Related Experiment Video
Updated: Jun 3, 2025
Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B
Jinlin Hou1, Wenhong Zhang1, Qing Xie1
1From the Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University (J.H., X.L.), and the State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Institute of Hepatology, Nanfang Hospital (J.H.), Guangzhou, the Department of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University (W.Z.), the Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Q.X.), Roche Holding (Q.B., E.C.), Roche Research and Development Center (C.C., Y.H.), and Takeda APAC Biopharmaceutical Research and Development (Q.B.), Shanghai, the Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, First Hospital of Jilin University, Changchun (R.H.), the Center of Infectious Diseases, Laboratory of Infectious and Liver Disease, Institute of Infectious Diseases, West China Hospital, Sichuan University, Chengdu (H.T.), and the Department of Medicine and State Key Laboratory of Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong (M.-F.Y.) - all in China; the Division of Infectious Diseases, University Hospital Álvaro Cunqueiro, Galicia Sur Health Research Institute, Servizo Galego de Saúde-Universidade de Vigo, Vigo, Spain (L.E.M.A.); the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital (S.-S.Y.), and the Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University (C.-Y.P.), Taichung, the Department of Internal Medicine, Changhua Christian Hospital, Changhua (W.-W.S.), Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung (W.-L.C.), and National Taiwan University Hospital, Taipei (J.-H.K.) - all in Taiwan; the Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea (D.J.K.); the HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center and the Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok (A.A.), and the Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai (A.L.) - both in Thailand; Université de Paris-Cité, Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Centre de Recherche sur l'Inflammation, INSERM Unité Mixte de Recherche 1149, Paris (T.A.); F. Hoffmann-La Roche, Basel, Switzerland (F. Canducci, M.T.C., F. Chughlay, K.G., N.G., P.K., R.K., M.T.); Roche Products, Welwyn Garden City (S.D., V.P., B.S., R.U., C.W.), and ID Pharma Consultancy, Yelverton (C.W.) - both in the United Kingdom; Enthera Pharmaceuticals, Milan (F. Canducci); Parexel International, Hyderabad, India (A.P.); and the New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand (E.G.).
Background:
Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.
Methods:
We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.05 IU per milliliter) at 24 weeks after the end of treatment. Safety was also assessed.
Results:
Among 159 participants (30, 30, 34, 30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval [CI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5. In groups 1 through 5, respectively, HBsAg seroconversion occurred in 3%, none, 3%, 20%, and none of the participants at 24 weeks after the end of treatment. HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter. In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17%, 10%, 18%, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level.
Conclusions:
Among participants with chronic HBV infection who had virologic suppression with NA therapy, treatment with xalnesiran plus an immunomodulator resulted in HBsAg loss at 24 weeks after the end of treatment in a substantial percentage of participants. Grade 3 or 4 adverse events were not uncommon. (Funded by F. Hoffmann-La Roche; Piranga ClinicalTrials.gov number, NCT04225715.).
Related Concept Videos
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids