Akebia Doses First Patient in Phase 2 Basket Trial of Ebribafusp for Rare Complement-Mediated Kidney Diseases
核心洞察
Akebia Therapeutics has dosed the first patient in an open-label Phase 2 basket trial of ebribafusp (搜索) in IgA nephropathy (搜索), lupus nephritis (搜索) and C3 glomerulopathy (搜索).
The trial will enroll up to 30 patients who receive once-weekly subcutaneous ebribafusp (搜索) for 26 weeks, followed by a long-term extension for responders.
The primary endpoint is adverse event incidence, with secondary endpoints including proteinuria by UPCR, kidney function by eGFR and pharmacokinetics.
Akebia Therapeutics, Inc. (Nasdaq: AKBA) announced that the first patient has been dosed in its Phase 2 basket trial evaluating ebribafusp (搜索) for the treatment of rare complement-mediated kidney diseases, including IgA nephropathy (搜索) (IgAN), lupus nephritis (搜索) (LN), and C3 glomerulopathy (搜索) (C3G). The open-label trial is expected to report initial data in 2027.
"Dosing the first patient in this basket trial is an important milestone for the ebribafusp (搜索) program and, more importantly, for patients living with rare kidney diseases," said Dr. Steven Burke, Chief R&D and Medical Officer at Akebia. "Ebribafusp is designed to inhibit complement activation directly in kidney tissue without suppressing the complement system in the blood. If successful, we believe this differentiated approach has the potential to provide patients with a long-term treatment option while reducing the infection risk associated with systemic complement inhibition and could have applicability across multiple rare kidney diseases."
Trial Design and Endpoints
The Phase 2 basket trial is designed to evaluate the safety, efficacy, and pharmacokinetics of ebribafusp (搜索) and is expected to enroll up to 30 patients with IgAN, LN or C3G. Patients will receive ebribafusp dosed once-weekly subcutaneously for 26 weeks in the main study, followed by a long-term extension study for responders.
The primary endpoint is the incidence of adverse events. Secondary endpoints include change in proteinuria measured by urine protein creatinine ratio (UPCR), kidney function measured by estimated glomerular filtration rate (eGFR), and pharmacokinetics. The trial will also measure blood and urine complement biomarkers to assess the extent to which ebribafusp (搜索) reduces complement activity in kidney tissue without inhibiting the complement system in the blood. Additional information about the trial is available at ClinicalTrials.gov under identifier NCT06419205.
Mechanism and Development History
Ebribafusp (搜索) (previously referred to as AKB-097 and ADX-097) is an investigational, next-generation anti-C3d (搜索) factor H (搜索) fusion protein and complement inhibitor. According to Akebia, the presence of C3d in glomeruli is a hallmark of numerous complement-mediated kidney diseases. Ebribafusp is designed to target the sites of complement activation in tissues to inactivate the alternative pathway C3 convertase (搜索), with the goal of targeting local, uncontrolled complement activity and inflammation at the site of kidney injury.
In November 2025, Akebia acquired the global rights to ebribafusp (搜索) from Q32 Bio, Inc. In nonclinical studies conducted by Q32 Bio, ebribafusp distributed to affected tissues and organs and demonstrated durable tissue pharmacokinetic and pharmacodynamic properties. In a completed Phase 1 clinical trial in healthy volunteers conducted by Q32 Bio, ebribafusp was observed to be generally well-tolerated and demonstrated minimal anti-drug antibodies.
Akebia Therapeutics describes itself as a fully integrated biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease. The company was founded in 2007 and is headquartered in Waltham, Massachusetts.