European Commission approves Vemlidy for chronic HBV

The European Commission issued marketing authorization for Vemlidy, a once-daily oral treatment for chronic hepatitis B virus infection in adults and adolescents, Gilead Sciences announced.

The marketing authorization extends to 28 countries in the European Union, Norway and Iceland, according to a press release.

Vemlidy (tenofovir alafenamide, Gilead Sciences; TAF) was also recently approved by the FDA for adults with chronic HBV infection with compensated liver disease, and in Japan for the suppression of viral replication in chronic HBV patients with evidence of HBV replication and abnormal liver function.

It is a nucleoside analog reverse transcriptase inhibitor and a prodrug of tenofovir that has demonstrated comparable efficacy at a dose less than one-tenth that of 245 mg Viread (tenofovir disoproxil fumarate, Gilead Sciences; TDF). Studies have shown the lower dose of TAF is made possible by its greater plasma stability and more efficient delivery of tenofovir to hepatocytes compared with TDF, and the lower exposure to tenofovir is associated with improved renal and bone laboratory safety parameters.

“As the first new treatment for chronic hepatitis B to be approved in Europe in nearly a decade, this approval marks a step forward in the management of a progressive, life-threatening disease affecting 13 million Europeans,” Pietro Lampertico, MD, PhD, head of the gastroenterology and hepatology division at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy, said in the press release. “Treating a lifelong disease such as chronic hepatitis B can present challenges as patients age, and the improvements in bone and renal laboratory safety parameters demonstrated by TAF compared to TDF allow it to provide an important new option for patients.”

The approval follows results from two 48-week international phase 3 studies involving 1,298 adults with chronic HBV infection. Study investigators randomly assigned 425 HBeAg-negative patients and 873 HBeAg-positive patients to receive TAF or TDF in each respective study, both of which met their primary noninferiority endpoints (the proportion of patients with plasma HBV DNA levels below 29 IU/mL at the end of the treatment period).

Patients who received TAF also achieved numerically higher rates of normalized blood serum alanine aminotransferase (ALT) levels, and both agents were well tolerated, with 1% adverse-event related discontinuations in the TAF group and 1.2% discontinuations in the TDF group.

Diarrhea, vomiting, nausea, abdominal pain, abdominal distension, flatulence, fatigue, headache, dizziness, rash, pruritis, increased ALT and arthralgia were the most common adverse events reported with TAF.

Viral suppression and biochemical responses were also maintained with continued TAF treatment through week 72, and changes in renal and bone laboratory safety parameters were better in the TAF groups at both weeks 48 and 72.

TAF has a boxed warning in its product label addressing the risks for lactic acidosis/severe hepatomegaly with steatosis and posttreatment severe acute exacerbation of HBV, according to the press release. It is not recommended for the treatment of HIV-1 infection as efficacy and safety have not been established in patients with HBV/HIV-1 coinfection.

“TAF reflects Gilead’s ongoing commitment to improve and simplify care for people with chronic infectious diseases, including hepatitis B, while we continue our research efforts for curative treatments,” Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, said in the press release. “We look forward to making TAF available as quickly as possible throughout the European Union.”

Disclosures: Bischofberger is employed by Gilead, and Lampertico reports financial relationships with Gilead.