番茄社区

VIENNA -- A first-in-class "entry inhibitor" for hepatitis D virus (HDV) infection suppressed viral RNA in most treated patients, phase II trial data reported here indicated, especially when combined with interferon.

Eight of 15 patients randomized to treatment with 2 mg of Myrcludex B (MyrB, also known as bulevirtide) in combination with pegylated interferon α 2a (PEG-IFNα) had undetectable HDV RNA, even 24 weeks after stopping treatment, reported Heiner Wedemeyer, MD, of Essen University Hospital in Germany.

At a press conference at the International Liver Conference, the annual meeting of the European Association for the Study of the Liver (EASL), moderator Markus Cornberg, MD, a member of the EASL Scientific Committee, and a researcher at Hannover Medical School in Germany, explained that HDV is a "neglected disease."

"We need to do something because we do not have good therapies for this besides interferon so far," he said.

Wedemeyer described HDV -- which only occurs simultaneously with hepatitis B -- as "the most severe form of chronic viral hepatitis." He further characterized various hepatitis infections to emphasize his point:

"[Hepatitis] E stands for emerging, C stands for 'mission completed' ... and D stands for devil," he said, adding that the virus is associated with a "higher likelihood to develop liver decompensation and also increase the likelihood of developing liver cancer."

There is no approved therapy for hepatitis D, but it is recognized by the FDA and European Medicines Agency (EMA) as an orphan disease, Wedemeyer noted.

, he said. Prior studies of the drug found that it induced HDV RNA declines and improved alanine aminotransferase (ALT) levels.

This study (MYR203) randomized 60 patients -- 15 to each of four regimens:

• PEG-IFNα only
• 2 mg MyrB + PEG-IFNα
• 5 mg MyrB + PEG-IFNα
• 2 mg MyrB only

Patients were treated for 48 weeks, followed by a 24 week follow-up period. MyrB was given once daily, and PEG-IFNα once weekly, both as subcutaneous injections. The study's primary endpoint was undetectable serum HDV RNA at week 72.

Treatment arms experienced a "continuous linear decline" of hepatitis D RNA, but patients then experienced a rebound in HDV RNA at the end of therapy, Wedemeyer said. But the "big surprise" in this trial was the combination arm with 2 mg of MyrB, which experienced a much smaller rebound than even the 5 mg MyrB combination arm or the MyrB monotherapy arm.

"Not only was there an additive response, but a profound decline of HDV RNA, and many cases stayed HDV RNA negative 24 weeks after the end of therapy," Wedemeyer said.

Secondary endpoints included a normalization of ALT levels, which was achieved in seven of 15 patients in the 2-mg MyrB combination arm and five of 15 in the 5-mg combination arm at week 72. Another secondary endpoint was a reduction of hepatitis B surface antigen (HBsAg), and indeed, six patients in the 2-mg combination arm experienced >1 log decline in HBsAg, and four patients had undetectable HBsAg at week 72.

Examining safety, there were no serious adverse events related to the study drug during the treatment period, and two serious adverse events not related to the study drug occurred during the follow-up period (anal fistula and proctitis). Wedemeyer noted an increase in bile salts in MyrB and PEG-IFNα-treated patients, though patients did not report any symptoms related to an increase in bile salts, and when the drug was stopped, it was "completely reversible," he said.

The majority of adverse events came from PEG-IFNα treatment, the authors noted, though Wedemeyer defended the safety of interferon therapy.

"Interferon may cause side effects, but we've been using it for 15 years in hepatology and it's current practice, so it's not special," he told 番茄社区.

Wedemeyer said the plan would be for a longer-term phase III study with MyrB monotherapy for patients with more severe disease, and combination therapy for those that could tolerate interferon.

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