Maze Therapeutics could be set to challenge Vertex Pharmaceuticals as its kidney disease drug has shown benefit in a Phase II trial.
Maze’s MZE829, an oral, small molecule, dual-mechanism APOL1 inhibitor, led to a clinically meaningful mean reduction in proteinuria, as measured by urinary albumin-to-creatinine ratio (uACR), of 35.6% at week 12 in patients with broad APOL1-mediated kidney disease (AMKD).
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In the open-label, basket HORIZON trial (NCT06830629), 50% of patients treated with the study drug achieved a greater than 30% reduction in uACR.
In focal segmental glomerulosclerosis (FSGS) patients, treatment with MZE829 led to a mean reduction in uACR of 61.8%. In patients with AMKD without diabetes, treatment with MZE829 resulted in a clinically meaningful mean reduction in uACR of 48.6%. In patients with AMKD with diabetes, five patients were evaluable per protocol for efficacy, with two patients achieving at least a 30% reduction in uACR.
MZE829 was well-tolerated across all doses evaluated, with no serious adverse events (AEs) or severe treatment-related adverse events (TRAEs) observed.
Patients enrolled on the study were diagnosed with broad AMKD carrying the APOL1 high-risk genotype, including diabetic and non-diabetic patients and non-diabetic patients with severe focal segmental glomerulosclerosis (FSGS). Patients had to be on a stable background therapy for chronic kidney disease (CKD) for at least eight weeks, such as SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs).
Based on the data, Maze will continue enrollment in the HORIZON trial and will advance MZE829 into a pivotal program in patients with AMKD.
Dr Harold Bernstein, president of R&D and CMO of Maze, said: “We are pleased to show initial promising proof-of-concept for MZE829, an oral precision medicine that was designed to treat the underlying cause of AMKD by uniquely inhibiting both pore formation and channel function in the podocyte. Based on the data shown today, as well as genetics data derived through our Compass platform, we believe that MZE829’s dual mechanism approach has the potential to address the unmet need in AMKD patients.”
This data suggests Vertex could be in for competition with its investigational candidate inaxaplin, which has the same target as Maze’s drug. Vertex’s therapy led to an average 47.6% drop in proteinuria from baseline at 13 weeks in AMKD patients with FSGS in a Phase IIa trial. The drug is in a Phase II/III study.
Maze, which went public in January 2025, saw its stock sink 18.3% at market open on 25 March; however, this also came as the company announced financials for the year, which may have had some impact on the figure. The company’s stock closed at $49.00 on 24 March and opened at $40 on 25 March, with the price continuing to drop during the day to a low of $29.77 (correct at 12pm EST).
