Background & Aims
The therapeutic option for patients chronically infected with hepatitis delta virus (CHD) is limited to interferon alpha with rare curative outcome. Myrcludex B is a first-in-class entry inhibitor inactivating the hepatitis B and D receptor sodium taurocholate co-transporting polypeptide. We report the interim results of a pilot trial on chronically infected HDV patients treated with myrcludex B, or pegylated interferon alpha (pegIFNα-2a) or their combination.
24 patients with CHD infection were equally randomized (1:1:1) to receive myrcludex B, or pegIFNα-2a or their combination. Patients were evaluated for virological and biochemical response and tolerability of the study drugs at weeks 12 and 24.
Myrcludex B was well tolerated and no serious adverse event occurred. Although hepatitis B surface antigen levels remained unchanged, HDV RNA significantly declined at week 24 in all cohorts. HDV RNA became negative in two patients each in the Myr and IFN cohort, and in five patients of the Myr-IFN cohort. ALT decreased significantly in the Myr cohort (six of eight patients), and HBV DNA was significantly reduced at week 24 in the Myr-IFN cohort. Virus kinetic modeling suggested a strong synergistic effect of myrcludex B and pegIFNα-2a on both HDV and HBV.
Myrcludex B showed a strong effect on HDV RNA serum levels and induced ALT normalization under monotherapy. Synergistic antiviral effects on HDV RNA and HBV DNA in the Myr-IFN cohort indicated a benefit of the combination of entry inhibition with pegIFNα-2a to treat CHD patients.
Myrcludex B is a new drug to treat hepatitis B and D. After 24 weeks of treatment with myrcludex B and/or Interferonα-2a, HDV RNA, a relevant marker for hepatitis D infection, decreased in all patients with chronic hepatitis B and D. Two of eight patients which received either myrcludex B or Interferonα-2a, became negative for HDV RNA, and five of seven patients who received both drugs at the same time became negative. The drug was well tolerated.