ALS Association Funded Antisense Technology Behind Tofersen 

Washington, D.C. (April 25. 2023) – The ALS Association commends the FDA for approving tofersen under the agency’s accelerated approval pathway for the treatment of people living with ALS connected to mutations in the SOD1 gene. This marks the first time the FDA has approved a treatment for ALS under accelerated approval and serves as a promising endorsement of the antisense technology that underlies tofersen. 

“Every opportunity to make a new treatment available that can stop or slow down this disease is a win for the whole community,” said Larry Falivena, a member of The ALS Association’s Board of Trustees who is living with SOD1-ALS and who has participated in the tofersen trials.  

The FDA’s Central and Peripheral Nervous System Drugs Advisory Committee voted unanimously in March to support accelerated approval of tofersen.  

“The FDA’s decision marks a significant step in our effort to make ALS livable for everyone, everywhere, until we can cure it,” said Calaneet Balas, president and CEO of The ALS Association. “This is the second time in less than a year our community gets to celebrate the approval of a new drug to treat ALS and we have great hope for the future of antisense technology.”  

Tofersen is the third drug approved to treat ALS in the last six years.  

Balas added: “We thank the FDA and Biogen for working together to bring tofersen to people living with ALS as quickly as possible.” 

Tofersen is an antisense oligonucleotide therapy, a small string of DNA letters that are designed to bind to specific molecules of RNA and stop the production of toxic proteins. Tofersen was developed to specifically target the RNA produced from mutated a SOD1 gene to stop toxic SOD1 proteins from being made.  

Mutations in the SOD1 gene are found in about 10-20 percent of cases of familial ALS, as well as 1-2 percent of sporadic ALS cases.  

In approving the first antisense oligonucleotide for the treatment of ALS, the FDA also created hope for other antisense therapies currently in development to treat other forms of ALS.  

Antisense technology stems from very long investments made by The ALS Association, the NIH, and the companies IONIS and Biogen. Tofersen is a direct result of the donations from supporters of the ALS Association, the strong advocacy work of the ALS community, the scientists and clinicians carrying out this work, and most importantly, the many people living with ALS who volunteered to participate in this research.  

Approval of tofersen also shows promise for the use of secondary, or surrogate endpoints to show effectiveness of a treatment for ALS. Tofersen effectively reduced the production of a chemical known as neurofilament light (NfL) in the blood and spinal fluid. High levels of NfL are indicators of damage to motor neurons.  

The FDA’s advisory committee found that the neurofilament light levels indicate a change in the course of disease for people receiving the treatment which translates into benefits such as longer life, increased muscle function and reduced disease progression -- some months after neurofilament levels go down. 

Tofersen is currently being tested in clinical trials to determine whether it can be effective in preventing the onset of ALS in people with SOD1 mutations.  

“Tofersen could be the opportunity to break the cycle of genetic ALS for families who have been devastated by ALS for generations,” Falivena said.  

ABOUT ALS 

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Over the course of the disease, people lose the ability to move, to speak, and eventually, to breathe. On average, it takes about a year before a final ALS diagnosis is made. The disease is always fatal, usually within five years of diagnosis. There is no cure.  

ABOUT THE ALS ASSOCIATION  

The ALS Association is the largest philanthropic funder of ALS research in the world. The Association funds global research collaborations, assists people with ALS and their families through its nationwide network of care and certified clinical care centers, and advocates for better public policies for people with ALS. The ALS Association is working to make ALS a livable disease while urgently searching for new treatments and a cure. For more information about The ALS Association, visit our website at www.als.org