The FDA has accepted EIT Pharma’s new drug application (NDA) for review for lonafarnib, an investigational oral therapy for chronic hepatitis D (CHD), the company announced.1 If approved, lonafarnib would become the first oral treatment option for the disease in the United States, where no FDA-approved oral therapies currently exist.
CHD is a serious, life-threatening liver disease caused by hepatitis D virus (HDV) that occurs only in people who also have hepatitis B virus infection.1 The disease can progress rapidly to cirrhosis, liver failure, liver cancer, and death, and treatment options remain limited.1 Lonafarnib is a first-in-class oral therapy candidate designed to target a key step in the HDV life cycle, and it is currently the only oral therapeutic candidate in late-stage clinical development for CHD.1 The drug has previously received FDA breakthrough therapy, fast track, and orphan drug designations.1
"Patients living with chronic hepatitis D urgently need novel therapies that target distinct steps in the HDV life cycle," Jeffrey Glenn, MD, PhD, co-founder of EIT Pharma and Joseph D. Grant Professor of Medicine and Microbiology & Immunology at Stanford University, said in a statement.1 Glenn said the NDA acceptance is an important first step toward giving patients with CHD a new treatment option, and that the company looks forward to working closely with the FDA throughout the review process.1
NDA supported by phase 3 D-LIVR study, the largest clinical trial conducted to date in chronic hepatitis D
What Infectious Disease Specialists Need to Know
What did the D-LIVR trial evaluate?
D-LIVR was a global, randomized, placebo-controlled phase 3 trial that enrolled more than 400 patients with CHD across 21 countries and evaluated lonafarnib-based regimens over 48 weeks.
Are there any FDA-approved treatments for CHD currently?
Bulevirtide (Hepcludex), an injectable therapy, was approved by the FDA in May 2026 as the first treatment for CHD. No oral therapy is currently approved.
What regulatory designations has lonafarnib received?
Lonafarnib has previously received FDA breakthrough therapy, fast track, and orphan drug designations for CHD.
The NDA is supported by data from the phase 3 D-LIVR study (NCT03719313), described by the company as the largest clinical trial conducted to date in CHD, along with phase 1/2 clinical data, nonclinical data, and manufacturing information.1 The global, randomized, placebo-controlled trial enrolled more than 400 patients across 21 countries and evaluated lonafarnib-based regimens over 48 weeks. If approved, lonafarnib would join bulevirtide, an injectable therapy the FDA approved in May 2026 as the first treatment for CHD overall, as the second approved CHD therapy in the US and the first delivered orally.2
The NDA draws on efficacy and safety data from the phase 3 D-LIVR trial, which randomized 407 patients with CHD 7:5:2:2 into an all-oral lonafarnib/ritonavir arm (n = 178), a triple-combination arm adding peginterferon alfa-2a (n = 125), a peginterferon alfa monotherapy comparator (n = 52), and placebo (n = 52), all maintained on background anti-HBV nucleos(t)ide therapy.3 At week 48, the composite primary endpoint, a 2-log or greater decline in HDV RNA plus ALT normalization, was met by 10.1% of patients in the all-oral arm and 19.2% of patients in the combination arm, both statistically significant improvements over the 1.9% response seen with placebo (P = .0044 and P <.0001, respectively).¹,² Response in the peginterferon comparator arm has been reported inconsistently across sources, ranging from roughly 10% to 38%, a discrepancy that has not been fully reconciled in publicly available data.3,4
Serious treatment-emergent adverse events (AEs) occurred in 8% of patients in the all-oral arm and 14% of those in the combination arm, compared with 10% in the peginterferon group and 4% with placebo, and most AEs were mild to moderate and gastrointestinal in nature, primarily nausea and diarrhea.3 Discontinuation rates were 9% in the all-oral arm and 8% in the combination arm, versus 2% in both the peginterferon and placebo groups at week 48, though rates rose to 19% overall by the week 72 follow-up. A small number of deaths occurred during the study; investigators attributed 1, in the peginterferon arm, to drug-related decompensated cirrhosis, while a death in the lonafarnib/ritonavir arm was deemed unrelated to study treatment.3,4
D-LIVR's design built on results from LOWR-2, an open-label phase 2 dose-finding study of 55 patients with CHD published in Hepatology.5 In that trial, the same composite virologic endpoint was reached by 46% of patients (6 of 13) receiving all-oral low-dose lonafarnib plus ritonavir and by 89% of patients (8 of 9) receiving the triple combination with peginterferon alfa, findings the D-LIVR investigators cited in selecting their phase 3 dosing regimens.5 Across the full clinical program, lonafarnib has now been dosed in more than 400 patients with HDV infection across phase 2 and phase 3 studies combined.
Next steps for lonafarnib in FDA pathway
EIT Pharma acquired the late-stage lonafarnib program in 2024, originally developed at Eiger BioPharmaceuticals, which has faced setbacks with other CHD-program assets, and has since worked with regulators and scientific collaborators to complete the NDA submission. The company is now preparing for potential commercialization while the FDA review is ongoing. If approved, lonafarnib's oral administration and room-temperature storage may offer practical advantages over existing management approaches for patients and clinicians weighing treatment burden, duration, and accessibility.1
"FDA acceptance of our NDA is an important milestone in our mission to bring a potential new oral treatment to people living with chronic hepatitis D," Leen Kawas, PhD, chief executive officer of EIT Pharma, said in a statement.1 Kawas credited the patients, investigators, and researchers involved in the D-LIVR study for making the milestone possible.
References
EIT Pharma, Inc. EIT Pharma Announces FDA Acceptance of New Drug Application for Lonafarnib for Treatment of Chronic Hepatitis D. News release. Published August 11, 2026. Accessed August 11, 2026. https://www.prnewswire.com/news-releases/eit-pharma-announces-fda-acceptance-of-new-drug-application-for-lonafarnib-for-treatment-of-chronic-hepatitis-d-302847501.html
Contagion. Hepatitis Month in Review: May. Published June 16, 2026. Accessed August 11, 2026. https://www.contagionlive.com/view/hepatitis-month-in-review-may
Etzion O, Hamid S, Lurie Y, et al. Week 48 results of the phase 3 D-LIVR study: a randomized double-blind, placebo-controlled trial evaluating the safety and efficacy of lonafarnib-boosted with ritonavir with or without peginterferon alfa in patients with chronic hepatitis delta. Presented at: EASL Congress; June 21-24, 2023; Vienna, Austria.
Yurdaydin C, Keskin O, Yurdcu E, et al. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology. 2022;75(6):1551-1565.
