First treatment for chronic hepatitis D in adults, Hepcludex, approved in US
FDA uses accelerated pathway to OK Gilead's injection therapy for HDV infection
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The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Hepcludex (bulevirtide-gmod), in development by Gilead Sciences, for treating adults with chronic hepatitis D.
The treatment — the first approved in the U.S. for people with this hepatitis type — is indicated for chronic hepatitis D virus (HDV) infection in adults without cirrhosis, or irreversible liver scarring, or for those with compensated cirrhosis, which is where the liver can still function. It’s given as a once-daily 8.5 mg subcutaneous, or under-the-skin, injection.
“Today’s approval fills a critical gap in care for patients with chronic HDV infection, who until now have had no FDA-approved therapies available,” Wendy Carter, acting director of the office of infectious diseases in the FDA’s Center for Drug Evaluation and Research, said in an agency press release announcing the approval.
“For individuals living with this chronic viral infection, this new treatment option offers hope in managing a disease that can rapidly progress to serious liver complications,” Carter said.
The FDA’s accelerated approval pathway allows promising therapies to reach the market more quickly based on early clinical trial evidence suggesting effectiveness. Data from an international Phase 3 clinical trial, dubbed MYR301 (NCT03852719), showed that Hepcludex resulted in higher rates of a combined viral and biochemical response compared with delayed treatment.
Hepcludex’s full approval is dependent on additional clinical trial data confirming the treatment’s benefits in terms of disease-related clinical outcomes. Gilead has already started such a confirmatory trial, according to a company press release.
“The approval of Hepcludex represents a historic milestone for people living with HDV in the United States, marking the first FDA-approved treatment for HDV,” said Dietmar Berger, MD, PhD, chief medical officer at Gilead. “With Hepcludex, we now have the opportunity to deliver a meaningful clinical advancement that has the potential to change the trajectory of HDV for patients in the U.S.”
To support the newly authorized therapy, the Gilead Support Path Program offers information and resources, both for patients diagnosed with chronic hepatitis D and for healthcare professionals. Support Path aims to help patients better understand financial support options and insurance coverage, per the website.
In Canada, the European Union, and other countries, bulevirtide is also approved under the brand name Hepcludex, at a 2 mg dose, to treat people with chronic hepatitis D.
Hepcludex works to break the cycle of HVD infection
Hepatitis D is caused by HDV and can only occur in people already infected with the hepatitis B virus (HBV), which is a more widespread virus that’s responsible for hepatitis B. Chronic HDV is regarded as the most severe form of viral hepatitis, or liver inflammation, largely because it carries a substantially greater risk of rapid disease progression, liver failure, and death than HBV infection alone.
“Hepatitis delta virus is associated with rapid progression of liver disease and a high risk of serious or even life-threatening liver-related complications,” said Ira Jacobson, MD, at NYU Grossman School of Medicine in New York. “For patients, an [hepatitis D] diagnosis means managing two distinct viral liver diseases — hepatitis B and hepatitis D — each contributing to disease progression, monitoring demands, and treatment complexities.”
Hepcludex works by blocking the NTCP receptor protein on liver cells, through which the HBV and HDV dock and enter uninfected liver cells. Use of the therapy is expected to break the cycle of infection and slow the spread of the disease.
Its accelerated approval was supported mainly by data from the MYR301 study, which evaluated the effectiveness and safety of Hepcludex in 150 people, ages 18-65, with chronic hepatitis D.
Participants were randomly assigned to receive either one of two doses of Hepcludex (2 mg or 10 mg) once daily for nearly three years, or no antiviral therapy for the first year. Those in the so-called delayed treatment group then switched to the medication at 10 mg for nearly two years. All participants were also followed off-treatment for nearly two years.
The study’s main goal was to assess rates of a combined viral and biochemical response at one year: undetectable virus or a significant decline in viral load, plus normalization of blood aminotransferase, a liver damage marker.
Drop in viral load seen for over 70% at 3-year mark
The results showed that about half of the participants in the 2-mg (45%) and 10-mg (48%) immediate treatment groups achieved the combined response, compared with 2% of those in the delayed treatment group. The virus was undetectable in 12% of those in the 2-mg group and in 20% in the 10-mg group at one year, compared with none in the delayed treatment group.
After nearly three years, more than 70% in all three groups had experienced at least a significant drop in viral load. Further, 29% of those in the 2 mg group, 50% of those in the 10 mg group, and 52% of those in the delayed treatment group had no detectable virus. Among them, 36% remained virus-free for two years after discontinuing treatment.
The approval of Hepcludex for chronic HDV represents a critical advancement, introducing a long-awaited option that … has the potential to meaningfully alter the course of this devastating disease for people living with [hepatitis D] in the United States.
The most commonly reported adverse events with Hepcludex are allergic reactions, injection site reactions, headache, abdominal pain, fatigue, and itching. A boxed warning notes that discontinuing Hepcludex may trigger severe acute flares of both HDV and HBV infection.
The FDA had previously granted Hepcludex both breakthrough therapy and orphan drug status. These designations accelerate the development and review of promising treatments for rare diseases, qualifying sponsors for tax credits, fee waivers, and seven years of market exclusivity upon approval.
“The approval of Hepcludex for chronic HDV represents a critical advancement, introducing a long-awaited option that begins to address a significant unmet medical need and has the potential to meaningfully alter the course of this devastating disease for people living with [hepatitis D] in the United States,” Jacobson said.
