Abstract: SA-OR053
Evaluation of Safety, Tolerability, and Efficacy of MZE829 in Adults with APOL1-Mediated Kidney Disease (HORIZON Study)
Session Information
- Glomerular Diseases: Clinical Trial Results
October 24, 2026 | Location: Mile High Ballroom 4A, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Limb, Susan, Maze Therapeutics Inc, South San Francisco, California, United States
- Boundy, Keith, Maze Therapeutics Inc, South San Francisco, California, United States
- Guan, Shanhong, Maze Therapeutics Inc, South San Francisco, California, United States
- Humeniuk, Rita, Maze Therapeutics Inc, South San Francisco, California, United States
- Geib, Till, Maze Therapeutics Inc, South San Francisco, California, United States
- Trachtman, Howard, Northwell Health, New Hyde Park, New York, United States
- Bramham, Kate, King's College London, London, England, United Kingdom
- Olabisi, Opeyemi A., Duke University, Durham, North Carolina, United States
- Campbell, Kirk N., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Lazar, Andrew, University Hospitals Health System, Cleveland, Ohio, United States
- Lentine, Krista L., Saint Louis University, St. Louis, Missouri, United States
- Coppock, Gaia M., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Bernstein, Harold S., Maze Therapeutics Inc, South San Francisco, California, United States
Background
APOL1 high risk genotype is associated with an increased risk of Chronic Kidney Disease (CKD) and faster progression to Kidney Failure (KF). HORIZON evaluates the safety, tolerability, and effect on albuminuria of MZE829, a novel APOL1 inhibitor, in individuals with APOL1-mediated kidney disease (AMKD) and albuminuria.
Methods
HORIZON is an ongoing Phase 2, open-label study of MZE829 in adults aged 18 to 68 years with AMKD and persistent albuminuria (NCT06830629). Participants are required to be on stable standard-of-care CKD medications for at least 8 weeks prior to study. Participants receive MZE829 250mg once daily for 12 weeks followed by a 4 week follow up period.
An administrative analysis was performed on 15 participants who had finished the 12-week treatment period as of February 27, 2026.
Results
The analysis includes 7 participants with diabetes and 8 participants without diabetes (5 of 8 with FSGS). Baseline characteristics for the 15 participants were: mean age 49.1 years, 53% male, mean (90% CI) urinary albumin-to-creatinine ratio (UACR) 1113.7±812.8 mg/g, and mean eGFR (90% CI) 41.9±13.5 mL/min/1.73 m2. The majority were on ≥2 background CKD medications. No serious adverse events (SAEs) or severe treatment-related treatment-emergent AEs (TR-TEAEs) were observed. The most common TR-TEAEs were mild and moderate diarrhea (n=2) and headache (n=2). No clinically significant changes in labs, ECG, vital signs, or physical exams were observed.
For the efficacy-evaluable participants with a Week 12 assessment (n=12), the mean reduction in UACR was -35.6% [HSB1] [TG2] (90% CI [-53.3, -11.4], 50.0% responders[SL3] [TL4] ). The largest mean UACR reduction was observed in participants with FSGS: -61.8% (90% CI [-81.4, -21.6], 75.0% responders). No correlation between baseline UACR or eGFR and treatment response was observed.
Higher plasma trough concentrations of MZE829 were associated with larger UACR reductions.
Conclusion
MZE829 was generally well-tolerated when administered for 12 weeks in addition to standard-of-care. MZE829 showed a notable[MK1] reduction in proteinuria in a broad AMKD population, with the largest, most consistent reduction observed in participants with FSGS. Overall, these results support[MK2] further evaluation of MZE829 in AMKD.
Funding
- Commercial Support – Maze Therapeutics