Abstract | November 18, 2023
Emerging Disease-Modifying Therapies for Amyotrophic Lateral Sclerosis
Learning Objectives
- Upon completion of this lecture, learners should be better prepared to discuss the clinical trial findings of the three FDA-approved disease-modifying therapies for ALS: Edaravone, Relyvrio, and Tofersen.
- Upon completion of this lecture, learners should be better prepared to identify the potential benefits of Edaravone, Relyvrio, and Tofersen for people with ALS.
Background/Knowledge Gap:
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to progressive muscle weakness and paralysis. There is no cure for ALS, but recent advances in understanding the genetic and molecular aspects of the disease have opened new avenues for developing disease-modifying therapies. The goal is to provide a comprehensive overview of the clinical trial findings of the three FDA-approved disease-modifying therapies for ALS: Edaravone, Relyvrio, and Tofersen. Additionally, the focus is on shedding light on the progression of these therapies from animal trials to the approval stage.
Methods/Design:
We searched for articles published from January 2010 to June 2023 (PubMed and Google Scholar) using the following keywords: ALS, disease-modifying therapy, clinical trial, and Edaravone or Relyvrio or Tofersen. We included findings from preclinical studies to randomized controlled trials – phase I, II, and III studies.
Results/Findings:
The results of the clinical trials of Edaravone, Relyvrio, and Tofersen have shown promising results in slowing the progression of ALS. Edaravone, marketed as Radicava, is an intravenous drug that reduces oxidative stress in nerve cells and slows down the decline of physical function in ALS patients. It was approved by the FDA in 2017, and an oral formulation was approved in 2022. Tofersen, marketed as Qalsody, is an antisense oligonucleotide that targets a mutation in the SOD1 gene, which causes about 2% of ALS cases. It was approved by the FDA in 2023 after showing a reduction of SOD1 protein levels and a slower rate of disease progression in SOD1-ALS patients. Relyvrio, a combination of sodium phenylbutyrate and taurursodiol, is an oral drug that prevents nerve cell death by blocking cell stress signals. It was approved by the FDA in 2022 after demonstrating a slower rate of decline on a clinical assessment of daily functioning and longer overall survival compared to a placebo in ALS patients.
Conclusion/Implications:
The results of the Edaravone, Relyvrio, and Tofersen clinical trials suggest that these therapies can potentially improve the lives of people with ALS. Further research is needed to confirm these therapies’ long-term efficacy and safety.
References and Resources
- Sun, Y., Li, X., & Bedlack, R. (2023). An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis. Expert Review of Neurotherapeutics, 23(1), 1-7.
- Johnson, S. A., Fang, T., De Marchi, F., Neel, D., Van Weehaeghe, D., Berry, J. D., & Paganoni, S. (2022). Pharmacotherapy for amyotrophic lateral sclerosis: a review of approved and upcoming agents. Drugs, 82(13), 1367-1388.
- Miller, T. M., Cudkowicz, M. E., Genge, A., Shaw, P. J., Sobue, G., Bucelli, R. C., … & Fradette, S. (2022). Trial of antisense oligonucleotide tofersen for SOD1 ALS. New England Journal of Medicine, 387(12), 1099-1110.
- Sawada, H. (2017). Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis. Expert opinion on pharmacotherapy, 18(7), 735-738.
