In a Difficult-to-Treat Patient Population, Hepatitis D Therapy Could be Welcome Addition

Chronic HDV infection is the most severe form of viral hepatitis, with both a poor prognosis and high rates of mortality. And for those patients who have HDV and compensated cirrhosis with clinically significant portal hypertension (CSPH), they have very limited treatment options. Traditionally the only therapy available has been the off-label use of pegylated-interferon-a (PegIFNa), which has demonstrated limited therapeutic responses and an unfavorable safety profile.

However, a promising study using a newer HDV therapy, bulevirtide, has been able to demonstrate a clinical benefit for this patient population, according to investigators in Italy.

The investigators led by Pietro Lampertico, MD, PhD, studied the therapy and had impressive results in a small trial. Lampertico and his coinvestigators took 18 patients who had these characteristics and could not take interferon, and treated them with bulevirtide 2 mg over 48 weeks.

“We showed for the first time, the safety and efficacy of this drug,” Lampertico said. “We also showed that you could suppress delta viremia in these difficult-to-treat patients,” Lampertico said in an interview with Contagion.

Their study’s results were published in the Journal of Hepatology.

“A virological response was observed in 14 (78%) patients while a non-response was observed in 2 (11%). [alanine aminotransferase] (ALT) decreased to 35 (15- 86) U/L (p <0.001 vs. baseline), normalizing in 83% of patients. A combined response was observed in 67% of patients,” the investigators wrote.

In addition, the investigators reported, “HDV RNA declined by 3.1 (0.2-4.3) log IU/ml (p<0.001 vs. baseline), becoming undetectable in 5 patients (23%).”

Bulevirtide is an antiviral that binds and inactivates the sodium/bile acid cotransporter, blocking both HBV and HDV from entering hepatocytes. It was developed by Gilead, and back in 2020, it received conditional authorization from the European Medicines Agency, the medical agency that evaluates and supervises therapies for the continent. Bulevirtide is also up for FDA approval in the United States.

Lampertico acknowledged the significance of having a prospective HDV therapy with a very favorable safety profile for patients who had limited treatment options. “Up until a couple of years ago, the only option for these patients would have been liver transplantation…[in our study] all of the patients were on long-term [bulevirtide] monotherapy and none of the patients discontinued due to adverse events, and none of the patients had severe drug-related adverse events and this is really important for us and the patients.”

Contagion spoke to Lampertico who offered further insights on their work in this area, the mechanism of action for bulevirtide, and future plans for newer studies.