FDA Approves Tenofovir Alafenamide for Adolescents With Chronic Hepatitis B Virus

The FDA has approved a supplemental new drug application for tenofovir alafenamide (Vemlidy; Gilead Science) for the treatment of chronic hepatitis B virus (HBV) infection in adolescents aged 12 years and older with compensated liver disease. Tenofovir alafenamide is a novel, targeted phosphonamidate prodrug of tenofovir that was initially approved by the FDA in 2016 for the once-daily treatment of adults with chronic HBV infection with compensated liver disease.

“While pediatric hepatitis B prevalence has dropped significantly in the US, children who develop chronic hepatitis B following an acute infection can experience lifelong health impact,” said Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, in a press release. “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.”

HBV is transmitted via bodily fluids from a person infected with the virus through sexual contact, by sharing syringes, or from mother to baby at birth. In some people, HBV is a short-term illness, whereas in others, it could become a long-term chronic infection, which is associated with their age at the time of infection. Approximately 90% of infants with HBV develop chronic infection compared with 2% to 6% of adults.

“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 Trial 1092 investigator Kathleen Schwarz, MD, pediatric gastroenterologist at Rady Children’s Hospital-San Diego, in a press release.

Tenofovir alafenamide is a nucleoside analog reverse transcriptase inhibitor specifically indicated to treat HBV with compensated liver disease. Because tenofovir does not readily cross cell membranes and is poorly absorbed, prodrugs of tenofovir are needed to increase its cellular permeability and oral bioavailability.

The approval for the new pediatric indication was based on 24-week data from Trial 1092, a phase 2 study that enrolled 70 patients between 12 and 18 years of age. The trial compared treatment with tenofovir alafenamide 25 mg vs placebo among 70 treatment-naïve and treatment-experienced patients aged 12 to less than 18 years of age and weighing at least 35 kg.

The study met the primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy. Overall, 21% of patients administered tenofovir alafenamide 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% of patients in the placebo cohort.

“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,” Schwarz in the release. “In the clinical trial, we saw that tenofovir alafendamide may represent an effective treatment option for people as young as 12 years of age living with chronic disease.”

The most common adverse events included headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia.

Warnings and precautions include risk of development of HIV-1 resistance in patients with HBV/HIV-1 coinfection, new onset or worsening renal impairment, and lactic acidosis and severe hepatomegaly with steatosis.

Reference

U.S. Food and Drug Administration Approves Vemlidy® (tenofovir alafenamide) for Treatment of Chronic Hepatitis B Virus Infection in Pediatric Patients. Gilead Sciences. News release. December 2, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/11/us-food-and-drug-administration-approves-vemlidy-tenofovir-alafenamide-for-treatment-of-chronic-hepatitis-b-virus-infection-in-pediatric-patients