FDA grants accelerated approval for ALS treatment tofersen by Biogen

Boston- The Federal Drug Administration has approved the use of tofersen, based on its effect reducing neurofilament. Tofersen is a targeted therapy aimed at slowing the progression of ALS in the subset of people with a mutation in the SOD1 gene. 

ALS is a serious uncommon neurodegenerative disease caused primarily by loss of motor neurons, resulting progressive weakness. Mutations in the SOD1 gene are responsible for approximately two percent of all ALS diagnoses. Tofersen is an antisense oligonucleotide (ASO) to SOD1 that reduces the mutated protein and ameliorates the disease. 

Tofersen was tested in the VALOR trial, a double-blind, randomized, placebo-controlled clinical trial of the effect of tofersen in people with SOD1 ALS. The trial was led by Dr. Timothy Miller of Washington University School of Medicine in St. Louis. Dr. Merit Cudkowicz, Chief of Neurology and Director of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, served as Co-Principal Investigator and has been a critical member of its clinical development. 

While the VALOR trial did not meet its primary endpoint, it showed definitively that SOD1 protein was reduced in the spinal fluid of people receiving the active study drug. Furthermore, neurofilament, a marker of neuronal death, was reduced in participants receiving tofersen. The primary endpoint and all secondary clinical endpoints trended in favor of tofersen. In addition, data from the open label extension of the trial showed more benefit in people receiving tofersen earlier compared to those randomized to receive placebo initially.

“This is a huge step forward in the fight against ALS as it will bring critical treatment options to families facing SOD1 ALS. We are incredibly proud to have been a part of the development of this drug and look forward to all the benefit it will bring,” said Dr. Cudkowicz.

The Sean M. Healey and AMG Center for ALS is recognized as a global leading institution for ALS research and care, and investigators at Mass General have been leaders in the development of tofersen. In 1994, Dr. Robert Brown led a team of researchers discovering that mutations in SOD1 caused a subset of ALS. Over the past decade, MGH researchers have taken lead roles in the development program that led to the recommendation from the advisory panel that the FDA approve tofersen for the treatment of SOD1 ALS. Dr. Suma Babu was the Principal Investigator for the Mass General trial site and has treated many people with SOD1 ALS in the trial and subsequent expanded access program. Dr. James Berry has acted as an advisor to Ionis and Biogen and Co-Investigator at Mass General.  And Jennifer Scalia, Sarah Luppino, Danica Sanders, Alex McCaffrey, Pravin Pant and Darlene Sawicki, our MGH nurses and nurse practitioners, have held key roles in the trial at MGH.

“As providers treating people with ALS, rarely have we seen a treatment that resulted not only in clear slowing of ALS progression, but in some cases, clear halting of clinical decline. We want to thank the many participants and families that have dedicated their lives to trial participation and have made this success possible,” said Dr. Babu. 

Background on ALS
Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy. There are currently few FDA therapies approved for treating ALS—riluzole, edaravone (IV and oral formulation), Nuedexta, and Relyvrio.

 About the Sean M. Healey & AMG Center for ALS at Mass General
At the Sean M. Healey & AMG Center for ALS at Mass General, we are on a quest to discover life-saving therapies for all individuals affected by ALS. Launched in November 2018, the Healey Center leverages a global network of scientists, physicians, nurses, caregivers, people with ALS and families working together to accelerate the pace of ALS therapy discovery and development.

Under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, we are reimagining how to develop and test the most effective therapies to treat the disease, identify cures and, ultimately, prevent it.

The key to our success is our tightly integrated research and clinical efforts, encouraging opportunities to bring the challenges our patients face every day into our laboratories, focusing investigations on finding solutions that will make a meaningful difference to our patients without delay. Our collaborative efforts are designing more efficient and effective clinical trials while broadening access to these trials for people with ALS.