Novel drug safe, efficacious in patients with HDV-related advanced liver disease

Treatment with REP 2139-Mg (REP), a nucleic acid polymer, demonstrates efficacy and an acceptable safety profile among patients with hepatitis D virus (HDV) and advanced chronic liver disease (CLD), reports a recent study.

“REP may induce sustained virological response of HDV and functional cure of HBV, independent of PegIFN co-administration,” the investigators said. “Clinical improvement may also occur in patients with decompensated cirrhosis.”

Thirty-three patients with HDV-related advanced CLD aged 21‒69 years (21 males) received subcutaneous REP 250 mg plus a nucleotide analogue weekly for 48 weeks. Twenty patients with no contraindications also received pegylated interferon-α (PegIFN) 45‒180 μg weekly. The investigators then assessed safety and efficacy, as well as intrahepatic markers in one liver explant.

Of the patients, 28 (85 percent) had treatment failure in the past, and six had decompensated cirrhosis (ascites in five). Twenty-one patients showed suboptimal responses to REP and had dose modifications (250 mg intravenously [IV] or 500 mg subcutaneously or IV) and/or treatment extension.

HDV RNA decreased at end of therapy by >2 log₁₀ in 23 patients (70 percent) and was undetectable in 19 (58 percent), while HBsAg loss happened in nine (27 percent). Among the 28 patients with available follow-up, undetectable HDV RNA and HBsAg persisted in 13 (46 percent) and five (18 percent), respectively. Half of these (14/28, 50 percent) achieved normalized ALT.

Responses were similar with or without PegIFN. Two of five patients affected by ascites showed improvements, while three underwent liver transplantation while receiving REP without complications. One liver explant had undetectable HDV RNA and HDAg, with very low intrahepatic covalently closed circular DNA activity and HBsAg levels. REP-related serious adverse events did not occur.

“Overall, REP demonstrated promising efficacy and acceptable tolerability in this difficult-to-treat population and warrants evaluation in a response-guided clinical trial,” the investigators said.