Abstract

Background: Chronic Hepatitis Delta Virus (HDV) infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of the Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV.

Methods: Open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks followed by 24 weeks of post-treatment follow-up.

Results: 33 patients were allocated to Lambda 180 mcg (n=14) or 120 mcg

(n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-

364) and bilirubin 0.5 mg/dL (0.2-1.2). Intention to treat rates of virologic response

to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of

14 (36%) and 3 of 19 (16%), respectively. Post-treatment response rate of 50% was seen in low BL viral load (≤ 4 log10) on 180 mcg. Common on-treatment AEs included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation.

Conclusions: Treatment with Lambda in patients with chronic HDV may result in

virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.