Mirum puts Hepcludex in its sights with hep D readout

 Gilead Sciences' Hepcludex became the first drug to be FDA-approved for chronic hepatitis D virus (HDV) infections in May – but a potential rival from Mirum Pharma is already looming on the horizon.

Foster City, California-based Mirum has revealed topline results from the phase 3 AZURE-1 trial of brelovitug in chronic HDV, which show that the drug hit its primary objective, driving levels of the virus below the limit of detection and normalising levels of ALT, a biomarker for liver damage, at 24 weeks.

The data drop also includes 48-week data from the phase 2b portion of AZURE-1, which suggested the benefits on viral suppression and liver damage were maintained with longer follow-up. There was a 100% virologic response among patients treated for 48 weeks with brelovitug, which was dosed as a once-weekly or once-monthly subcutaneous injection in the trial.

HDV 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.

Brelovitug is an antibody that binds to hepatitis B surface antigen (HBsAg) on both HBV and HDV and is designed to neutralise and remove both viruses. It has a different mechanism of action from Hepcludex (bulevirtide), a viral entry inhibitor that is dosed by subcutaneous injection once a day and has been approved in Europe since 2020.

Before the Hepcludex approval, the only approved option for HBV/HDV patients in the US was a course of pegylated interferon alpha, which takes 48 weeks to complete and isn't very effective. A rival drug from Huahui Health, called libevitug, has been launched in China and targets the PreS1 protein on HBV and HDV.

The new data puts Mirum a little closer to its first marketing applications for brelovitug, and the company has said it is working towards an FDA filing in the first half of 2027, with a potential approval and launch in the latter half of the year.

There are around 15,000 US patients diagnosed with, and under care for, HBV/HDV co-infection, according to Mirum, which estimates that there could be a potential eligible patient population of 230,000 people in the US and Europe.

Topline data from two European-focused trials (AZURE-2 and AZURE-3), which are designed to support regulatory submissions specifically to the EMA, are due in the latter half of 2027.

The AZURE-1 readout is the second bit of positive news for Mirum in the space of two days, coming after the FDA greenlit its ALK2 inhibitor, Atebrioz (zilurgisertib), for the rare bone disease fibrodysplasia ossificans progressiva (FOP).

https://pharmaphorum.com/news/mirum-puts-hepcludex-its-sights-hep-d-readout