• By Cara Murez HealthDay Reporter
• Posted September 23, 2022

Hints That Experimental Drug Might Curb a Form of ALS

People with a rare genetic form of ALS may benefit from extended use of an investigational drug, a new study shows.

The medication, tofersen, benefited patients with mutations of the gene SOD1. These mutations create a misfolded version of a protein, which leads to amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

In a phase 3 clinical trial, tofersen reduced molecular signs of the disease and curbed neurodegeneration, the decline and loss of nerve cell function. It did not improve movement and muscle strength at six months. But longer-term use may help stabilize muscle strength and control, the study showed.

Researchers from Washington University School of Medicine in St. Louis called that result encouraging.

"This is an exciting and hopeful step toward finding a therapy for SOD1-related ALS," said principal investigator Dr. Timothy Miller, co-director of the university's ALS Center.

Researchers saw clear evidence that the drug slows down the SOD1 mutation and the disease process.

"We didn't see substantial clinical improvement at six months, but the stabilization in function and strength at longer time points suggests it may take time for people to heal from the damage that has already been caused," Miller said in a school news release. "The vast majority of people living with ALS experience a relentlessly progressive downhill course, so the stabilization of function "¦ is truly remarkable."

About 20,000 Americans live with ALS, which is progressive and fatal. About 2% of ALS cases are caused by SOD1 mutations.

Tofersen is what is called an antisense oligonucleotide, which is a DNA-based molecule that interferes with the genetic instructions for building proteins. The molecule is designed to block production of the SOD1 protein.

The phase 3 trial included 108 ALS patients in 10 countries. About two-thirds were randomly assigned to receive eight doses of tofersen for 24 weeks. The drug was administered directly into the fluid surrounding their spinal cords.

The other third, or 36 people, received eight doses of a placebo.

At the start and again after 28 weeks, participants' were evaluated in four areas: swallowing and speaking, breathing, fine motor skills and gross motor skills. Researchers also measured levels of ALS-associated proteins in their spinal fluid.

At the end of the placebo-controlled portion of the study, participants were offered the option to continue receiving tofersen for up to 4½ years, and 95 participants decided to take advantage of this open-label extension trial.

An interim analysis of the two groups six months later found a significant difference in motor function between those who started taking tofersen at the trial's start and those who started taking it six months later when the placebo portion of the trial was done.

Some who had been on the drug for a full year saw their muscle strength and control stabilize. Researchers said that was remarkable for a disease characterized by decline.

"Most of the ongoing participants at our site have regained and/or maintained a number of their activities of daily living, and our exams and strength measurements corroborate their history of improvement, stabilization or both," said Dr. Robert Bucelli, co-director of the ALS Center.

Researchers plan to continue monitoring participants' motor function as the open-label extension continues.

Pharmaceutical company Biogen, which makes the drug, sponsored the trial.

In July, the U.S. Food and Drug Administration accepted Biogen's new drug application for tofersen as a treatment for ALS linked to SOD1 mutations.

The findings were published Sept. 22 in The New England Journal of Medicine.

Co-investigator Dr. Merit Cudkowicz said the results offer the ALS community great hope for treatments that can slow or stop disease progression.

"The drug has the potential to improve the quality of life for people living with SOD1-ALS by stabilizing muscle function with longer-term use, which is an extremely promising development," said Cudkowicz, director of the Sean M. Healey & AMG Center for ALS in Boston.

Though these trial results apply to only to ALS patients with SOD1 mutation, the authors said this research could inform other work that may benefit folks with other forms of the disease.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more on ALS.

SOURCE: Washington University School of Medicine in St. Louis, news release, Sept. 21, 2022