Liver and Bile
Hepatology. 2023;77(6):2093–103
Treatment of chronic hepatitis D with peginterferon lambda – The phase 2 LIMT-1 clinical trial
Background and aims: Hepatitis D virus (HDV) infection leads to the most aggressive form of human viral hepatitis for which there is no Federal Drug Administration (FDA)-approved therapy. Peginterferon (PEG IFN)-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in hepatitis B virus (HBV) and hepatitis C virus (HCV) patients compared to PEG IFN-alfa. The goal of phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV.
Approach and results: An open-label study of Lambda 120 or 180 µg, administered once weekly by subcutaneous injections for 48 weeks, fol-lowed by 24 weeks of posttreatment follow-up. 33 patients were allocated to Lambda 180 µg (n = 14) or 120 µg (n = 19). Baseline mean values: HDV RNA 4.1 log10 IU/ml (SD ± 1.4); alanine aminotransferase 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 µg and 120 µg, 24 weeks following treatment cessation were 5 of 14 (36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low baseline viral load (≤ 4 log10) on 180 µg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight cases (24%) 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 re-duction or discontinuation.
Conclusions: Treatment with peginterferon lambda (Lambda) in patients with chronic hepatitis D may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.