FDA gives bepirovirsen priority review for chronic hepatitis B
GSK expects a decision on the investigational therapy by Oct. 26
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The U.S. Food and Drug Administration (FDA) has accepted and placed under priority review an application seeking approval of bepirovirsen, GlaxoSmithKline (GSK)’s investigational therapy, for adults with chronic hepatitis B, the company announced.
Priority review shortens the review process to six months from the standard 10 months. A decision from the FDA is expected by Oct. 26.
The submission was supported by results from two Phase 3 clinical trials — B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) — which showed that a higher proportion of patients achieved a functional cure when bepirovirsen was added to standard-of-care medications, compared with standard treatment alone.
B-Well trials supported bepirovirsen application
A functional cure is defined as undetectable levels of hepatitis B virus DNA and hepatitis B surface antigen, or HBsAg, in the blood for at least 24 weeks after stopping all treatment, meaning the immune system can effectively control the infection without additional treatment.
Bepirovirsen is also under review in Europe as a treatment for chronic hepatitis B.
In its announcement, GSK also noted that bepirovirsen received FDA’s breakthrough therapy designation, a status for investigational therapies with preliminary clinical evidence suggesting they may offer substantial improvement over available treatments and that provides additional FDA guidance during development.
Bepirovirsen had previously received fast track designation from the FDA, another status meant to accelerate its development and review.
Chronic hepatitis B is a long-term liver infection that occurs when the immune system cannot effectively clear the hepatitis B virus. It affects more than 250 million people worldwide, including an estimated 1.7 million in the U.S. Hepatitis B is also a leading cause of liver cancer, accounting for approximately 56% of cases globally.
Standard treatment typically involves lifelong use of nucleos(t)ide analogues (NAs), a class of medications that stop the virus from replicating its DNA. But these antiviral therapies rarely lead to a functional cure, with rates as low as 1%, according to GSK. Achieving a functional cure, however, is associated with a significantly reduced risk of liver cancer and other serious complications.
Bepirovirsen targets hepatitis B genetic material
Bepirovirsen, developed in partnership with Ionis Pharmaceuticals, is designed to target and degrade hepatitis B virus genetic material, including messenger RNA (mRNA) and pregenomic RNA. This is intended to reduce viral replication and the production of viral proteins, potentially helping the immune system regain control of the infection. mRNA is an intermediate molecule derived from DNA that serves as a blueprint for protein production.
In the B-Well 1 and B-Well 2 trials, more than 1,800 adults with chronic hepatitis B from 29 countries were randomly assigned to receive either bepirovirsen or a placebo on top of their standard-of-care NAs. All had baseline HBsAg levels of 3,000 IU/mL or lower.
Top-line data from both trials showed that patients treated with bepirovirsen achieved significantly higher rates of functional cure compared with those on standard therapy alone, meeting the studies’ main goal.
Also, participants with lower initial levels of HBsAg, a viral surface protein used as a marker of chronic hepatitis B, were found to respond even more favorably than those with higher levels. The therapy showed an acceptable safety and tolerability profile consistent with previous studies.
While detailed results from the trials have not yet been disclosed, GSK plans to present these at the European Association for the Study of the Liver congress, being held May 27-30 in Barcelona, Spain, and virtually, and to submit them for publication in a peer-reviewed journal.
