Abstract: SA-OR089
Farabursen Increases Urinary Polycystin-1 and Polycystin-2 and Reduces Height-Adjusted Total Kidney Volume Growth in Patients with ADPKD
Session Information
- Late-Breaking Research Orals - 3
November 08, 2025 | Location: Grand Ballroom C, Convention Center
Abstract Time: 04:42 PM - 04:54 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Yu, Alan S.L., The University of Kansas Medical Center, Kansas City, Kansas, United States
- Garg, Rekha, Regulus Therapeutics, a Novartis Company, San Diego, California, United States
- Bellovich, Keith A., St. Clair Nephrology Research, Detroit, Michigan, United States
- Silva, Arnold L., Boise Kidney and Hypertension Institute, Boise, Idaho, United States
- Chebib, Fouad T., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Padgett, Claire, Regulus Therapeutics, a Novartis Company, San Diego, California, United States
- Lee, Edmund Chun Yu, Regulus Therapeutics, a Novartis Company, San Diego, California, United States
- Valencia, Tania M., Regulus Therapeutics, a Novartis Company, San Diego, California, United States
- Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Carroll, Kevin, KJC Statistics Limited, Cheadle, United Kingdom
- Patel, Vishal, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
ADPKD is caused by heterozygous loss-of-function mutations in PKD1 or PKD2, leading to progressive renal cystogenesis and kidney failure. miR-17 family suppresses PKD1 and PKD2, providing a therapeutic rationale for miR-17 inhibition to restore polycystin (PC) levels. Farabursen, an anti–miR-17 oligonucleotide, de-represses miR-17 mRNA targets, including PKD1 and PKD2, leading to increased PC1 and PC2 and amelioration of preclinical PKD.
Methods
A randomized, double-blind, placebo-controlled trial evaluated farabursen in patients with ADPKD across 3 weight-based cohorts (1, 2, and 3 mg/kg) and a fixed dose of 300 mg in an open-label cohort. Key entry criteria were Mayo Class 1C, 1D, or 1E, and eGFR 30-90 mL/min/1.73 m2. Patients received subcutaneous injection Q2W for 12 weeks (7 doses), with a 4-week post-treatment follow-up. Primary endpoints were safety and changes in urinary PC1 and PC2; secondary endpoint was MRI-measured height-adjusted total kidney volume (htTKV).
Results
We enrolled 68 patients (58 farabursen, 10 placebo) with generally balanced baseline characteristics. Farabursen was well tolerated. Increases in PC1 and PC2 were shown for 2, 3 mg/kg and 300 mg fixed doses versus placebo (p<0.05 for PC1 and PC2 for each dose). A reduction in htTKV growth for 2 mg/kg and higher doses was shown vs placebo (Fig 1). In a pooled analysis of 2 mg/kg and higher dose groups, htTKV growth increased by 0.24% vs 2.85% in the placebo. This effect was independent of genotype and Mayo Class.
Conclusion
Farabursen showed dose-dependent target engagement on PC1 and PC2. Treatment with 2, 3 mg/kg and 300 mg doses of farabursen over 12 weeks suggests a mean halting of htTKV growth. Out results demonstrate the potential of farabursen as a therapeutic agent for ADPKD. A Phase 3 registrational trial is planned.
Figure 1: Percent Change in htTKV
Funding
- Commercial Support – Regulus Therapeutics, a Novartis Company