Abstract: INFO12-SA
Tissue-Targeted Complement Inhibition in Rare Kidney Diseases: A Phase 2 Open-Label Basket Trial of Ebribafusp Alfa
Session Information
- Informational Posters - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Borgi, Lea, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Gagne, Natalie, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Description
Glomerulopathies including IgA nephropathy, lupus nephritis, and complement 3 glomerulopathy are associated with complement activation in the kidneys. Ebribafusp alfa (EBRI) is an investigational, next-generation, tissue-targeted, anti-C3d-factor H fusion protein complement inhibitor. Complement factor H regulates the alternative complement pathway by binding to and inactivating the C3 convertase (C3bBb) and thus preventing overactivation of the alternative pathway. EBRI prevents complement activity locally, without overt systemic complement inhibition, by inactivating complement convertases directly at the site of activation. In preclinical models, EBRI reduced C3 convertase activity, proteinuria, and glomerular complement activation, and preserved podocyte foot processes. EBRI was generally well tolerated in a phase 1 trial in healthy participants, and after single intravenous doses of EBRI there was dose-dependent systemic alternative pathway inhibition without inhibition of the classical pathway. In contrast, subcutaneous doses were not associated with significant systemic alternative pathway inhibition.
This phase 2 trial will evaluate the safety, pharmacokinetics/pharmacodynamics, and clinical activity of EBRI in patients with rare kidney diseases, including IgA nephropathy, lupus nephritis, or complement 3 glomerulopathy. The trial is a single-arm, open-label, basket design. Approximately 30 participants with IgA nephropathy, lupus nephritis, or complement 3 glomerulopathy will be enrolled. EBRI will be administered subcutaneously at 450 mg once weekly for 26 weeks followed by a 4-week follow-up period, with a separate long-term extension. The incidence of adverse events is the primary endpoint. Secondary endpoints include changes in urine protein-to-creatinine ratio and estimated glomerular filtration rate from baseline to week 26 and the plasma pharmacokinetic profile. Urine-soluble C5b9 will be measured as a biomarker of kidney complement activation.
The trial is open to enrollment. To be a participating investigator or referring physician, please email trials@akebia.com.
Funding
- Akebia Therapeutics, Inc.