Committee for European Medicines Agency Recommends Hepatitis D Therapy

Late last week, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) offered a favorable opinion on the use of bulevirtide for adult patients living with hepatitis D (HDV) and compensated liver disease.

The CHMP’s opinion was based from data of the phase 3 MYR301 study demonstrating the efficacy and safety of bulevirtide, resulting in the removal of the specific obligation related to the conditional marketing authorization.

Bulevirtide is a first-in-class investigational antiviral that binds and inactivates the sodium/bile acid cotransporter, blocking both HBV and HDV from entering hepatocytes. The therapy was developed by Gilead and was granted Breakthrough Therapy and Orphan Drug designations by the FDA.

HDV is the most severe form of viral hepatitis and affects an estimated 5% of people living with hepatitis B (HBV). The disease's prevalence is over 12 million people globally. For HDV patients with advanced disease progression, including cirrhosis, mortality rates can be as high as 50% within five years.

Watch this interview with an investigator who studied bulevirtide and had impressive results in a small trial.

“People living with HDV have had very limited treatment options and without treatment, they often rapidly progress to severe liver disease or liver cancer,” Heiner Wedemeyer, MD, director, Clinic for Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, said in a statement.
“Until bulevirtide, we have not had any approved options to treat these patients, but we now have a treatment conditionally approved specifically for HDV with a positive recommendation for full approval.”

What the Data Demonstrated
Investigators conducted phase 2 and phase 3 studies of bulevirtide studying its 48-week safety and efficacy in patients with chronic HDV.

In the first study, 269 patients were either treated with bulevirtide alone at 2 mg daily (64 patients) or 10 mg daily (115 patients), while 39 patients received Peg-IFNα, and 51 patients served as controls. After 48 weeks, overall incidence of participants who experienced adverse events was similar between the 2 groups that received bulevirtide (85 and 86 percent) compared to 89 percent in the Peg-IFNα group and 76 percent in the control group.

The study authors noted most adverse events were mild or moderate, and they wrote that bulevirtide 2 mg daily was safe and well-tolerated, including in patients with compensated cirrhosis as well as among patients who were not naïve to interferon.

Last fall, the FDA sent Gilead a Complete Response Letter on bulevirtide. In the letter, the federal agency said it had concerns about the manufacture and delivery of the therapy.

“While we are disappointed with this outcome, we remain confident in the benefits bulevirtide could potentially bring to people living with HDV in the US. Today’s news does not change the safety and efficacy profile observed in clinical trials to date,” Gilead Chief Medical Officer Merdad Parsey, MD, PhD, said in a statement at the time. “We look forward to continuing our active discussions with FDA so that we may bring bulevirtide to people living with HDV in the US as soon as possible.”

It is important to note that FDA did not ask Gilead for further studies for bulevirtide, and it is expected that bulevirtide will be back in front of the FDA again as the company will seek full federal approval in the US.

Next Steps
The European Commission (EC) will review the CHMP recommendation, and if adopted, bulevirtide will be fully authorized in the European Union.