Investigational bulevirtide (Hepcludex) was effective and well tolerated in patients with chronic hepatitis delta virus (HDV), a researcher reported.
In an interim analysis of the ongoing phase III MYR301 study, the proportion of people with HDV achieving the combined virological and biochemical response was 36.7% with bulevirtide 2 mg, 28% in participants receiving bulevirtide 10 mg, and 0% in participants currently under observation who have not received antiviral treatment to date, reported Heiner Wedemeyer, MD, of Hannover Medical Hospital in Germany.
Treatment for 24 weeks with bulevirtide 2 mg or 10 mg had a superior response (P<0.001) to the no treatment group, with bulevirtide 2 mg for 24 weeks having a numerically higher response rate compared with bulevirtide 10 mg. Also, rapid alanine aminotransferase reduction and normalization was seen in >50% of patients in the bulevirtide 2-mg group versus the 10-mg group or no treatment groups, Wedemeyer reported in a presentation at the European Association for the Study of the Liver (EASL) virtual meeting.
Bulevirtide monotherapy at 24 weeks demonstrated no serious adverse events (AEs), no symptomatic elevations in bile salts, or AEs leading to discontinuation related to the study drug.
“Hepatitis D virus is the most severe form of viral hepatitis, and occurs only as a coinfection in individuals who have hepatitis B virus [HBV],” Wedemeyer explained, adding that at least 12 million people worldwide are likely experiencing HBV-HDV coinfection.
“Until now, people with HDV have had very limited treatment options and a poor prognosis,” he noted.
Bulevirtide is “a peptide derived from the [HBV] surface antigen [that is] slightly modified, and which you can inject in patients,” Wedemeyer explained. It is a first-in-class entry inhibitor for the treatment of chronic HDV, and a 2-mg dose has conditional marketing authorization in the E.U. The agent will most likely be submitted to the FDA later in 2021, according to Wedemeyer.
He highlighted the fact that bulevirtide therapy was tied to a rapid reduction in liver enzymes. “We are talking…about a very severe liver disease,” he said. The “‘D’ stands for ‘devil’… causing a high risk to develop liver cancer and cirrhosis. For many years, we only used pegylated interferon, which helps roughly one-quarter to one-third of patients.”
In another study, the phase IIb MYR204 trial, 175 people with chronic HDV were randomly allocated to four treatment arms groups: peginterferon alfa-2a; bulevirtide 2 mg plus peginterferon alfa-2a; bulevirtide 10 mg plus peginterferon alfa-2a; and bulevirtide 10 mg. In that study, the proportion of participants who achieved a combined response after 24 weeks of treatment was higher in those treated with bulevirtide, with the highest response rate seen in the monotherapy group. Treatment with bulevirtide, both as monotherapy or in combination with peginterferon alfa-2a, was well-tolerated, with mostly mild or moderate AEs and no reported serious AEs or AEs leading to discontinuation of bulevirtide, according to another EASL presentation.
EASL press conference Tobias Böttler, MD, of the Universitätsklinikum Freiberg in Germany, commented that bulevirtide “is the best drug we have today to treat this disease,” but he cautioned that “We do need more data on how long to treat. We might need combination therapies in the future…but we’re really in a desperate situation when we’re looking at treatment of patients with hepatitis delta with active disease.”
MYR301 and MYR204 were supported by Gilead.
Wedemeyer disclosed relationships with Bristol-Myers Squibb, Roche, Gilead, and Idenix.
Böttler disclosed no relationships with industry.