Cambridge, Massachusetts, August 3, 2026
Akebia Therapeutics, Inc. announced the initiation of an open-label Phase 2 basket trial of ebribafusp, its investigational next-generation complement inhibitor, in patients with rare complement-mediated kidney diseases. The study will evaluate ebribafusp in IgA nephropathy (IgAN), lupus nephritis (LN), and C3 glomerulopathy (C3G), assessing its safety, efficacy and pharmacokinetics. Previously known as AKB-097 and ADX-097, ebribafusp is an anti-C3d factor H fusion protein designed to inhibit complement activation at affected tissue sites while avoiding systemic inhibition of the complement system in the blood. Akebia expects to report initial data from the Phase 2 study in 2027.
Phase 2 Basket Trial Targets Three Rare Kidney Diseases
The Phase 2 basket trial is expected to enroll up to 30 patients with IgAN, lupus nephritis or C3G. Participants will receive ebribafusp through once-weekly subcutaneous dosing for 26 weeks during the main study, followed by a long-term extension study for patients who respond to treatment. The primary endpoint will assess the incidence of adverse events, while secondary endpoints will evaluate changes in proteinuria using urine protein creatinine ratio, kidney function measured by estimated glomerular filtration rate, and pharmacokinetics. Investigators will also measure blood and urine complement biomarkers to determine whether ebribafusp can reduce complement activity within kidney tissue without inhibiting the complement system circulating in the blood. In an earlier Phase 1 study involving healthy participants, once-weekly 450 mg subcutaneous dosing achieved the desired exposures for predicted tissue complement inhibition without inhibiting complement in the blood. The new trial will provide an important opportunity to assess whether this differentiated mechanism translates into therapeutic effects in patients with complement-mediated kidney disease.
Ebribafusp Designed for Tissue-Targeted Complement Inhibition
Ebribafusp is designed to localize to sites of complement activation in affected kidney tissue, potentially differentiating it from approaches that systemically inhibit the complement pathway. C3d deposits in glomeruli are a hallmark of several complement-mediated kidney diseases. Ebribafusp is designed to target these deposits and degrade the alternative pathway C3 convertase, potentially reducing complement activity where disease is occurring while preserving complement activity in the bloodstream. Akebia estimates that more than 200,000 patients in the United States are living with rare complement-mediated kidney diseases including IgAN, lupus nephritis and C3G. The company believes that avoiding systemic complement inhibition could potentially provide a safer long-term therapeutic strategy and reduce the risk of serious bacterial infections. These potential benefits, however, will need to be established through the ongoing clinical program. The Phase 2 trial will therefore provide critical evidence on the candidate’s safety, biological activity and early efficacy across multiple kidney diseases.
Advertisement
Akebia Expands Rare Kidney Disease Pipeline With Ebribafusp
Akebia acquired global rights to ebribafusp from Q32 Bio, Inc. in November 2025, adding the next-generation complement inhibitor to its kidney disease portfolio. In nonclinical studies previously conducted by Q32 Bio, ebribafusp distributed to affected tissues and organs and demonstrated durable tissue pharmacokinetic and pharmacodynamic properties. A completed Phase 1 study in healthy volunteers also found the candidate to be generally well tolerated with minimal anti-drug antibodies observed. The newly initiated Phase 2 basket trial represents the next major clinical test of the program and will help determine whether targeted complement inhibition can provide meaningful benefits across several complement-mediated renal diseases. Akebia, a fully integrated biopharmaceutical company focused on kidney disease, plans to use data from the study to evaluate the future development potential of ebribafusp. By studying IgA nephropathy, lupus nephritis and C3 glomerulopathy within a single basket trial, the company can investigate the candidate’s mechanism across multiple disorders characterized by complement activity in kidney tissue. Initial results expected in 2027 will provide an early indication of whether weekly subcutaneous ebribafusp can achieve targeted complement inhibition while maintaining systemic complement activity, potentially supporting further development as a differentiated treatment for patients with rare kidney diseases.
Source: Akebia Therapeutics press release
