Historically, people with amyotrophic lateral sclerosis (ALS) experience a relentless decline of neurological function that eventually robs them of the ability to move, speak, eat or breathe. Now, researchers from Washington University School of Medicine in St. Louis and collaborators report that long-term use of tofersen, a new drug approved by the Food and Drug Administration (FDA) for a genetic form of this deadly illness, delays symptom progression and death and in about one-quarter of participants leads to stabilization or improvement.
The new findings, published Dec. 22 in JAMA Neurology, provide long-term follow-up results from a phase 3 trial of tofersen and its open label extension, both co-led by WashU Medicine, that served as the basis for the FDA’s approval in 2023 of the drug for this rare form of ALS.
“Stopping disease progression and making improvements over three to five years is unheard of in this type of ALS,” said first author Timothy M. Miller, MD, PhD, the David Clayson Professor of Neurology at WashU Medicine and co-director of the WashU Medicine ALS Center. “Tofersen shows benefits compared with what we expect to see for these participants, with about 25% of participants experiencing improvement. These results provide hope that we can change the trajectory of this devastating disease, and we are optimistic we can do the same for other forms of ALS.”
Tofersen is designed to treat ALS caused by variants in a gene called SOD1, which accounts for about 2% of ALS cases. Earlier results of the phase 3 trial showed the drug reduced neurodegeneration and prompted the FDA to approve the drug in 2023 under an accelerated approval pathway. The drug, designed specifically for this type of ALS and based in part on research conducted at WashU Medicine, blocks production of the mutated SOD1 protein.
Now, new data on the long-term use of tofersen suggest that over about three years of treatment, roughly one-quarter of participants in one study group experienced stabilization of symptoms and even functional improvement in grip strength and respiratory function.