1st patient dosed in Phase 2 trial of SOD1-ALS treatment RAG-17
Study enrolling in China following successful Phase 1 trial
- RAG-17, an siRNA therapy, is in Phase 2 trials for SOD1-ALS.
- It targets SOD1 gene mutations, reducing toxic protein levels.
- Phase 1 showed RAG-17 was safe and slowed functional decline.
The first patient has been dosed in a Phase 2 clinical study testing RAG-17, a therapy being developed by Ractigen Therapeutics for people with amyotrophic lateral sclerosis (ALS) who carry mutations in the SOD1 gene (SOD1-ALS).
The progression into the Phase 2 portion of the trial follows the successful completion of a Phase 1 trial (NCT06556394), which demonstrated that a single injection of RAG-17 was safe at multiple dose levels and showed promising signs of efficacy.
The Phase 2 trial will test multiple ascending doses of the investigational therapy against a placebo to continue evaluating its safety, tolerability, and pharmacological properties.
The initial dosing was performed at Second Affiliated Hospital, Zhejiang University School of Medicine in China. Enrollment is also ongoing at four additional clinical sites in China.
“The successful dosing of the first patient represents a significant milestone in our mission to develop transformative therapies for ALS,” Long-Cheng Li, MD, Ractigen’s founder and CEO, said in a company press release. “The positive results from the Phase I trial affirm the promise of RAG-17 and provide us with strong confidence in its potential to markedly improve the lives of patients suffering from SOD1-mutated ALS.”
siRNA aims to reduce protein levels
ALS is caused by the progressive loss of motor neurons, the nerve cells that control voluntary movements. Mutations in the SOD1 gene, which result in the production of an abnormal SOD1 protein, are associated with up to 20% of familial ALS cases and about 2% of those with sporadic disease.
The SOD1 protein has antioxidant properties. Mutations in its gene, however, lead to the production of an abnormal protein that is unable to effectively neutralize toxic oxygen-containing molecules and is prone to form toxic clumps that contribute to nerve cell damage in ALS.
RAG-17 is a small interfering RNA, or siRNA, designed to reduce levels of abnormal SOD1. It works by binding to SOD1′s messenger RNA, the intermediate molecule that serves as a template for protein production, targeting it for destruction. This prevents production of the harmful protein.
The treatment is given via injections into the spinal canal (intrathecal injection).
An investigator-initiated Phase 1 trial (NCT05903690), conducted at a single center in China, tested RAG-17 in six adults with SOD1-ALS. The therapy was given every two months for up to eight months, after adjusting treatment until an optimal dose was determined.
Data showed that RAG-17 was well tolerated at all tested doses, reduced SOD1 levels in the spinal fluid, and lowered blood levels of neurofilament light chain (NfL), a marker of nerve cell death. Findings also suggested that the treatment slowed functional decline and stabilized lung function.
While this trial was underway, Ractigen began a Phase 1/2 trial. In the Phase 1 portion, approximately 32 people with SOD1-ALS were randomly assigned to receive a single injection of either RAG-17 or a placebo, in addition to standard ALS therapies.
The company said the move to Phase 2 follows “highly encouraging data” from Phase 1, in which RAG-17 demonstrated an “exceptional safety profile.” A single injection of the therapy also led to significant reductions in spinal fluid SOD1 and blood NfL levels.
“We are excited to be part of this important study,” said the trial’s leader, Zhi-Ying Wu, MD, PhD, a professor at Zhejiang University School of Medicine. “Based on the improvements we have observed clinically, we look forward to further investigating RAG-17’s potential to enhance the quality of life for ALS patients as we progress.”
RAG-17 has received orphan drug designation from the U.S. Food and Drug Administration. The status provides incentives to support the development of treatments for rare and serious diseases.
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