Regulus Therapeutics Announces Successful Completion of its Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of Farabursen (RGLS8429) for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Core Insights - Regulus Therapeutics announced positive topline results from the fourth cohort of its Phase 1b MAD study of farabursen for treating Autosomal Dominant Polycystic Kidney Disease (ADPKD) [2][4] - The study demonstrated a significant halting of kidney volume growth in patients receiving a 300 mg fixed dose of farabursen over four months [1][4] - The company is on track to initiate a Phase 3 pivotal trial in Q3 2025, with a focus on a 12-month endpoint for kidney volume change [2][6] Study Details - The Phase 1b MAD study was a double-blind, placebo-controlled trial assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of farabursen in adult ADPKD patients [3] - The study included three weight-based dose levels and one fixed dose level, with primary endpoints focused on urinary PC1 and PC2 changes, and an exploratory examination of htTKV growth rate [3][4] - In the fourth cohort, 26 subjects received 300 mg of farabursen bi-weekly for three months, showing consistent mechanistic responses and halting htTKV growth [4][5] Efficacy and Safety - Patients treated with farabursen showed a mean htTKV growth rate of 0.05%, compared to 2.58% in placebo subjects, indicating a significant reduction in kidney volume growth [5] - Urinary levels of PC1 and PC2 increased significantly, correlating with the observed effects on kidney volume [5] - Farabursen demonstrated a favorable safety and tolerability profile, consistent with earlier cohorts, with no serious adverse events reported [5][9] Future Plans - The company has confirmed alignment with the FDA regarding the Phase 3 trial design, which includes a 12-month htTKV endpoint for Accelerated Approval and a 24-month eGFR endpoint for Full Approval [6][9] - Regulus aims to advance farabursen as a potential treatment option for ADPKD, addressing a significant unmet medical need [6][10] Background on ADPKD - ADPKD is a common genetic disorder characterized by the development of multiple cysts in the kidneys, leading to end-stage renal disease in approximately 50% of patients by age 60 [8] - The disease affects around 160,000 individuals in the U.S., with a global prevalence estimated between 4 to 7 million [8]