FDA Approves Tenofovir Alafenamide for Chronic Hepatitis B Virus in Pediatric Patients

The FDA has approved a supplemental new drug application for tenofovir alafenamide (Vemlidy; Gilead) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in patients 12 years of age and older with compensated liver disease. Tenofovir alafenamide 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.

“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,” clinical trial investigator Kathleen Schwarz, MD, a pediatric gastroenterologist at Rady Children’s Hospital-San Diego, said in a press release. “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.”

HBV is transmitted in bodily fluids from an infected person via sexual contact, sharing syringes, or from a mother to her baby at birth. In some patients with HBV, the virus is a short-term illness, whereas in other patients, HBV may be a long-term chronic infection. Approximately 90% of infants with HBV will develop chronic infection vs 2% to 6% of adults.

Tenofovir alafenamide is a nucleoside analog reverse transcriptase inhibitor specifically indicated to treat HBV in adults with compensated liver disease. The medication is a novel, targeted phosphonamidate prodrug of tenofovir. Because tenofovir does not readily cross cell membranes and is poorly absorbed, prodrugs of tenofovir are necessary to improve its cellular permeability and oral bioavailability.

Tenofovir alafenamide is recommended by guidelines from the American Association for the Study of Liver Diseases and European Association for the Study of the Liver as a preferred or first-line treatment for adult patients with chronic HBV with compensated liver disease in guidelines from the American Association for the Study of Liver Diseases and European Association for the Study of the Liver.

The latest approval was based on 24-week data from a phase 2 clinical trial (Trial 1092), which randomized 70 treatment-naïve and treatment-experienced patients between 12 and 18 years of age who weigh at least 35 kg to receive either tenofovir alafenamide 25 mg (N=47) or placebo (N=23).

The study achieved the primary endpoint of percentage of patients with HBV DNA levels less than 20 IU/mL at 24 weeks of therapy. The results showed that overall, 21% (10/47) of patients administered tenofovir alafenamide 25 mg achieved HBV DNA <20 IU/mL at 24 weeks vs 0% (0/23) of subjects administered placebo.

“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, 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.”

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. Published November 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. Accessed November 2, 2022.