• Hepatology Clinical Trials
• Liver Conditions
• Viral Infections

• Hepatology
• Hepatology Clinical Trials
• Liver Conditions
• Viral Infections

Chronic hepatitis B virus (HBV) infection is rarely cured with current therapies, and there is no effective therapy for hepatitis D virus (HBD) coinfection. Myrcludex B is a first-in-class entry inhibitor that inactivates the HBV and HDV receptor sodium taurocholate cotransporting polypeptide (NTCP). Myrcludex B specifically targets NTCP at the hepatocyte surface, inhibiting HBV and HDV receptor function and NTCP-mediated bile salt uptake into hepatocytes. Phase 1 clinical trials have demonstrated the safety of Myrcludex B.

The objective of the phase 2a study, presented by Stephan Urban, MD, University Hospital Heidelberg, Heidelberg, Germany, was to evaluate the safety, tolerability, and antiviral efficacy of Myrcludex B. The study included 2 cohorts. Cohort A consisted of 40 hepatitis B e antigen-negative patients with chronic HBV infection, HBV DNA > 2000 IU/mL, median HBV DNA 4.7 log₁₀ IU/ mL, and no cirrhosis. These patients were treated for 12 weeks with once-daily subcutaneous Myrcludex B at 0.5 mg, 1 mg, 2 mg, 5 mg, or 10 mg doses (n = 8/dosage group). Treatment was extended to 24 weeks for patients in the 10 mg group. Cohort B included 24 patients with HDV and compensated liver disease scheduled for 48 weeks of pegylated interferon-alpha (PEG-IFNα) therapy. Eight patients were pretreated with Myrcludex B 2 mg alone for 24 weeks (Cohort B1). Eight patients were treated with PEG-IFNα plus Myrcludex B for the first 24 weeks (Cohort B2), and the 8 remaining patients were treated with PEG-IFNα alone (Cohort B3). The end points for both cohorts were biochemical and virologic response, immunogenicity, bile salt elevations, pharmacokinetics, and safety and tolerability.

HBV DNA levels declined during Myrcludex B treatment in all groups. A pronounced effect of > 1 log₁₀ HBV reduction occurred in 6 patients in the 10 mg dose group and in 7 patients in the lower-dosing groups.

Myrcludex B had no significant effect on hepatitis B surface antigen (HBsAg) serum levels during treatment. At week 24, a > 1 log₁₀ HDV RNA reduction occurred in 6 Cohort B1 patients during Myrcludex B monotherapy and 7 Cohort B2 patients during combination therapy. HDV RNA became negative in 2 patients during Myrcludex B monotherapy and in 5 patients receiving combination therapy. Myrcludex B induced preS-specific antibodies in 4 patients during Myrcludex monotherapy and in 7 patients during combination therapy.

Treatment with Myrcludex B normalized alanine aminotransferase (ALT) levels in 55% of patients; median ALT levels declined from 76 U/L to 36 U/L at week 12 (P < .001). Myrcludex B had a dose-dependent effect on serum bile salt levels. Rapid elevation of taurocholic acid and glyocholic acid were observed with Myrcludex B > 1 mg/day. Myrcludex B withdrawal resulted in rapid bile salt normalization.

Adverse events included injection-site dermatitis (n = 3, 10 mg group) and psoriasis exacerbation leading to discontinuation (n = 1, Cohort B2).

The investigators concluded that Myrcludex B was safe and well tolerated in HBsAg-positive patients with or without HDV coinfection. HBV entry inhibition was associated with HBV DNA and strong HDV RNA declines and improved biochemical disease activity.

• © 2014 MD Conference Express®