Tofersen for ALS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Riluzole, Edaravone

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Drug abuse, Active infection, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether tofersen is safe and effective for individuals with a type of ALS that does not involve SOD1. Researchers aim to determine if tofersen reduces a protein linked to nerve damage and improves quality of life. Participants will receive doses of tofersen through a lumbar puncture over 24 weeks. Suitable candidates have experienced ALS-related weakness for 2 years or less and tested negative for certain genetic mutations. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you are taking riluzole or edaravone, you can continue them as long as you have been on a stable dose for a certain period before starting the trial. The protocol does not specify about other medications, so it's best to discuss with the study team.

Is there any evidence suggesting that tofersen is likely to be safe for humans?

Research has shown that tofersen is generally safe for treating ALS. In earlier studies, 50 people took tofersen, and it was well-tolerated. It also helped lower levels of the SOD1 protein, which is linked to ALS. The FDA has already approved tofersen for treating a specific type of ALS caused by SOD1 mutations, indicating its likely safety. However, like any treatment, some side effects may occur. Discussing possible risks with the trial team before joining is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Unlike most treatments for ALS, which primarily aim to manage symptoms, Tofersen targets the root cause of the disease by reducing the production of a toxic protein called SOD1. This protein is linked to a genetic mutation found in some ALS patients. Researchers are excited about Tofersen because it offers a more targeted approach, potentially slowing or halting disease progression rather than just alleviating symptoms. This could mean a significant breakthrough in treating ALS, providing hope for patients with this specific genetic form of the disease.

What evidence suggests that tofersen might be an effective treatment for non-SOD1 ALS?

Research has shown that tofersen, the investigational treatment in this trial, can help treat SOD1 ALS by lowering levels of neurofilament light chain (NfL), a marker of nerve damage. In earlier studies, tofersen reduced NfL levels by up to 50% within 12-16 weeks, suggesting it may slow nerve damage. For patients with SOD1 ALS, tofersen has also been linked to slower declines in movement, breathing, and muscle strength. Although tofersen is approved for SOD1 ALS, its effects on other types of ALS remain under investigation. The way it works in SOD1 ALS, such as reducing NfL, might also benefit other types of ALS, but further research is needed. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with non-SOD1 ALS, also known as Lou Gehrig's Disease. Participants must be able to undergo lumbar punctures and complete various tests and questionnaires over a period of 32 weeks.

Inclusion Criteria

SVC ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position)

I started edaravone at least 60 days ago and plan to continue it through the study.

My genetic tests for SOD1 and FUS mutations were negative.

Exclusion Criteria

Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment

I have a condition or risk that could cause serious bleeding during or after surgery.

Current enrollment in any other interventional study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 100mg tofersen via lumbar puncture at specified intervals over 24 weeks

24 weeks

8 visits (in-person) at Weeks 0, 2, 4, 8, 12, 16, 20, and 24

Follow-up

Participants complete follow-up visits to monitor safety and effectiveness after treatment

8 weeks

2 visits (in-person) at Weeks 28 and 32

What Are the Treatments Tested in This Trial?

Interventions

• Tofersen

Trial Overview

The trial is testing Tofersen, administered via lumbar puncture at specific intervals over 24 weeks, to see if it lowers neurofilament light chain levels in blood/CSF, improves clinical outcomes or quality-of-life measures in non-SOD1 ALS patients.

How Is the Trial Designed?

Group I: Tofersen Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Biogen

Industry Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12003547/

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic ...

Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2204705

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

Results. A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have ...

3.

als.org

als.org/navigating-als/living-with-als/fda-approved-drugs/tofersen

Tofersen

By 12-16 weeks, tofersen reduced bloodstream levels of NfL, a biomarker of neuron damage and neurodegeneration, by 50%. These biomarker changes were ...

4.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00074-9/fulltext

Effects of tofersen treatment in patients with SOD1-ALS in a ...

Based on pre-existing evidence, treatment with tofersen in SOD1-ALS leads to a reduction in neurofilament levels (NfL). This study provides ...

5.

ir.ionis.com

ir.ionis.com/news-releases/news-release-details/ionis-partner-biogen-announces-results-phase-3-valor-study-and

Ionis partner Biogen announces that results from Phase 3 ...

The data show that earlier initiation of tofersen, compared to delayed initiation, slowed declines in clinical function, respiratory function, muscle strength ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12060635/

Serious Neurologic Adverse Events in Tofersen Clinical Trials ...

Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (SOD1‐ALS).

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07223723

NCT07223723 | A Study to Learn More About the Long- ...

The primary objective of this study is to evaluate the safety of tofersen in participants with SOD1-ALS in post marketing setting in China. The ...

8.

frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1687698/full

Comparative safety analysis of Riluzole, Edaravone and ...

In 2023, Tofersen was approved in the United States for the treatment of adult amyotrophic lateral sclerosis with mutations in the superoxide dismutase 1 (SOD1) ...