Disclosures: Young-Suk Lim – Advisory Committees or Review Panels: Gilead Science, Bayer; Grant/Research Support: Gilead Science, Novartis, Bayer; Speaking and Teaching: BMS The following people have nothing to disclose: Gi-Ae Kim, Seungbong Han, Jihyun An Introduction: Therapy for chronic delta (HDV) hepatitis

infection is unsatisfactory with poor response rates to interferon. Prenylation inhibitors have Ruxolitinib demonstrated effectiveness against HDV in in vitro and in vivo models. As a proof-of-concept study, we evaluated the antiviral effect and safety of the prenylation inhibitor, lonafarnib in patients with chronic HDV. Methods: 14 HDV infected patients were enrolled into 2 groups in a phase 2a double-blinded, randomized, placebo-controlled study and received: Group 1 – lonafarnib 100 mg twice daily and Group 2 – lonafarnib 200 mg twice daily for 28 days followed by 6 months of off-therapy follow-up. Both groups enrolled 6 treatment and 2 placebo subjects, where Group 1 placebo Palbociclib supplier subjects were offered open-label lonafarnib as Group 2 participants. Patients underwent 72-hour viral kinetic and pharmacokinetic evaluations at the start of therapy. Serial measurements of safety parameters,

liver tests, pharmacokinetics, virologic (HDV RNA and HBV DNA) markers and symptom questionnaires were performed. Results: This ongoing study is completely enrolled and all patients have completed Baricitinib 28 days of therapy, and data is available on the first 15 of 16 patients. Patients enrolled were mostly males (71%) with a median age of 38 years and included Asian (50%), Caucasian (43%) and African (7%). Median baseline evaluations include: ALT (89 IU/mL), AST (61 IU/mL), Ishak fibrosis (3), HBV DNA (<21 IU/mL) and HDV RNA (1.01E+06 IU/mL). There were no differences in baseline parameters between therapeutic groups. After 28 days of therapy, the mean log HDV RNA change from baseline was -0.13 log IU/mL

in the placebo group (p=0.31), -0.74 log IU/mL in Group 1 (p=0.02) and -1.60 log IU/mL in Group 2 (p<0.0001), with half of patients in Group 2 achieving a decrease from baseline-to-nadir of greater than -2 log IU/mL. Lonafarnib serum concentrations correlated with HDV RNA change (R2=0.76, p<0.0001). Adverse events were mild to moderate and included nausea, vomiting, dyspepsia, anorexia, diarrhea, and weight loss. There were no treatment discontinuations for adverse events. Conclusions: This is the first demonstration that treatment of chronic HDV with the pre-nylation inhibitor lonafarnib significantly reduces virus levels in patients. The decline in virus levels significantly correlated with serum drug levels, providing further evidence for the efficacy of prenylation inhibition in chronic HDV.