Understanding Tofersen’s Impact on SOD1 ALS, Neurofilament Light: Timothy Miller, MD, PhD


The codirector of the ALS Center at Washington University School of Medicine in St. Louis discussed the long-term data of VALOR and its open-label extension assessing tofersen (Biogen) in SOD1 ALS. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"The first [important finding] is that the levels of SOD1—the protein that we’re targeting—were lowered in the cerebrospinal fluid of the participants that were treated with the drug. This is good news. It shows the drug is doing exactly what it’s supposed to do."

There has been a palpable buzz within the amyotrophic lateral sclerosis (ALS) field as of recent, with the approval of AMX035 (Relyvrio; Amylyx Pharmaceuticals) in September and the potential approval of tofersen (Biogen), an agent in development for SOD1-mutated ALS, in the coming spring. The antisense oligonucleotide had its new drug application 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 (OLE), serving as the basis for the NDA.1

In VALOR, 108 patients with SOD1-mutated ALS were randomized to tofersen 100 mg (n = 72) or placebo (n = 36) and treated for a 28-week treatment period. The combined analysis at week 52 of VALOR and its OLE was prespecified and intended to enable the comparison of early-start and delayed-start tofersen in the full intention-to-treat population. Another analysis has been planned when all participants have completed at least 3.5 years of follow-up, which has not yet been reached.2

At the 2022 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, held November 1-3, in Clearwater Beach, Florida, principal investigator Timothy Miller, MD, PhD, presented additional data from VALOR and its OLE. Miller, the codirector of the ALS Center at Washington University School of Medicine in St. Louis, sat down with NeurologyLive® to provide insight on the data neurologists should key in on. Specifically, he discussed tofersen’s impact on SOD1 protein and neurofilament light, as well as the need to initiate treatment as early as possible after ALS diagnosis.

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. https://www.globenewswire.com/news-release/2022/10/17/2535365/0/en/Biogen-Announces-FDA-s-3-Month-Extension-of-Review-Period-for-the-New-Drug-Application-for-Tofersen.html
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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