8-K: Regulus Therapeutics Announces Positive Topline Results from Phase 1b Study of Farabursen for ADPKD

Regulus Therapeutics reports positive topline results from the fourth cohort of its Phase 1b study of farabursen (RGLS8429) for autosomal dominant polycystic kidney disease (ADPKD), showing a halting of kidney volume growth.

Summary

• Regulus Therapeutics announced positive topline results from the fourth cohort of patients in its Phase 1b multiple-ascending dose (MAD) study of farabursen (RGLS8429) for the treatment of autosomal dominant polycystic kidney disease (ADPKD).
• In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months.
• The full cohort of 26 patients demonstrated a similar mechanistic response based on urinary PC1 and PC2 levels as well as a mean halting of htTKV growth over the four-month study period, consistent with the previously announced interim analysis.
• Mean htTKV growth rate over 4 months was 0.05% (SE -0.86% to +0.92%) in the farabursen group, while placebo subjects experienced a mean growth rate of 2.58% (SE +1.09% to +4.10%).
• Changes in htTKV were highly correlated with changes in renal cyst volume, suggesting farabursen directly impacts disease progression by limiting abnormal cyst growth.
• An exploratory analysis comparing patients treated with 3 mg/kg or 300 mg fixed dose farabursen (n=35) to a combined historical control group of placebo-treated patients (n=550) showed that farabursen-treated patients experienced a mean reduction in htTKV growth rate (-0.14%) compared to a mean increase of (+1.87%) in placebo-treated patients (p=0.0056).
• Farabursen at 300 mg demonstrated a favorable safety and tolerability profile in this study, consistent with earlier cohorts.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results, indicating potential for a new treatment for ADPKD. The favorable safety profile and statistically significant reduction in kidney volume growth contribute to a positive outlook.

Positives

• The Phase 1b study showed positive topline results for farabursen in treating ADPKD.
• Farabursen demonstrated a favorable safety and tolerability profile.
• The 300 mg fixed dose of farabursen led to a mean halting of htTKV growth.
• The study showed statistically significant results in reducing htTKV growth rate compared to historical placebo data (p=0.0056).
• Increases in urinary PC1 and PC2 levels were similar to cohort 3 and reached a similar level of statistical significance compared to placebo (PC1 p=0.026; PC2 p=0.014).

Risks

• The forward-looking statements are subject to risks and uncertainties, and actual results may differ materially.
• The approach to discover and develop drugs is novel and may never lead to marketable products.
• Preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and may not be indicative of future results.
• An accelerated approval pathway designation may not be received, or even if it is received, lead to a faster development, regulatory review or approval process, and does not increase the likelihood that farabursen will receive marketing approval.
• Clinical studies may not be successful.
• There are risks related to regulatory review and approval.
• There are risks related to reliance on third-party collaborators and other third parties.
• There are risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics.
• Additional data may be negative.
• There are risks related to the ability to successfully secure and deploy capital.

Future Outlook

Regulus plans to advance farabursen into a pivotal study in the third quarter of 2025 and believes it has the potential to be a safe and effective treatment option for ADPKD.

Industry Context

This announcement is significant in the context of ADPKD treatment, as it addresses the underlying genetic causes of the disease and shows potential for halting kidney volume growth, a key indicator of disease progression. The results could position farabursen as a competitive therapy in the ADPKD market.

Comparison to Industry Standards

• The document references the TEMPO 3:4 trial and the STAGED-PKD trial as part of the historical placebo group, indicating that these are relevant benchmarks in the ADPKD field.
• The efficacy of currently-approved therapy is mentioned as a 50% reduction in TKV progression, providing a benchmark for comparison.

Stakeholder Impact

• Shareholders may react positively to the promising clinical trial results.
• Patients with ADPKD may benefit from a new potential treatment option.
• The company's employees may be motivated by the progress in drug development.

Next Steps

• Advancing farabursen into a pivotal Phase 3 study in the third quarter of 2025.

Key Dates

Keywords

farabursen, RGLS8429, ADPKD, autosomal dominant polycystic kidney disease, htTKV, Phase 1b study, Regulus Therapeutics, clinical trial, kidney disease, therapeutics