Future Role of Neurofilament Light in ALS Drug Development, Clinical Trials: Rita Sattler, PhD, MSc

WATCH TIME: 3 minutes

"The mechanisms of what happens with neurofilament when it's released into those bioflow is not yet quite understood. We tend to think it's because of the destruction of the axonal structure and the integrity of the neuron that we see an elevation of neurofilament as a consequence, but there are a lot of ideas and thoughts that an increased expression of neurofilament could also be sort of protective mechanism of the cells as a response to the stress and the pathology that the neurons undergo."

Over the last 25 years, the field of biomarker detection for patients with amyotrophic lateral sclerosis (ALS) has grown exponentially, capped off by the most recent approval of tofersen, the first agent specific for patients with SOD1-mutated mediated ALS. Tofersen, an antisense oligonucleotide, was approved based on reductions in a surrogate biomarker of neurofilament light (NfL). In the FDA’s decision, they determined that the use of this neuroaxonal biomarker would be “reasonably likely to predict clinical benefit."

Prior to tofersen, the FDA also approved AMX0035 (Relyvrio; Amylyx Pharmaceuticals), a combination of sodium phenylbutyrate/taurursodiol, as a therapy for patients with sporadic forms of the disease. Between the 2 agents, AMX0035 was the only one to meet its primary end point of change in ALS Functional Rating Scale-Revised, a standard measure for ALS trials. In the weeks leading up to the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 3-6, in Orlando, Florida, NeurologyLive® sat down with track chair Lisa Sattler, PhD, MSc, to discuss the role of NfL as a valuable biomarker for ALS and the implications of tofersen’s approval.

Sattler, a professor in the Department of Translational Neuroscience at Barrow Neurological Institute, provided commentary on the advantages of NfL as well as the questions that remain with its use in clinical practice and trial settings. She stressed that although it may be a significant biomarker for this patient population, treating the disease effectively will come through a combination approach of various targets.

Registration for the 2024 MDA Conference is now open! The meeting is set to be held at the Hilton Orlando, in Orlando, Florida, from March 3 to 6, 2024. To register and for more information, head to www.mdaconference.org