemlidy. 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 similar for Vemlidy-treated patients and placebo-treated patients (1.6% (N=48) and 1.9% (N=23) for lumbar spine, and 1.9% (N=50) and 2.0% (N=23) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were 0.01 and -0.07 for the lumbar spine, and -0.04 and -0.04 for whole body, for 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, COVID-19 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 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 Vemlidy; the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV in pediatric patients; and any assumptions underlying any of the foregoing. 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 Annual Report on Form 10-K for the year ended December 31, 2023, 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.

Source: Gilead Sciences, Inc.

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