FDA Grants Orphan Drug Designation to RAG-21 for ALS Treatment

FDA Grants Orphan Drug Designation to RAG-21 for ALS Treatment

The FDA has granted orphan drug designation to RAG-21, a new therapy from Ractigen Therapeutics, for treating amyotrophic lateral sclerosis (ALS). Preclinical studies show that RAG-21 may reduce motor neuron degeneration and improve outcomes for ALS patients.

ALS is a serious neurodegenerative disease. It significantly affects patients’ quality of life and currently has no cure. Most patients face respiratory failure within 2 to 5 years after diagnosis. Experts link mutations in the FUS gene to a severe form of ALS, marked by early onset and rapid progression. These mutations can cause toxic protein accumulation and neuron damage, leading to motor neuron degeneration.

RAG-21 is a small interfering RNA (siRNA) treatment aimed at FUS-ALS, one of the most aggressive ALS types. It uses RNA interference to lower FUS mRNA transcripts. This process stops the production of harmful FUS proteins, tackling the disease’s root cause. RAG-21 offers targeted and effective gene knockdown within the central nervous system.

“The FDA’s orphan drug designation for RAG-21 highlights the urgent need for treatments targeting ALS, especially for patients with FUS mutations,” said Long-Cheng Li, MD, founder and CEO of Ractigen Therapeutics. He emphasized that FUS-ALS has no available curative treatments. The company aims to develop innovative therapies like RAG-21 to give ALS patients and those with other rare diseases meaningful options.

RAG-21 has similarities to RAG-17, another Ractigen Therapeutics drug targeting SOD1 mutations associated with ALS. The FDA granted RAG-17 an orphan drug designation in March 2023. Both therapies share the same delivery method and initial studies of RAG-17 show positive results regarding safety and tolerability.

In the RAG-17 trial, six patients with SOD1-mutation ALS received doses starting at 60 mg intrathecally. They were monitored for side effects before increasing their dose every 30 mg or 14 days. The results showed RAG-17 was well-tolerated, with only mild side effects reported. Detailed evaluations also supported a positive safety profile.

Initial signs of clinical benefit were noted, with meaningful changes in clinical outcomes and key biomarkers suggesting efficacy for patients with SOD1-mutation ALS. Further results will be shared at the 2024 International Symposium on ALS/MND in Montreal, Canada, from December 6 to 8. These findings align with preclinical data indicating significant therapeutic effects in animal models, including delayed progression of the disease and improved survival rates.

“These initial clinical results are encouraging and bring us closer to providing hope for ALS patients,” said Li. He added that the promising outcomes suggest RAG-17 could serve as a disease-modifying therapy for ALS-SOD1.