China-based Ractigen Therapeutics reported Phase I data from its RAG-17 program in SOD1-mutated amyotrophic lateral sclerosis (ALS) showing an 81.2% reduction in plasma neurofilament light chain from a single intrathecal dose, alongside a clean safety profile across all five dose cohorts tested.
The Phase I/II trial (NCT06556394) is a randomized, double-blind, placebo-controlled single ascending dose study that enrolled 20 participants across five sequential cohorts (30, 90, 120, 150, and 180 mg) at a 3:1 active-to-placebo ratio.
In the 150 mg cohort, CSF SOD1 protein fell by 58.1% from baseline by Day 90, with reductions persisting through Day 210 — the longest follow-up reported. In the 180 mg cohort, plasma neurofilament light chain dropped 81.2% by Day 150. Functional data from the same cohort, assessed by ALSFRS-R, showed zero decline at Day 90 in the three evaluable participants, with minimal decreases (0 to 4 points) at Day 150. All results were presented under blinded analysis, as the study remains ongoing. No serious adverse events or Grade 3 treatment-emergent adverse events were reported; three mild treatment-related adverse events occurred across all cohorts.
RAG-17 is a siRNA designed to silence SOD1 mRNA, delivered intrathecally via Ractigen's proprietary SCAD platform, which conjugates the siRNA duplex to an accessory oligonucleotide to facilitate CNS distribution. The durability of SOD1 suppression through Day 210 from a single dose is the central mechanistic claim: if confirmed in larger, unblinded cohorts, it would distinguish RAG-17 from tofersen (Qalsody), the antisense oligonucleotide approved by the US FDA in 2023 for SOD1-ALS, which requires monthly intrathecal maintenance dosing. Cross-trial comparisons are limited by differences in study design, patient populations, and blinding status, and the current RAG-17 data derive from very small subgroups. The ALSFRS-R observations in particular — drawn from three participants in one dose cohort — cannot support efficacy conclusions at this stage.
Ractigen said a Phase II multiple ascending dose study began dosing on January 13, 2026, with enrollment completed in two cohorts. The Phase II trial is randomized, double-blind, and placebo-controlled, and is designed to evaluate repeated intrathecal injections in SOD1-mutation carriers across multiple sites in China.
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