Gilead Submits BLA for Bulevirtide, a Potential First-in-Class Therapy for Chronic Hepatitis Delta

On November 19, 2021, Gilead Sciences announced that it had submitted a Biologics License Application (BLA) for bulevirtide to the U.S. FDA. This is a potential "first-in-class" hepatitis therapy for the treatment of adult patients with chronic hepatitis delta virus (HDV) infection accompanied by compensated disease. Previously, bulevirtide had received breakthrough therapy designation and orphan drug status from the FDA for the treatment of hepatitis D. The press release noted that, if approved, it would become the first FDA-approved therapy for adult patients with chronic HDV infection accompanied by compensated disease.

Hepatitis D is the most severe type of viral hepatitis, with a 5-year mortality rate as high as 50% for patients who develop cirrhosis. Generally speaking, HDV only infects patients with hepatitis B. Under the influence of these two viruses, liver damage progresses more rapidly, leading to faster onset of liver fibrosis, cirrhosis, and hepatic decompensation, with higher risks of developing liver cancer and death. Bulevirtide can bind to the NTCP receptor on the surface of liver cells, thereby inhibiting HDV and hepatitis B virus (HBV) from entering liver cells and also suppressing viral spread within the liver.

The submission of this BLA is based on positive data obtained from a Phase 2 clinical trial and an ongoing Phase 3 clinical trial. In the Phase 3 clinical trial, 150 patients with chronic hepatitis D were randomly assigned to receive either 2 mg bulevirtide (n=49) or 10 mg bulevirtide (n=50) once daily; or no antiviral treatment (control group, n=51).

The interim results of the trial showed that, after 24 weeks of treatment, the proportion of patients achieving a combined virological and biochemical response was 36.7% in the 2 mg bulevirtide group (p<0.001), 28% in the 10 mg bulevirtide group, and 0% in the control group. Additionally, more than 50% of patients in the 2 mg bulevirtide group experienced a rapid reduction and normalization of serum alanine aminotransferase (ALT) compared to only 5.9% in the control group.

The safety profile of the drug was consistent with previous studies, with no serious adverse events (AEs) reported. The most common AEs related to bulevirtide treatment were increased bile salt levels in the blood, injection site reactions, and worsening of liver disease after discontinuation of bulevirtide.

"Our goal is to provide safe and effective treatments for people with the most severe form of chronic viral hepatitis, a condition that can rapidly progress to serious complications including fibrosis, cirrhosis, and liver cancer, and increase the risk of death," commented Dr. Merdad Parsey, Chief Medical Officer of Gilead Sciences. "We look forward to working with the FDA with the aim of bringing this innovative therapy to patients with hepatitis D as soon as possible."

References:

[1] Gilead Submits Biologics License Application to U.S. Food and Drug Administration for Bulevirtide, an Investigational Treatment for People Living With Chronic Hepatitis Delta. Retrieved November 19, 2021, from https://www.businesswire.com/news/home/20211119005269/en

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