In the Journals

Myrcludex B led to decline of HDV RNA serum levels in 1b/2a study

Myrcludex B led to a decline of hepatitis D RNA serum levels in patients with chronic hepatitis D, according to phase 1b/2a study results published in the Journal of Hepatology.

“Our study demonstrated for the first time the clinical ‘proof of concept’ of entry inhibition for chronic hepatitis D patients, as monotherapy myrcludex B was very well-tolerated,” Pavel Bogomolov, at the Moscow Regional Research Clinical Institute, and colleagues wrote. “The antiviral effect of myrcludex B was more pronounced in the combination with [pegylated interferon alpha (PEG-IFN a-2a)] indicating that a combination of both drugs is promising for future clinical trials.”

For patients with chronic hepatitis D, the only available treatment is interferon alpha. The novel therapy myrcludex B is a first-in-class entry inhibitor that works by inactivating the hepatitis B virus and hepatitis D virus receptor sodium taurocholate co-transporting polypeptide.

Bogomolov and colleagues performed a pilot trial on 24 patients chronically infected with HDV and treated with myrcludex B, PEG-IFN a-2a or both. The researchers evaluated the patients for response and tolerability at weeks 12 and 24.

They found that myrcludex B was well-tolerated and that there were no serious adverse events. Although hepatitis B surface antigen levels remained the same, HDV serum RNA levels declined in the combination group and alanine aminotransferase levels declined in the myrcludex B monotherapy group. Virus kinetic modelling suggested a strong synergistic effect of myrcludex B and PEG-IFN a-2a on both HDV and HBV.

Although the primary objective of the study — observed change in HBsAg levels — failed, Bogomolov and colleagues reached an important objective of reducing HDV RNA levels, Mario Rizzetto, in the department of internal medicine and gastroenterology at the University of Torino in Italy, and Grazia Anna Niro, in the gastroenterology unit at IRCCS Hospital, wrote in an accompanying editorial.

“The critical issue is whether the decline of HDV-RNA obtained with [myrcludex b] will be of long-term clinical relevance in the absence of an impact on the HBsAg,” Rizzetto and Niro wrote. “Though the lack of an impact on the HBsAg does not bode well for [myrcludex b], it will be interesting to see whether inhibition of HDV-RNA is maintained or further enhanced in the second, [myrcludex b]-free part of the study, through a potentially direct effect on HDV-RNA.” – by Will Offit

Disclosure: Bogomolov, Rizzetto and Niro report no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Myrcludex B led to a decline of hepatitis D RNA serum levels in patients with chronic hepatitis D, according to phase 1b/2a study results published in the Journal of Hepatology.

“Our study demonstrated for the first time the clinical ‘proof of concept’ of entry inhibition for chronic hepatitis D patients, as monotherapy myrcludex B was very well-tolerated,” Pavel Bogomolov, at the Moscow Regional Research Clinical Institute, and colleagues wrote. “The antiviral effect of myrcludex B was more pronounced in the combination with [pegylated interferon alpha (PEG-IFN a-2a)] indicating that a combination of both drugs is promising for future clinical trials.”

For patients with chronic hepatitis D, the only available treatment is interferon alpha. The novel therapy myrcludex B is a first-in-class entry inhibitor that works by inactivating the hepatitis B virus and hepatitis D virus receptor sodium taurocholate co-transporting polypeptide.

Bogomolov and colleagues performed a pilot trial on 24 patients chronically infected with HDV and treated with myrcludex B, PEG-IFN a-2a or both. The researchers evaluated the patients for response and tolerability at weeks 12 and 24.

They found that myrcludex B was well-tolerated and that there were no serious adverse events. Although hepatitis B surface antigen levels remained the same, HDV serum RNA levels declined in the combination group and alanine aminotransferase levels declined in the myrcludex B monotherapy group. Virus kinetic modelling suggested a strong synergistic effect of myrcludex B and PEG-IFN a-2a on both HDV and HBV.

Although the primary objective of the study — observed change in HBsAg levels — failed, Bogomolov and colleagues reached an important objective of reducing HDV RNA levels, Mario Rizzetto, in the department of internal medicine and gastroenterology at the University of Torino in Italy, and Grazia Anna Niro, in the gastroenterology unit at IRCCS Hospital, wrote in an accompanying editorial.

“The critical issue is whether the decline of HDV-RNA obtained with [myrcludex b] will be of long-term clinical relevance in the absence of an impact on the HBsAg,” Rizzetto and Niro wrote. “Though the lack of an impact on the HBsAg does not bode well for [myrcludex b], it will be interesting to see whether inhibition of HDV-RNA is maintained or further enhanced in the second, [myrcludex b]-free part of the study, through a potentially direct effect on HDV-RNA.” – by Will Offit

Disclosure: Bogomolov, Rizzetto and Niro report no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.