Tofersen for SOD1 ALS

• Amyotrophic lateral sclerosis, or ALS, is a devastating motor neuron disease affecting muscle function. Worldwide, thousands are diagnosed with ALS each year, and most die from lung failure within five years of symptom onset.

• In 2022, the results of a phase-three clinical trial of the drug tofersen for people with SOD1 ALS were published. Across multiple metrics, the early-start cohort fared markedly better than the delayed-start cohort, especially in the open-label extension of the trial. Notably, the drug increased survival.

• As of Sep 2022, tofersen is under priority review by the FDA, and is available under an expanded-access program.

• Dive deeper in this article on Medium.

• NIH ALS factsheet (as of 2022-09-25).

• Xu L, Liu T, Liu L, Yao X, Chen L, Fan D, Zhan S, Wang S. Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol 267:4 (2020-Apr), pp. 944-953. Online: 2019-12-03. DOI: 10.1007/s00415-019-09652-y. PMID: 31797084.

• Berdyński M, Miszta P, Safranow K, et al. SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity. Sci Rep 12, #103 (2022-Jan). DOI: 10.1038/s41598-021-03891-8. PMID: 34996976.

• GeneCards, SOD1 (as of 2022-09-25).

• Structure of the SOD1 protein by Emw. Wikimedia, 2009-12-15 (as of 2022-11-01).

• Bunton-Stasyshyn RKA, Saccon RA, Fratta P, Fisher EMC. SOD1 function and its implications for amyotrophic lateral sclerosis pathology: new and renascent themes. The Neuroscientist 21:5 (2015-Oct), pp. 519-529. Online: 2014-12-09. DOI: 10.1177/1073858414561795. PMID: 25492944.

• ALS association: Tofersen (as of 2022-09-25).

• Benkler C, O’Neil AL, Slepian S, et al. Aggregated SOD1 causes selective death of cultured human motor neurons. Sci Rep 8, #16393 (2018-Nov). DOI: 10.1038/s41598-018-34759-z. PMID: 30401824.

• ALZFORUM: Tofersen (as of 2022-09-23).

• Miller TM, Cudkowicz ME, Genge A, et al, for the VALOR and OLE working group. Trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med 387:12 (2022-Sep), pp. 1099-1110. DOI: 10.1056/NEJMoa2204705. PMID: 36129998.

• Script: R. Andreev

• Copy-edit: M. Amand, E. Myers

• Narration: Z. Forrester

• Storyboard: RA, M. Jasorka

• Animation: E. Stepsys

This animation is produced by Randompile, independently of the clinical trial or its sponsors. While we take scientific accuracy seriously, this is not medical advice; please consult your trusted physician.