Gilead claims first FDA nod for a hepatitis D therapy

At its second attempt, Gilead Sciences has won FDA approval for chronic hepatitis D virus (HDV) therapy Hepcludex, almost four years after it got the go-ahead in Europe.

The accelerated approval makes viral entry inhibitor Hepcludex (bulevirtide) the first HDV therapy cleared in the US, with the FDA backing the use of the drug in adults without cirrhosis or with compensated cirrhosis, where the liver is scarred but still retains quite a lot of its function.

In 2022, the FDA turned down Gilead's first application for Hepcludex, saying it had concerns about the "manufacture and delivery" of the drug but did not need any additional efficacy or safety data.

That led to speculation that the delay to the programme would be fairly short, but as it turned out, resolving the what turned out to be complex manufacturing and supply-chain logistics concerns took years to resolve.

HDV is unusual in that it exists only as a co-infection with hepatitis B virus (HBV) and occurs in around 5% of the estimated 254 million people around the world who are chronically infected with HBV – almost 13 million people. Co-infection is serious, however, as having both HBV and HDV increases the risk of progression, liver disease-related death, and liver cancer, and there are estimated to be between 40,000 and 80,000 co-infected patients in the US alone.

Before the Hepcludex approval, the only approved option for HBV/HDV patients was a course of pegylated interferon alpha, which takes 48 weeks to complete and isn't very effective.

In China – which has a high number of hepatitis cases, a rival entry inhibitor from Huahui Health called libevitug was cleared by the National Medical Products Administration (NMPA) earlier this year.

"For patients, an HDV diagnosis means managing two distinct viral liver diseases…each contributing to disease progression, monitoring demands, and treatment complexities," said Dr Ira Jacobson, a hepatitis specialist at NYU Grossman School of Medicine in the US.

In the pivotal MYR301 study, treatment with Hepcludex led to significant HDV RNA declines and improvements in liver damage biomarkers at 48 weeks, with 48% of patients classed as responders at that timepoint.

"The approval of Hepcludex for chronic HDV represents a critical advancement, introducing a long-awaited option that begins to address a significant unmet medical need and has the potential to meaningfully alter the course of this devastating disease for people living with HDV in the US," said Jacobson.

Gilead doesn't break out sales of Hepcludex specifically, but in its fourth-quarter results said that combined sales of all its liver disease therapies – which include treatments for HBV and HDV as well as Livdelzi (seladelpar) for primary biliary cholangitis (PBC), grew 6% to $3.2 billion in full-year 2025.