ALS gene therapy prepares to move to clinical trials in China, US
Global Phase 1/2a trial planned for both countries
China’s National Medical Products Administration has granted Sineugene Therapeutics permission to begin clinical trials of its gene therapy SNUG01 in people with amyotrophic lateral sclerosis (ALS), clearing the way for clinical trials.
The announcement follows a similar decision by the U.S. Food and Drug Administration (FDA). It sets the stage for a Phase 1/2a clinical trial evaluating the safety, optimal dosage, and potential efficacy of SNUG01 in ALS patients in both countries.
The study will take place at multiple sites, including Massachusetts General Hospital in the U.S. and Peking University Third Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, and Fujian Medical University Union Hospital in China.
“The dual clearance accelerates and validates the strategy for the development of potentially transformative therapies for people with ALS worldwide,” Merit Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and the trial’s principal investigator, said in a company press release. “We are pleased to collaborate on this study and look forward to evaluating the therapy’s potential impact on patients living with ALS.”
The FDA recently granted SNUG01 orphan drug status, a designation designed to accelerate the development of potential therapies for rare diseases by providing developers with a range of development and commercial incentives.
SNUG01 targets broad set of patients
In ALS, motor neurons — nerve cells that control voluntary movements — degenerate, leading to muscle weakness, disability, and eventually respiratory failure. Approved ALS therapies can slow disease progression and extend survival, but their benefits are limited.
SNUG01 is a first-in-class gene therapy designed to deliver the human TRIM72 gene to nerve cells. TRIM72, which encodes a protein with neuroprotective properties, was first identified as a potential therapeutic gene by researchers at Tsinghua University in China. The gene is packaged inside a modified, harmless viral vector and is administered via a one-time injection into the spinal canal.
Unlike most ALS gene therapies that target specific genetic mutations in a small subset of patients, SNUG01’s neuroprotective mechanism has the potential to benefit those with sporadic disease, which accounts for more than 90% of ALS cases, according to Sineugene.
In preclinical studies, TRIM72 production in nerve cells slowed ALS progression and extended the lifespan of ALS mice. TRIM72 also suppressed inflammation, improved membrane repair, restored the activity of energy-producing mitochondria, and reduced oxidative stress, a type of cellular damage driven by the accumulation of toxic oxidant molecules.
SNUG01 showed early signs of effectiveness and a favorable safety and tolerability profile in a now-complete investigator-initiated trial in China. In a compassionate use study (ChiCTR2400085764), SNUG01 also stabilized ALS progression in a patient whose disease had been rapidly progressing before treatment.
Another investigator-initiated trial (NCT06645197) began earlier this year to test different doses of the gene therapy in ALS patients in China.
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