Mirum Pharmaceuticals has secured a positive outcome for the first late-stage trial on its chronic hepatitis delta virus (HDV) therapy, brelovitug – potentially poising the drug for future regulatory submissions.
During the 48-week Phase IIb/III trial in question, which Mirum coined AZURE-1 (NCT06907290), treatment-naïve patients with HDV were randomised into three arms. The first two received a 300mg and 900mg weekly dose of brelovitug, respectively, while the third was put on a 24-week treatment delay, before beginning a 300mg weekly course of the experimental drug.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
With AZURE-1, researchers set out to determine how brelovitug could influence virologic response, as well as the levels of an enzyme called alanine transaminase (ALT), which leaks into the bloodstream when liver cells are damaged.
At the 24-week mark, 56% and 45% of the 300mg and 900mg treated patients experienced both a virologic response the normalisation of ALT levels – meeting the trial’s primary endpoint. In this case, researchers defined virologic response as a reduction of 2 log10 or more in HDV RNA from baseline, or undetectable levels of HDV RNA.
Meanwhile, 48-week data from the Phase IIb part of the AZURE-1 trial highlighted the drug’s durability of impact, with rates of viral suppression deepening, while the rates of ALT normalisation increased.
Patients also tolerated brelovitug well, with the most common side effect being injection site reactions and no treated individuals experiencing a serious adverse event (AE) at 24 weeks. No new safety signals were observed through to week 48.
Mirum eyes regulatory submissions for brelovitug
With a positive Phase IIb/III readout in the bag, Mirum is now looking ahead to data from the second late-stage HDV study on brelovitug, AZURE-4 (NCT07298330), which the company expects will read out in the final quarter of 2026. Along with AZURE-1, Mirum hopes that AZURE-4 will form a key part of its US Biologics License Application (BLA), which it expects to submit in the first half of 2027.
If all goes well with regulators, Mirum is also eyeing a market debut for brelovitug in Q4 2027, which would see the drug enter a market currently dominated by Gilead Sciences’ Hepcludex (bulevirtide-gmod) – a therapy that became the first to get the US regulatory greenlight for chronic HDV in May 2026.
At the time of Hepcludex’s approval, analysts at GlobalData, parent company of Clinical Trials Arena, noted that this development was a “significant milestone” for patients.
Mirum’s EVP of clinical development, Nancy Shulman, notes that there is now late-stage clinical evidence that brelovitug is a “well-tolerated, convenient, single agent” that can deliver deepening responses over time.
“Notably, these results were achieved in a broad patient population, including those with significant liver inflammation, cirrhosis and clinically significant portal hypertension,” she adds.
AZURE-1 investigator and GI and liver division chief at USC’s Keck School of Medicine, Norah Terrault, added that brelovitug demonstrating a combination of virologic response and ALT normalisation is an “encouraging” signal for a long term therapy, and that these results marked an important step forward for patients with HDV.
