Therapeutics Company Reports Positive Topline Data From Major Clinical Trial
Positive Topline Data from Regulus Therapeutics' Phase 1b MAD Clinical Trial of RGLS8429 for ADPKD.
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Regulus Therapeutics Inc., a biopharmaceutical company listed on Nasdaq under the ticker symbol RGLS, has recently announced positive topline results from the third cohort of patients in its Phase 1b Multiple-Ascending Dose (MAD) clinical trial of RGLS8429. This investigational drug is being developed for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic disorder characterized by the growth of numerous cysts in the kidneys.
Overview of the Phase 1b MAD Study
The Phase 1b MAD study is designed as a double-blind, placebo-controlled trial to assess multiple parameters of RGLS8429, including its safety, tolerability, pharmacokinetics (how the drug is absorbed, distributed, metabolized, and excreted in the body), and pharmacodynamics (the effects of the drug on the body). The trial focuses on adult patients diagnosed with ADPKD and evaluates the drug across three different weight-based dose levels and one fixed dose level.
Key parameters measured in the study include changes in urinary polycystins 1 and 2 (PC1 and PC2), total kidney volume (htTKV), cyst architecture, and overall kidney function. PC1 and PC2 are protein products of the PKD1 and PKD2 genes, respectively, and their levels have been shown to inversely correlate with the severity of ADPKD. The study aims to provide a comprehensive understanding of how RGLS8429 affects these critical biomarkers.
In the third cohort of the study, 16 subjects were randomized in a 3:1 ratio to receive either 3 mg/kg of RGLS8429 or a placebo every other week for three months. The results from this cohort were promising:
Safety and Tolerability: RGLS8429 was well tolerated by the participants, with no notable safety concerns identified during the trial.
Mechanistic Dose Response: There was continued evidence of a dose response based on urinary PC1 and PC2 levels. The 3 mg/kg dose demonstrated more consistent increases in these biomarkers compared to earlier cohorts.
Statistical Significance: Percent change from baseline in PC1 and PC2 showed a dose response across all doses tested, with statistical significance achieved at the 3 mg/kg dose compared to the placebo group.
Imaging Biomarkers: Exploratory MRI imaging analysis suggested that RGLS8429 reduced htTKV at the 3 mg/kg dose after three months of dosing. Remarkably, 70% of subjects demonstrated reductions in htTKV at this dose level.
Dr. Preston Klassen, President and Head of Research & Development at Regulus Therapeutics, expressed satisfaction with the consistent mechanistic response and reduction in htTKV observed at the 3 mg/kg dose level. He highlighted the appropriate safety and tolerability profile of RGLS8429, which lends support to the ongoing and final 300 mg fixed dose cohort in this Phase 1b trial.
Moving Forward: The Fourth Cohort
Following the positive results from the third cohort, enrollment has been initiated for the fourth cohort of the trial. This cohort will include up to 30 patients who will receive an open-label fixed dose of 300 mg of RGLS8429 every other week for three months. In addition to evaluating PC1 and PC2 levels and safety, this cohort will also assess imaging biomarkers to provide further insights into the drug's efficacy.
Jay Hagan, CEO of Regulus Therapeutics, reiterated the importance of the results from the third cohort, particularly the reduction in htTKV observed in the majority of patients. These findings bolster confidence in RGLS8429's potential to address the underlying genetic cause of ADPKD. He emphasized that the data from this study will form the basis for a potentially pivotal Phase 2/3 study of RGLS8429 under an Accelerated Approval regulatory pathway, which will be discussed with the FDA.
Understanding ADPKD and the Role of RGLS8429
ADPKD is a common genetic disorder that affects approximately 1 in 1,000 people worldwide. It is characterized by the development of numerous fluid-filled cysts in the kidneys, leading to progressive enlargement of the kidneys and decline in kidney function over time. The disease is caused by mutations in the PKD1 and PKD2 genes, which encode for the proteins polycystin-1 (PC1) and polycystin-2 (PC2).
These proteins play crucial roles in the regulation of cell growth, differentiation, and apoptosis (programmed cell death). Mutations in PKD1 or PKD2 result in aberrant signaling pathways, leading to cyst formation and growth. As the cysts enlarge, they compress the surrounding kidney tissue, obstructing normal kidney function and ultimately leading to kidney failure in many patients.
RGLS8429 is an innovative therapeutic approach that targets microRNAs, small non-coding RNAs that regulate gene expression. By modulating the expression of specific microRNAs associated with the PKD1 and PKD2 genes, RGLS8429 aims to restore normal cellular processes and reduce cyst growth. The promising results from the Phase 1b MAD study suggest that this approach may hold potential for effectively managing ADPKD.
Conclusion
The positive topline data from the third cohort of Regulus Therapeutics' Phase 1b MAD clinical trial of RGLS8429 for the treatment of ADPKD represents an important step forward in the development of a novel therapeutic option for this challenging genetic disorder. The consistent mechanistic response, reduction in htTKV, and appropriate safety and tolerability profile observed at the 3 mg/kg dose level provide a strong foundation for further clinical development.
The initiation of the fourth cohort, which will evaluate a 300 mg fixed dose of RGLS8429, marks the next phase of this important research. As Regulus Therapeutics continues to advance its clinical program, there is optimism that RGLS8429 could become a valuable treatment option for patients living with ADPKD.
Disclaimer: The information provided in this article is for educational purposes only and should not be construed as medical or investment advice. Please consult with a healthcare professional or financial advisor for personalized guidance.
Real-time information is available daily at https://stockregion.net