Eiger BioPharmaceuticals announced positive FDA guidance from a discussion on the Hepatitis Delta Virus (HDV) program in February, including agreement that a single, registration trial in HDV can support an NDA filing.
D-LIVR (Delta Liver Improvement and Virologic Response in HDV) is expected to be an international, multi-center, Phase 3 study of approximately 300 patients to evaluate an all-oral arm of lonafarnib (LNF) + ritonavir (RTV) and a combination arm of LNF + RTV + pegylated interferon-alfa (PEG IFN-α), with each arm to be compared to a placebo arm (background HBV nucleos(t)ide only), in HDV-infected patients. A PEG IFN-α alone arm will be dosed to demonstrate contribution of effect only. The LNF containing arms will not be required to demonstrate superiority over PEG IFN-α alone. The company is currently defining primary and secondary endpoints with the FDA.
"We are very pleased by the collaborative discussion with FDA and look forward to our planned advancement of the Phase 3 program for chronic HDV later this year," said David Apelian, MD, PhD, MBA, Chief Operating Officer and Executive Medical Officer.
The agency discussion also supported the development of pegylated interferon lambda (Lambda) in HDV infection and based on that discussion Eiger plans a Phase 2 study of Lambda in combination with LNF and RTV. LIFT (Lambda InterFeron combo-Therapy) is an open-label, Phase 2 study evaluating Lambda + LNF + RTV in approximately 26 HDV-infected patients. Patients will be dosed for 24 weeks + undergo follow up for 24 weeks. Primary endpoint will be ≥ 2 log decline in HDV RNA at end of treatment. Secondary endpoints will include histology (>2 point improvement in histological activity index and no progression in fibrosis) at end of treatment. LIFT will be conducted within the National Institutes of Health (NIH) at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and enrollment is planned for 2Q 2018.
Lonafarnib is a well-characterized, late-stage, orally active inhibitor of farnesyl transferase, an enzyme involved in modification of proteins through a process called prenylation. HDV uses this host cell process inside liver cells to complete a key step in its life cycle. Lonafarnib inhibits the prenylation step of HDV replication inside liver cells and blocks the virus life cycle at the stage of assembly. Lonafarnib has been dosed in over 120 HDV-infected patients across international academic centers and is in Phase 2 development for HDV. Lonafarnib has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), and Fast Track Designation by U.S. FDA. Lonafarnib is not approved for any indication, and is licensed from Merck Sharp & Dohme Corp. (known as MSD outside of the United States and Canada).