Results from the REP 301 and REP 401 studies showed combination therapy with REP2139 and pegylated interferon led to high rates of hepatitis B seroconversion in patients coinfected with hepatitis B and hepatitis D with more than half of treated patients also achieving functional cure of hepatitis D, according to data presented at HEP DART 2019.
“The REP 301 and REP 401 studies are the only studies to date using an investigational agent — nucleic acid polymers or NAPs — which has demonstrated long-term functional cure of HBV, HBV/HDV coinfection, and normalization of liver function with reversal of inflammation and fibrosis,” Andrew Vaillant, PhD, chief scientific officer at Replicor, told Healio Gastroenterology and Liver Disease.
Vaillant and colleagues designed the REP 401 study to examine the safety and efficacy of combination therapy with tenofovir disoproxil fumarate (TDF), pegylated interferon alfa-2a (pegIFN) and two NAPs (REP 2139 and REP 2165) in 40 patients with chronic HBV who tested HBV e-antigen negative . Patients received treatment for 48 weeks.
Therapeutic outcomes from REP 401 showed seroconversion in 53% of patients, with 39% achieving virologic control and 39% achieving functional cure. Additionally, the investigators estimated that 78% achieved a clinical benefit including lowered risk for progression and risk for hepatocellular carcinoma.
Investigators of the REP 301-LTF study followed 12 HBeAg-negative patients coinfected with HBV/HDV who previously received treatment with REP 2139 for 15 weeks, REP 2139 with pegIFN for 15 weeks, then pegIFN for 33 weeks. Follow-up was approximately 3.5 years.
In this study, 64% of patients achieved functional cure of HDV and 82% achieved a 2 log 10 or more reduction in HDV RNA from baseline. More than half of the patients also achieved normal alanine aminotransferase (73%) and normal or declining liver stiffness (64%).
“Replicor believes that REP 2139-[magnesium] based combination therapy will become the new standard of care for the treatment of HBV and HBV/HDV infection,” Vaillant said. – by Talitha Bennett
Reference: Bazinet M, et al. Transaminase flares during HBsAg reduction to < 1 IU/mL are correlated with the establishment of functional cure of HBV following NAP-based combination therapy. Presented at: HEP DART 2019; Dec. 12-19, 2019; Kauai, Hawaii.
Disclosures: Vaillant reports being an employee and shareholder in Replicor.