peginterferon lambda-1a (BMS-914143) / Eiger, Stanford University, BMS - LARVOL DELTA

Hope on the horizon: Emerging therapies for hepatitis D. (PubMed, World J Hepatol) - "Pegylated interferon lambda acts on interferon-lambda (Type III) receptors predominantly expressed in hepatocytes. In 2023, bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D. This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells, which is the primary entry point for the virus...Two more viral entry inhibitors are HH003 and tobevibart. Other agents include nucleic acid polymers (REP 2139-Mg), prenylation inhibitors (lonafarnib), and RNA interference-based therapies (elebsiran)...The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1, 2, and 3 trials. With these new treatments on the horizon, the prospects for improved HDV patient outcomes are promising."

Journal • Review • Hepatitis B • Infectious Disease • Inflammation • IFNA1

Current and future therapeutic options for chronic hepatitis D virus infection. (PubMed, Front Cell Infect Microbiol) - "The old weapons are PegIFNα and recently PegIFN-lambda (PegIFNλ). PegIFNα, for which there are more data, appears to be an excellent combination regimen, if not contraindicated, both for Bulevirtide (BLV), data supported by important clinical trials and real-world studies, and probably for lonarfanib, although in the latter case the results are not yet definitive as the studies are fewer. However, data on long-term follow-up are needed."

Journal • Review • Hepatology • Infectious Disease • Inflammation • IFNA1

Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies. (PubMed, Gut) - "In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis...The PegIFN lambda study has been discontinued due to liver toxicity issues, while lonafarnib boosted with ritonavir showed limited off-therapy efficacy in a phase 3 study. Nucleic acid polymer-based therapy is promising but large studies are still lacking. New controlled trial data come from molecules, such as monoclonal antibodies and/or small interfering RNA, that target HBsAg or HBV RNAs, which demonstrated not only profound HDV suppression, but also HBsAg decline.While waiting for new compounds to be approved as monotherapy or in combination, BLV monotherapy 2 mg/day remains the only approved therapy for CHD, at least in the European Union region."

Journal • Review • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • IFNA1

The Forgotten Virus, Hepatitis D: A Review of Epidemiology, Diagnosis, and Current Treatment Strategies. (PubMed, J Clin Exp Hepatol) - "There are no current treatments in the United States that are Food and Drug Administration (FDA)-approved for the treatment of HDV; however, bulevirtide (BLV) is approved in the European Union conditionally and is under review with the United States FDA...There are other therapies in development globally that have shown promise, including BLV, pegylated-interferon-lambda (PEG-IFN-lambda), and lonafarnib (LNF)...The PDUFA date for BLV in the United States is mid-2024. Current studies with both BLV and LNF are limited in providing sustained virological response (SVR); future trials will need to demonstrate more substantial SVR with possible triple combination trials as options."

Journal • Review • Hepatitis B • Hepatology • Infectious Disease • Inflammation

ILIAD: Interferon Lambda for Immediate Antiviral Therapy at Diagnosis in COVID-19 (clinicaltrials.gov) - P2 | N=157 | Completed | Sponsor: University Health Network, Toronto | Recruiting ➔ Completed | N=240 ➔ 157

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Repurposed Approved and Under Development Therapies for Patients With Early-Onset COVID-19 and Mild Symptoms (clinicaltrials.gov) - P3 | N=6246 | Recruiting | Sponsor: Cardresearch | Trial completion date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Oct 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

EVALUATING THE EFFICACY OF PEGYLATED IFN-LAMBDA AND IFN-ΑLFA TREATMENTS ON HBV AND HDV INFECTIONS IN HUMANIZED MICE (AASLD 2023) - "In contrast to our findings in immune competent patients (ibid), Alfa was more effective than Lambda in decreasing HBV DNA, HDV RNA, and HBsAg during treatment in humanized mice that lack of an adaptive immune response, suggesting that Alfa induces stronger innate immune responses than Lambda. The respective roles of the combined innate and adaptive immune systems in the antiviral efficacy of Alfa and Lambda against HBV and HDV requires further study."

Preclinical • Genetic Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Primary Immunodeficiency • IFNA1

Bulevirtide and emerging drugs for the treatment of hepatitis D. (PubMed, Expert Opin Biol Ther) - "Additionally, we review ongoing trials of emerging drugs for HDV such as pegylated interferon lambda and lonafarnib. Bulevirtide was generally well tolerated, and no serious adverse events occurred. Understanding the true prevalence of HDV, as well as continued studies of emerging drugs will prove valuable to the larger goal of eradication of Hepatitis D."

Journal • Review • Hepatitis B • Hepatology • Infectious Disease • Inflammation

LIMT-2: Phase 3 Study to Evaluate the Efficacy and Safety of Peginterferon Lambda for 48 Weeks in Patients With Chronic HDV (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Eiger BioPharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Infectious Disease • Inflammation

DIMENSION: Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV (clinicaltrials.gov) - P3 | N=453 | Terminated | Sponsor: Bristol-Myers Squibb | Completed ➔ Terminated; Sponsor decision not based on any new unexpected safety findings or efficacy observations.

