Akebia starts Phase 2 basket trial of complement inhibitor ebribafusp
Akebia Therapeutics has initiated a Phase 2 basket trial evaluating ebribafusp, an anti-C3d factor H fusion protein, in patients with rare complement-mediated kidney diseases. The Cambridge, Massachusetts-based company is targeting three indications in a single study: IgA nephropathy (IgAN), lupus nephritis (LN), and C3 glomerulopathy (C3G).
The open-label trial will enrol up to 30 patients, who will receive once-weekly subcutaneous injections of ebribafusp for 26 weeks. Patients who respond will be eligible to continue into a long-term extension study. The primary endpoint is the incidence of adverse events, reflecting the early-stage safety focus of the programme, while secondary endpoints include changes in proteinuria measured by urine protein creatinine ratio, kidney function assessed by estimated glomerular filtration rate, and pharmacokinetics. Akebia says it expects to report initial data in 2027, with the trial registered on ClinicalTrials.gov under identifier NCT06419205.
The science and the asset
Ebribafusp, formerly known as AKB-097 and ADX-097, is designed to localise to glomeruli where C3d deposits have accumulated, targeting the sites of complement activation in tissues rather than systemically suppressing the complement pathway. The company says this tissue-selective approach could reduce the risk of serious bacterial infections, a well-documented safety liability of systemic complement inhibitors.
In a completed Phase 1 study in healthy volunteers, conducted by Q32 Bio before Akebia acquired global rights to the asset in November 2025, weekly 450 mg subcutaneous dosing achieved exposures consistent with predicted tissue complement inhibition while leaving blood complement activity largely intact. The drug was described as generally well-tolerated with minimal anti-drug antibody formation.
Dr Steven Burke, Chief R&D and Medical Officer at Akebia, said the trial aims "to demonstrate the safety, efficacy, and pharmacokinetics of weekly subcutaneous dosing of ebribafusp in reducing complement activation in the kidney without inhibiting the complement system in the blood." Akebia estimates that more than 200,000 patients in the United States are living with the three indications covered by the basket design.
Market context and competitive landscape
The complement inhibitor space has attracted significant commercial interest over recent years. Systemic complement blockers targeting the C3 or C5 nodes, such as approved agents for paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome, have established proof of concept but carry infection risk because of the sustained immunosuppression they cause. A tissue-targeted approach would represent a meaningful differentiation if the clinical profile holds up in diseased kidneys.
IgAN in particular has become a busy area, with several late-stage programmes and at least one recently approved therapy in the indication. The basket trial design Akebia has chosen is pragmatic given the small patient populations involved in LN and C3G, and it will allow the company to generate safety and pharmacodynamic data across all three indications simultaneously before committing to larger, single-indication pivotal studies.
For Akebia itself, the programme represents a significant strategic pivot. The company built its earlier commercial identity around vadadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor for anaemia in chronic kidney disease. Ebribafusp is a biologic asset with a different mechanism and a much earlier development profile, so investors will be watching the 2027 data readout closely to assess whether the acquisition from Q32 Bio has given the company a credible second platform in nephrology.