Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study.

BACKGROUND & AIMS: The therapeutic option for patients with chronic hepatitis delta virus infection (CHD) is limited to interferon alpha with rare curative outcome. Myrcludex B is a first-in-class entry inhibitor inactivating the hepatitis B virus (HBV) and hepatitis D virus (HDV) 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.

METHODS

Twenty-four 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.

RESULTS

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 Myrcludex B and PegIFNα-2a cohorts, and in five patients of the Myrcludex B+PegIFNα-2a cohort. ALT decreased significantly in the Myrcludex B cohort (six of eight patients), and HBV DNA was significantly reduced at week 24 in the Myrcludex B+PegIFNα-2a cohort. Virus kinetic modeling suggested a strong synergistic effect of myrcludex B and PegIFNα-2a on both HDV and HBV.

CONCLUSIONS

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.

LAY SUMMARY: Myrcludex B is a new drug to treat hepatitis B and D infection. After 24weeks of treatment with myrcludex B and/or pegylated interferon α-2a, HDV R NA, 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 pegylated interferon α-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.