Combination therapy • Trial termination • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Pegylated Interferon Lambda for Covid-19. (PubMed, N Engl J Med) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Pegylated Interferon Lambda for Covid-19. (PubMed, N Engl J Med) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Pegylated Interferon Lambda for Covid-19. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial. (PubMed, Hepatology) - "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."

Journal • P2 data • P2 data • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Emerging drugs for hepatitis D. (PubMed, Expert Opin Emerg Drugs) - "Virus entry inhibitor bulevirtide has received conditional approval by the European Medicines Agency...It is associated with dose-dependent gastrointestinal toxicity and is better used with ritonavir which increases liver lonafarnib concentrations...PegIFN lambda is associated with less IFN typical side effects. In a phase 2 study it led to 6 months off treatment viral response in one third of patients."

Journal • Gastrointestinal Disorder • Hepatology • Immune Modulation • Infectious Disease • Inflammation

Pegylated Interferon Lambda for Treatment of COVID-19 Infection (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Soroka University Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Interferon lambda as a potential treatment for COVID-19. (PubMed, Expert Opin Biol Ther) - "Pegylated interferon lambda substantially reduced the risk of COVID-19-related hospitalizations or emergency room visits in a recent phase 3, multi-center, randomized, double-blind, placebo-controlled study of high-risk, non-hospitalized adult patients with SARS-CoV-2 infection compared to treatment with placebo...Interferons have been used to treat viral infections, including hepatitis B and hepatitis C, and malignancies such as non-Hodgkin's lymphoma, as well as the autoimmune condition multiple sclerosis. This manuscript examines what is known about the role of interferon lambda in the treatment of COVID-19, including potential limitations, and explores how this approach may be used in the future."

Clinical • Journal • CNS Disorders • Hematological Malignancies • Hepatitis B • Hepatitis C • Hepatology • Immunology • Infectious Disease • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Emerging anti-HDV drugs and HBV cure strategies with anti-HDV activity. (PubMed, Liver Int) - "In this review, we summarize the ongoing efforts to evaluate promising HDV-specific drugs, such as lonafarnib (LNF), pegylated interferon lambda (PEG-IFN-λ) and their use as a combination therapy. Furthermore, we review the most recent developments in the area of anti-HBV drugs with potential effects against HDV, including therapeutic agents targeting hepatitis B surface antigen (HBsAg) expression, secretion and function. Finally, we consider the important insights that have emerged from the development of these potential antiviral strategies, as well as the intriguing questions that remain to be elucidated in this rapidly changing field."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

EFFECT OF EARLY TREATMENT WITH PEGYLATED INTERFERON LAMBDA FOR COVID-19 (CROI 2023) - No abstract available

Late-breaking abstract • Infectious Disease • Novel Coronavirus Disease

Early Treatment with Pegylated Interferon Lambda for Covid-19. (PubMed, N Engl J Med) - P3 | "Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.)."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Beyond bulevirtide: alternative therapeutic options for the management of HDV. (PubMed, J Viral Hepat) - "There is an urgent need to develop new drugs. In this article, we review antiviral treatments under development for HDV chronic infection (except Bulevirtide reviewed in a specific article), including those in the HBV cure program, outlining their respective mechanisms-of-action."

Journal • Review • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor

Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity. (PubMed, Nat Commun) - P2 | "We previously demonstrated that injection of pegylated interferon-lambda accelerated viral clearance in COVID-19 patients (NCT04354259)...However, we identify delayed T cell responses in older adults, suggesting that interferon-lambda can overcome delays in adaptive immunity to accelerate viral clearance in high-risk patients. Altogether, interferon-lambda offers an early COVID-19 treatment option for outpatients to boost innate antiviral defenses without dampening peripheral adaptive immunity."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

"Peginterferon lambda 1a" (@leroy98276276)

IFNL1

Clinical Trials in HDV: Measuring Success. (PubMed, Hepatology) - "Recently, a wave of new investigational therapies has come under evaluation, including bulevirtide, lonafarnib, pegylated interferon lambda (PEG-IFNλ), and REP-2139 creating new excitement in HDV. These clinical benefits may include reducing the risk of progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation, and mortality. However, the optimal way to measure success in HDV clinical trials remains unknown and will continue to evolve."

Journal • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor • Transplantation • IFNA1

Repurposed Approved and Under Development Therapies for Patients With Early-Onset COVID-19 and Mild Symptoms (clinicaltrials.gov) - P3 | N=6246 | Recruiting | Sponsor: Cardresearch | N=4669 ➔ 6246

Enrollment change • Infectious Disease • Novel Coronavirus Disease