Regulus Therapeutics Reports Promising Outcomes in ADPKD Clinical Trials with Farabursen

Regulus Therapeutics' Encouraging Updates on ADPKD Trials

Regulus Therapeutics Inc. has recently made headlines with promising updates regarding their clinical trials for treating Autosomal Dominant Polycystic Kidney Disease (ADPKD) using their innovative drug, farabursen (RGLS8429). The company disclosed positive topline results from an interim analysis of the Phase 1b Multiple-Ascending Dose (MAD) clinical trial.

Overview of the Study

The Phase 1b MAD study is a critical double-blind, placebo-controlled trial aimed at evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of farabursen in adult ADPKD patients. This study is unique as it examines various weight-based doses along with a fixed dose to measure changes in essential biomarkers, including urinary polycystins 1 and 2 (PC1 and PC2), total kidney volume adjusted for height (htTKV), and overall kidney function.

In the fourth cohort of this study, which comprised 26 subjects, participants received a fixed dose of 300 mg of farabursen biweekly for three months. Interim efficacy analyses from the first 14 subjects indicated a continued positive mechanistic dose response observed through modifications in urinary PC1 and PC2 levels, alongside a noteworthy reduction in the htTKV growth rate.

Key Findings from Cohort 4

1. Biomarker Levels: The effects on polycystin biomarker levels in the fourth cohort closely mimicked those in the third cohort at the 3 mg/kg dose, likely yielding optimal kidney exposure.
2. Kidney Growth Rate Impact: Exploratory results indicated a significant impact on htTKV growth rate after three months of treatment, which was consistent across various patient classifications.
3. Safety Profile: The complete safety assessment across all 26 participants revealed that farabursen is generally well tolerated, matching findings from earlier cohorts.
4. Probability of Success: Conditional probability analyses suggest a promising outlook for achieving targeted htTKV efficacy thresholds, indicating a high success rate.

FDA Collaboration and Future Steps

In addition to the positive trial data, Regulus has made headway in regulatory discussions. In December 2024, the company had a successful End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA). Key components for advancing into a Phase 3 trial were agreed upon, which includes administering a single active dose and a placebo in a randomized scheme, as well as establishing inclusion and exclusion criteria for trial participants.

The timeline for endpoint assessments has been set, with a 12-month htTKV endpoint for potential Accelerated Approval and a 24-month eGFR endpoint for Full Approval.

Statements from the Company

Dr. Preston Klassen, President and Head of Research Development at Regulus, expressed optimism regarding these trial outcomes. He stated, "These trial results extend our understanding of the potential benefits and advantages of Regulus' approach in an area with high unmet medical needs. The data show farabursen is well tolerated and could serve as a safe treatment option for ADPKD."

Furthermore, Dr. Alan Yu from the University of Kansas Medical Center noted the promising nature of the results from Cohort 4, reinforcing the positive impact of farabursen on biomarker levels and kidney volume growth rates across multiple treatment cohorts.

Looking Ahead

CEO Jay Hagan emphasized the encouraging feedback from the FDA and the company's excitement about the next steps for farabursen in treating ADPKD. The recent updates reinforce their conviction in the drug's potential as a therapeutic option. As the company prepares to transition into pivotal studies later in the year, ADPKD patients may be on the verge of having a safer and more tolerable treatment alternative.

For those interested in further details regarding this clinical trial and its progression, additional information can be accessed at clinicaltrials.gov under the identifier NCT05521191.

In summary, Regulus Therapeutics' recent trial updates represent significant progress in the fight against ADPKD, showcasing both safety and efficacy through their innovative approach with farabursen, and holding promise for future regulatory milestones and patient outcomes.