Z Gastroenterol 2020; 58(01): e2-e3
DOI: 10.1055/s-0039-3402105
Lectures Session II Clinical Hepatology, Surgery, LTX: Friday, February 14, 2020, 3:25 pm – 4:10 pm, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Safety and Efficacy of 10 mg Myrcludex B/IFNa Combination Therapy in Patients with Chronic HBV/HDV Co-Infection

H Wedemeyer
1   University Hospital Essen, Department of Gastroenterology and Hepatology, Essen, Germany
,
K Schöneweis
2   MYR GmbH, Bad Homburg v.d.H., Germany
,
P Bogomolov
3   Clinical Institute M.F, Hepatology Department, Moscow, Russian Federation
,
N Vorokova
3   Clinical Institute M.F, Hepatology Department, Moscow, Russian Federation
,
V Chulanov
4   Central Research Institute of Epidemiology, Reference Center for Viral Hepatitis, Moscow, Germany
,
T Stepanova
5   Limited Liability Company 'Modern Medicine Clinic', Moscow, Germany
,
L Allweiss
6   University Medical Center Hamburg-Eppendorf, Department Internal Medicine, Hamburg-Eppendorf, Germany
7   German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel, Germany
,
M Dandri
6   University Medical Center Hamburg-Eppendorf, Department Internal Medicine, Hamburg-Eppendorf, Germany
7   German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel, Germany
,
S Ciesek
8   University Hospital Frankfurt, Frankfurt, Germany
,
U Dittmer
9   University Hospital Essen, Institute for Virology, Essen, Germany
,
W Haefeli
10   University Hospital Heidelberg, Clinical Pharmacology and Pharmacoepidemiology, Heidelberg, Germany
,
A Alexandrov
2   MYR GmbH, Bad Homburg v.d.H., Germany
,
S Urban
11   University Hospital Heidelberg, Department of Infectious Diseases, Heidelberg, Germany
12   German Center for Infection Research (DZIF), Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

Also available at
 

Background:

Myrcludex B/Bulevirtide (BLV) is a first-in-class entry inhibitor to treat HBV/HDV co-infected patients. BLV monotherapy, as well as combination with Tenofovir (TDF) or PEG-interferon α-2a (PEG-IFNα) induced serum and intrahepatic HDV RNA decline in two phase 2 clinical trials (MYR202/203). 2 mg and 5 mg BLV as combination therapy with PEG-IFNα showed strong synergistic effects on HDV RNA and induced HBsAg reduction. In a substantial number of patients HBsAg was undetectable and seroconversion occurred. We here present results of an extended 48 week phase 2 study (MYR203 extension) on HBV/HDV patients receiving 10 mg BLV in combination with PEG-IFNα or TDF.

Methods:

30 HBeAg-negative patients with chronic HBV/HDV co-infection were randomized in 2 arms. Over 48 weeks 10 mg BLV was subcutaneously injected once daily in combination with 180 µg PEG-IFNα once weekly or 5 mg BLV was administered twice daily (total daily dose of 10 mg BLV) with TDF. At baseline all patients were positive for HDV serum RNA with median viral loads of 6.28 log10 IU/ml in the 10 mg BLV/PEG-IFNα group and 6.24 log10 IU/ml in 10 mg BLV/TDF group. Robogene assay was employed to determine HDV RNA (LOD: 10 IU/ml).

Results:

Safety: Over 24 weeks BLV was well tolerated and no serious adverse event (SAE) was reported. Altogether 358 AEs were reported: two thirds were considered to be related to PEG-IFNα (n = 191) or TDF (n = 24). One third was considered to be related to BLV (mild n = 71, moderate n = 39, severe n = 11) and caused by total bile salt increase. Efficacy: Serum HDV RNA levels declined with median reductions from baseline by -4.84 log10 IU/ml in the BLV+PEG-IFNα arm (n = 15) and -2.80 log10 IU/ml in the BLV+TDF arm (n = 14) after 24 weeks. HDV RNA was undetectable in 60% and 21% patients, respectively. 20% of patients achieved ALT normalization by combination with IFN compared to 57% with TDF. HBsAg declined by > 1log10 IU/ml in two patients but was detectable further on.

Conclusion:

Over a period of 24 weeks 10 mg BLV in combination with PEG-IFNα or TDF is safe and well tolerated. The combined treatment with IFNa exhibits a strong synergistic effect on the antiviral response against HDV. Besides, administration of 5 mg BLV twice daily is not superior to 10 mg BLV once daily. End-of-treatment data (48 weeks) will be presented at the meeting.