Bepirovirsen under review in Europe as a treatment for chronic hepatitis B
Therapy outperformed standard care in promoting functional cure: Phase 3 trials
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The European Medicines Agency (EMA) has started its formal review of bepirovirsen, a move that could introduce a new class of therapy for adults with chronic hepatitis B.
Data from two Phase 3 trials suggest the treatment, developed by GlaxoSmithKline (GSK), is more effective than standard care at achieving a “functional cure,” a state where the immune system successfully controls the virus without the need for lifelong medication, according to a company press release.
The application was supported by the Phase 3 B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) clinical trials, which showed the investigational therapy was superior to a placebo in reducing viral markers to undetectable levels. Unlike current antivirals, which primarily suppress viral replication, bepirovirsen is designed to reduce viral proteins and stimulate the patient’s immune response.
GSK is developing bepirovirsen under a collaborative development and licensing agreement with Ionis Pharmaceuticals and plans to file for approval in other regions.
The global burden of hepatitis B
Hepatitis B is a viral infection that causes liver inflammation and is spread through contact with infected bodily fluids. While many infections are short-term, some people, particularly those infected early in life, develop a chronic infection that can increase the risk of liver cancer and liver failure.
GSK notes that chronic hepatitis B affects more than 250 million people worldwide, including 3.2 million in Europe, and accounts for approximately 56% of liver cancer cases globally.
Achieving a functional cure is associated with a significantly lower risk of liver cancer and other serious complications, making it a key goal in disease management. Standard-of-care treatment often requires lifelong use of oral nucleoside/nucleotide analogues (NAs), which work by preventing the virus from replicating its DNA. However, functional cure rates with these traditional therapies typically remain as low as 1%.
Bepirovirsen is an antisense oligonucleotide, or a short piece of lab-made genetic material, designed to target and destroy the virus’s messenger RNA (mRNA), an intermediary genetic molecule used as a template to produce viral proteins.
By removing this genetic template, the therapy suppresses the production of new viral proteins. Additionally, it is intended to stimulate the immune system to encourage a sustained, long-term defense against the infection.
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 bepirovirsen or a placebo in addition to their standard-of-care NAs. The primary goal was to determine if the add-on treatment increased functional cure rates, defined as undetectable levels of viral DNA and surface antigens for six months or longer after completing the regimen.
Both trials met this goal, showing significantly higher functional cure rates in the bepirovirsen group compared to standard therapy alone. Participants with lower baseline levels of the viral surface antigen (1,000 IU/mL or less) responded even more favorably. Bepirovirsen also demonstrated an acceptable safety and tolerability profile.
While specific data points have not yet been released, GSK expects to present complete trial results at a scientific congress and publish them in a peer-reviewed journal later this year.
Bepirovirsen has already been granted fast-track designation in the U.S., a status designed to accelerate the development and review of therapies that address significant unmet medical needs.
