Critical Takeaways, Learning Experiences From the Tofersen Trials in ALS: Timothy Miller, MD, PhD


The codirector of the ALS Center at Washington University School of Medicine provided perspective on the lessons learned from the trials of tofersen, as it aims to become the first FDA-approved therapy specific to SOD1 ALS. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"At our institution at Washington University in St. Louis, we’re beginning to think about for the group on tofersen, how to rehab ALS. These are new ideas. How do we begin to do that? We’ll continue learning. From this study, we were thrilled to get the first publication out to the community in the New England Journal of Medicine publication in September 2022."

Those within the amyotrophic lateral sclerosis (ALS) community will be tuning into the FDA’s decision on April 25, 2023, whether Biogen’s investigational agent tofersen, a drug designed to treat those with SOD1 mutations of the disease, is approved. There are currently no approved therapies for those with SOD1 ALS, and only a handful of approved therapies for ALS in general. Tofersen, an antisense oligonucleotide, had its new drug application (NDA) accepted in July 2022, with data from a phase 1 study of healthy volunteers, a phase 1/2 dose ascending study, the pivotal phase 3 VALOR study (NCT02623699) and its open-label extension, serving as the basis for the NDA.1

Recently, in September 2022, Biogen published the combined analysis of VALOR and its OLE in the New England Journal of Medicine. VALOR, a large-scale study that included 108 participants with SOD1 ALS, showcased tofersen’s impact on neurofilament light and SOD1 protein. Although it failed to meet its primary end point of statistically significant change from baseline in Revised ALS Functional Rating Scale (ALSFRS-R) after 28 weeks of treatment (difference, 1.2 points; = .97), it continued to demonstrate positive effects across multiple secondary and exploratory end points that were observed over a 12-month treatment period.2

With the potential approval looming, NeurologyLive® reached out to lead investigator Timothy Miller, MD, PhD, to get perspective on the lessons learned from tofersen. Miller, the codirector of the ALS Center at Washington University, discussed the importance of tofersen’s impact on neurofilament light, a biomarker of neuronal damage, and the advantages antisense oligonucleotides bring to the ALS field.

1. Biogen announces FDA’s 3-month extension of review period for the new drug application for tofersen. News release. Biogen. October 17, 2022. Accessed October 17, 2022.
2. Miller TM, Cudkowicz ME, Genge A, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022;387:1099-1110. doi:10.1056/NEJMoa2204705.
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