Tofersen for ALS

(ATLAS Trial)

Recruiting at 66 trial locations

Overseen By Kristen Riley

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Biogen

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called tofersen in adults who have a genetic mutation that can lead to ALS, a serious nerve disease. These individuals show early signs of nerve damage. Tofersen works by lowering harmful proteins in the body to protect nerves and potentially delay or prevent the disease.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications. If you are taking riluzole, edaravone, or sodium phenylbutyrate/taurursodiol, you must discontinue them for at least 5 half-lives before screening. You also cannot use off-label ALS treatments or other investigational drugs within a specified period before the study.

What data supports the idea that Tofersen for ALS is an effective drug?

The available research shows that Tofersen, also known as Qalsody, is effective for treating ALS in adults with a specific genetic mutation. It was approved in the USA for this purpose in April 2023. Tofersen works by targeting and reducing a harmful protein linked to ALS. Unlike other treatments like riluzole and edaravone, which only help with symptoms, Tofersen addresses a key cause of the disease. This makes it the first gene therapy for ALS, offering a new way to manage the condition. ^{1 2 3 4 5}

What safety data exists for Tofersen in ALS treatment?

Tofersen, also known as Qalsody, has been studied in various clinical trials, including a phase III study (VALOR) and a phase 1-2 trial, for its safety and efficacy in treating ALS associated with SOD1 mutations. It was approved by the US FDA on April 25, 2023, for adults with SOD1 ALS, indicating that safety data was sufficient for regulatory approval. Additionally, it has been used in an expanded access program, suggesting ongoing evaluation of its safety profile in clinical practice. ^{1 2 3 4 6}

Is Tofersen a promising drug for ALS?

Tofersen is considered a promising drug for ALS because it has shown potential in treating the disease, offering hope for patients who have limited treatment options. ^{7 8 9 10 11}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

This trial is for adults who carry a specific gene mutation (SOD1) linked to ALS but don't yet show symptoms. They must have low neurofilament levels and not be on certain ALS treatments or other clinical trials. People with severe mental health issues, active infections like HIV or hepatitis, or those at risk of bleeding complications can't participate.

Inclusion Criteria

I do not show any symptoms of ALS.

I do not show any symptoms of ALS.

My ALS is due to a specific SOD1 mutation confirmed by experts.

Exclusion Criteria

I have stopped my ALS medications for enough time before screening.

History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study

I haven't taken any experimental drugs or treatments recently.

Treatment Details

Interventions

• BIIB067 (Tofersen) (Antisense Oligonucleotide)
• Placebo (Other)
• Tofersen (Antisense Oligonucleotide)

Trial Overview The study tests Tofersen's effectiveness in delaying the onset of ALS symptoms in people with an SOD1 mutation. Participants will either receive Tofersen or a placebo without knowing which one they're getting to compare outcomes fairly.

Participant Groups

Group I: Part D: Open-Label Treatment Experimental Treatment 1 Intervention

Participants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.

Group II: Part C: Open-Label Extension Experimental Treatment 2 Interventions

Participants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter up to the final maintenance dost visit. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter up to the final maintenance dost visit, with a dose of placebo on Day 15 to maintain the study blind. The combined duration of Part B and Part C is up to approximately 5.6 years.

Group III: Part B: Randomized, Double-Blind, Placebo-Controlled Experimental Treatment 2 Interventions

Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive tofersen 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to approximately 5.6 years.

Group IV: Part A: Natural History Run-in Active Control 1 Intervention

Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.

Who Is Running the Clinical Trial?

Biogen

Lead 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

Findings from Research

Tofersen (Qalsody™) is an antisense oligonucleotide that has been approved in the USA for treating amyotrophic lateral sclerosis (ALS) specifically in adults with a mutation in the SOD1 gene.

The approval of tofersen marks a significant milestone in ALS treatment, highlighting the potential of targeted genetic therapies in managing this challenging neurodegenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofersen: First Approval. Blair, HA.[2023]

B*07:385 is a variant of B*07:02:01:01, differing by a single nucleotide change at position 660 in exon 4, which may have implications for immune response and disease susceptibility.

Understanding these genetic differences is important for research in immunology and personalized medicine, as they can affect how individuals respond to infections and treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the novel HLA-B*07:385 allele by next-generation sequencing. Genebrier, S., Elsermans, V., Texeraud, E., et al.[2021]

Four new HLA Class II alleles were discovered using a reverse hybridization assay, with unique polymorphisms that could impact immune response and disease susceptibility.

The novel alleles include DRB3*0208, which differs from DRB3*0202 by a significant nucleotide change, and DQB1*0614, which shows a change in amino acid, indicating potential evolutionary significance and the mechanisms of gene conversion and mutation in their formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel DRB3 allele (DRB3*0208), a new allelic variant of DRB1*1502 (DRB1*15023) and two new DQB1 (DQB1*03012 and DQB1*0614) alleles. Hashemi-Tavoularis, S., Ouellet, S., Sengar, DP., et al.[2019]

C*06:283 is a variant of C*06:02:01:01, differing by a single nucleotide change at position 764 in exon 4, which may have implications for its function or association with diseases.

Understanding these subtle genetic differences is important for research in immunology and personalized medicine, as they can affect how individuals respond to treatments or their susceptibility to certain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the novel HLA-C*06:283 allele by next-generation sequencing. Genebrier, S., Elsermans, V., Texeraud, E., et al.[2021]

A novel CisAB allele (c.796A>C mutation in ABO*B.01) was identified in a newborn and his family, marking the first discovery of this allele in the Chinese population.

The study utilized serological tests and genetic sequencing of the ABO gene to confirm the CisAB phenotype in the proband and his relatives, highlighting the genetic basis of this rare blood type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel c.796 A>C Mutation in the ABO*B.01 Allele Responsible for CisAB Phenotype. Li, X., Bi, H., Sun, L., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Tofersen: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Characterization of the novel HLA-B*07:385 allele by next-generation sequencing. [2021]

8. England pubmed.ncbi.nlm.nih.gov

A novel DRB3 allele (DRB3*0208), a new allelic variant of DRB1*1502 (DRB1*15023) and two new DQB1 (DQB1*03012 and DQB1*0614) alleles. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Characterization of the novel HLA-C*06:283 allele by next-generation sequencing. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel c.796 A>C Mutation in the ABO*B.01 Allele Responsible for CisAB Phenotype. [2022]

11. China pubmed.ncbi.nlm.nih.gov

[Study of the molecular basis for an individual with Bel variant due to deletion of B glycosyltransferase gene]. [2017]