A newly approved drug is showing encouraging results for a small group of people living with amyotrophic lateral sclerosis, or ALS. The findings come from researchers at Washington University School of Medicine in St. Louis.
The drug, tofersen, was approved by the U.S. Food and Drug Administration in 2023. It is used to treat a rare genetic form of ALS caused by mutations in the SOD1 gene.
That genetic form accounts for about 2 percent of all ALS cases. New long-term data show the drug may slow disease progression and improve strength and mobility for some patients.
The study results were published Dec. 22 in JAMA Neurology. The data come from a phase 3 clinical trial and a long-term follow-up extension.
Researchers tracked patients for up to five years after treatment began. They found outcomes that differ sharply from the typical course of ALS.
ALS is a progressive neurological disease. It destroys nerve cells that control muscle movement, speech, swallowing, and breathing.
Most ALS patients experience steady decline. Stabilization or improvement is extremely rare.
The average life expectancy for patients with SOD1-related ALS is two to three years after symptoms begin. That makes the new findings especially notable.
Researchers reported that about one-quarter of patients receiving tofersen experienced stabilization or improvement after roughly three years. Some patients showed improved grip strength and better breathing function.
Others still experienced decline. However, their disease progressed much more slowly than expected.
“This kind of stabilization and improvement over several years is essentially unheard of in ALS,” said Dr. Timothy Miller. He is a neurologist at Washington University School of Medicine and the study’s lead author.
Miller said the results show genetic targeting can alter the disease course. He added that the findings open the door to treating other forms of ALS in the future.
Tofersen works by blocking production of the abnormal SOD1 protein. That protein damages motor neurons.
The drug is administered once a month. It is delivered by injection into the fluid surrounding the spinal cord.
One patient highlighted in the study was diagnosed in his early 40s. He reported fewer muscle spasms and improved mobility after two years on the drug.
His condition improved enough to qualify for knee replacement surgery. Doctors had previously ruled it out because his ALS was too advanced.
All patients in the trial eventually received tofersen. However, some began treatment six months earlier than others.
Patients who started the drug earlier had a significantly lower risk of death during the first six months. That risk was lower compared with those who initially received a placebo.
Over the long term, survival exceeded expectations. At least half of participants were still alive nearly five years after the study began.
Researchers said tofersen does not help everyone. Still, for patients who respond well, the benefits are substantial.
They noted the study design limits direct comparisons between early- and late-start groups. That is because all participants eventually received the drug.
The most common side effects included headaches, back pain, falls, and injection-related pain. About 9 percent of patients experienced more serious neurological side effects.
Those more serious effects were inflammatory in nature. Researchers said they were treated successfully.
The drug was developed through collaboration with Biogen and Ionis Pharmaceuticals. Biogen funded the clinical trials.
According to the Centers for Disease Control and Prevention, about 34,000 people in the United States are living with ALS. That number is expected to rise as the population ages.
Researchers are now launching a new clinical trial. It will test whether tofersen can prevent or delay ALS symptoms in people who carry SOD1 gene mutations but are not yet sick.
They say the findings suggest ALS could one day become a manageable condition. Instead of being rapidly fatal, it could be treated as a long-term disease.