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Comments to the FDA Advisory Committee in Support of Tofersen Approval

Mark HeidenAdvocacy, Foundation Blog, Home Page, Research News

RE: FDA-2022-N-0691

Dear FDA Advisory Committee:

We write to express our strong support for the approval of tofersen under the FDA’s Accelerated Approval Program. Our organization’s long history of scientific research into SOD1-ALS and our depth of experience supporting people with this form of the disease provide a unique perspective on the urgent and unmet need for this drug.

Founded in 1977, the Les Turner ALS Foundation is the oldest independent ALS group in the country. Our mission is to provide the most comprehensive care and support to people living with ALS and their families and to advance scientific research for the prevention, treatment and cure of ALS.

SOD1 was co-discovered by Teepu Siddique, MD, at the Les Turner ALS Center at Northwestern Medicine in 1993. It was the first genetic cause identified for ALS. This has been followed by additional discoveries at the Les Turner ALS Center on the molecular genetics of ALS and pioneering research into the role of upper motor neurons, stem cells and other critical factors in ALS, which continues today.

Our organization remains actively engaged in investigation of SOD1-ALS as well as care for patients with this form of the disease. The Lois Insolia ALS Clinic at the Les Turner ALS Center was a site for both the Phase 3 VALOR clinical trial of tofersen and the open label extension, and Senda Ajroud-Driss, MD, the clinic’s director and an associate professor of neurology at Northwestern University’s Feinberg School of Medicine, was a site investigator for the trial.

The FDA’s Accelerated Approval regulatory pathway is designed to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need. In the application, sponsors must identify a measure that is reasonably likely to predict clinical benefit to people receiving the treatment. In the case of tofersen, study results suggest that reductions in neurofilament levels predict slower progression of the disease.

As we have followed the clinical trials of tofersen, we have been encouraged by results that suggest an early start and extended use of tofersen may help stabilize muscle strength, respiratory function and quality of life.

The need for this treatment is urgent and unmet. The progression of SOD1-ALS can vary greatly from person to person. A 2017 study in the Journal of Neurology, Neurosurgery, and Psychiatry reported that SOD1-ALS has a median survival of 2.7 years, which falls to 1.2 years for patients with the faster-progressing A4V mutation. There is no FDA-approved treatment to target SOD1-ALS or any other genetic cause of ALS; tofersen would be the first.

Our support services coordinators have worked with multiple generations of families who have SOD1-ALS. When a person is diagnosed with a genetic form of ALS, it is a devastating blow, and the impact can be felt across generations. Not only do family members have to cope with the practical challenges of caring for someone with a debilitating disease, but they also live with the fear that they too, and possibly their children, will be diagnosed, and they must consider whether they will need to plan for their own care.

It is not uncommon to see several members of a family diagnosed with SOD1-ALS, each one facing their own unique challenges and struggles. We have worked with people who have lost a spouse and a child to the disease and continue to face each day with courage. We provided a wheelchair to one sibling and a few years later provided the same to their brother. Our support services coordinators are deeply involved with these families; one of our coordinators worked with children who were caregivers for their parent and then, 15 years later, the same coordinator provided support services to those adult children.

From firsthand experience, we can testify that the emotional trauma for these families is overwhelming. We counsel the person living with the disease as well as their family members through our support groups. Genetic counseling and genetic testing are informative options, and our organization strives to make these available to people living with ALS regardless of clinical presentation or family history.

But people living with SOD1-ALS need more than information. They need the chance to share more of their lives with their spouses, children and loved ones. They need cause to believe the pain of this terrible disease will be a different experience for the next generation. They need hope.

Nothing could mean as much to these families as the first therapy to slow the progression of SOD1-ALS – to a parent, knowing that if their child should be diagnosed, an early start and extended use of tofersen could give them a longer, richer and more fulfilling life. We look forward to the day when a person is given a copy of their SOD1 lab report, a prescription for tofersen and new hope for this genetic form of ALS.

We believe that tofersen represents a significant advancement in the treatment of SOD1-ALS. The need is urgent and unmet, and the evidence is compelling. We urge you to recommend accelerated approval of tofersen and bring hope to these families and their generations to come.


Andrea Pauls Backman
Chief Executive Officer
Les Turner ALS Foundation

Lauren Webb
Chief Advocacy and Outreach Officer
Les Turner ALS Foundation

As a non-profit advocacy organization, we receive less than 5% of our annual funding from Biogen as well as other pharmaceutical companies.