Ractigen Therapeutics has commenced a Phase I clinical trial of RAG-17, a small interfering RNA (siRNA) therapy designed to treat amyotrophic lateral sclerosis (ALS) associated with mutations in the superoxide dismutase 1 (SOD1) gene. The first patient was dosed at the Second Affiliated Hospital of Zhejiang University School of Medicine.
The Phase I trial is a randomized, double-blind, placebo-controlled study. It aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RAG-17 in patients with SOD1-ALS. Dr. Yilong Wang from Beijing Tiantan Hospital of Capital Medical University, Dr. Zhiying Wu from the Second Affiliated Hospital, and Dr. Huifang Shang from West China Hospital of Sichuan University are leading the trial.
RAG-17: Targeting SOD1 in ALS
RAG-17 is designed to suppress the SOD1 gene in ALS patients with pathogenic mutations. It utilizes Ractigen's Smart Chemistry Aided Delivery (SCAD) platform, which enhances the delivery of duplex RNA, such as siRNA, into the central nervous system (CNS) via intrathecal injection. Preclinical studies, including those using the hSOD1G93A mouse model, have demonstrated that RAG-17 can improve motor function and extend survival.
Clinical and Regulatory Milestones
In March 2023, the U.S. Food and Drug Administration (FDA) granted RAG-17 Orphan Drug Designation (ODD), followed by clearance of its Investigational New Drug (IND) application. In May 2024, the IND was approved by China National Medical Products Administration (NMPA)’s Center for Drug Evaluation (CDE). An Investigator-Initiated Trial (IIT) of RAG-17 showed promising clinical data, indicating that intrathecally administered RAG-17 was well-tolerated across all dose levels, with only mild adverse events reported. These findings were presented at the 27th National Conference of Neurology, Neuroscience 2024, and the 35th International Symposium on ALS/MND.
ALS and the Need for New Therapies
ALS is a severe neurodegenerative disease with no cure, characterized by muscle cramps, twitching, and weakness that progress to difficulties with movement and speech, the need for assisted breathing, paralysis, and ultimately death. Mutations in the SOD1 gene account for approximately 20% of familial ALS and 5% of sporadic ALS cases. Current treatments offer limited relief, underscoring the urgent need for innovative therapies.
Executive Perspective
"The first patient dosed in the RAG-17 trial marks a pivotal milestone in our mission to combat ALS, one of the most devastating neurodegenerative diseases," said Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics. "This achievement underscores our unwavering commitment to advancing RNA-based therapies that have the potential to transform the lives of patients and families affected by rare and severe conditions like ALS."
