ALS Update: Drug Therapy Continues to Offer Little Benefit

SAVANNAH, GEORGIA — Current disease-modifying therapies for amyotrophic lateral sclerosis (ALS) don’t extend lifespans by much, but several drug options are available, nerve specialists learned.
The glutamate blocker riluzole (Rilutek), which became the first ALS drug to receive US Food and Drug Administration (FDA) approval in 1995, continues to be used, said Michael D. Weiss, MD, professor of neurology at University of Washington School of Medicine, Seattle, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Weiss highlighted a 2012 Cochrane Library review that examined research and found the drug is “reasonably safe” and prolongs median survival by about 2-3 months. “About 12% develop liver disease. It’s pretty rare that we stop the medicine due to liver toxicity.”
Earlier Treatment Could Pay Dividends
A recent study “suggests we might be able to get more bang for our buck from riluzole” by initiating treatment earlier, Weiss said.
Researchers tracked 4778 patients with ALS, including 3446 (72.1%) who took riluzole. Those who took the drug survived a median two extra months (22.6 vs 20.2 months; P < .001). The data suggested that delaying riluzole initiation by 1 year (from 6 months to 18 months after diagnosis) reduced the median survival by 1.9 months (from 40.1 to 38.2 months).
There’s “a relatively significant additional benefit” to earlier treatment, Weiss said, although patients will vary on whether they think it’s meaningful. As for limitations, “there’s no clear impact on disease progression, and there’s a need for periodic monitoring of liver function profile.” 
He added that there’s an out-of-pocket co-pay. “Even as a generic, it’s not that cheap. Depending on the source, it could cost anywhere from $1800 to $8400 a year.”
Edaravone Could Lack Relevant Benefit
No other ALS treatment appeared until 2017, when the FDA approved the novel antioxidant edaravone (Radicava). In 2022, the agency approved an oral suspension version, but a study published that year suggested there may not be a clinically relevant benefit.
The University of Washington, where Weiss works, offered the drug to 144 patients, according to an analysis. Eighty percent of the patients wanted it, but insurers refused to cover it for more than 20%. The average time to treatment with the drug was 28 days after patients said they wanted it.
That’s a “substantial delay,” Weiss said.
The cost is about $171,000 a year, he said, and there’s no assistance for underinsured patients.
Other Options
As Weiss noted, another drug, AMX0035 (Relyvrio), received FDA approval in 2022, but its manufacturer pulled it from the US/Canada market in April 2024 following poor phase 3 trial findings.
In 2023, the FDA approved another drug, the antisense oligonucleotide tofersen (Qalsody), in patients with ALS associated with a mutation in the superoxide dismutase 1 gene. According to the FDA, reductions in plasma neurofilament light concentration were “reasonably likely to predict a clinical benefit in patients.”
Only 1%-2% of patients with ALS fit the criteria to get the drug, Weiss said. He noted other limitations such as the cost ($180,000 a year), the need for lifelong monthly intrathecal injections, and serious neurological side effects in 7% of patients per a 2022 trial.
Weiss disclosed advisory board (Alexion, Ra [now UCB], argenx, Biogen, Mitsubishi Tanabe Pharma, Amylyx), data safety monitoring board (Sanofi, AI), consulting (Cytokinetics, CSL Behring), and speaker (Soleo) relationships.
 
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