Qalsody (tofersen) / Biogen, Ionis - LARVOL DELTA

PRECLINICAL BLOOD-BRAIN BARRIER DELIVERY PLATFORM BASED ON LOW-INTENSITY PULSED ULTRASOUND (LIPU) SONOCLOUD® FOR NEURODEGENERATIVE DISEASE TARGETED THERAPEUTICS (ADPD 2026) - "The current LIPU+MB protocol improved the BBB crossing of Tofersen, suggesting that SonoCloud® is a promising platform to improve brain uptake of oligonucleotides and potentially other therapeutic modalities. This platform, combined with behavioral, electrophysiological, and translational biomarker readouts, can be used to generate comprehensive preclinical efficacy and safety data."

Preclinical • CNS Disorders • Plasma NfL • SOD1

Identification of tofersen PD-response biomarkers in VALOR clinical trial CSF via multiplexed quantitative proteomics. (PubMed, Cell Rep Med) - "We orthogonally confirm this observation by GPNMB immunoassay in independent tofersen-treated cohorts. Taken together, these data identify pharmacodynamic-response biomarkers of tofersen treatment that can be measured as early as 4 weeks post-treatment in SOD1-ALS patients and demonstrate the utility of leveraging unbiased proteomic screening integrated with targeted validation methods to identify pharmacodynamic-response biomarkers in clinical trial patient samples."

Biomarker • Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Melanoma • Oncology • Solid Tumor • GPNMB • SOD1

Tofersen treatment in SOD1 p.Leu145Phe ALS: real-world outcomes in a genetically homogeneous Croatian cohort. (PubMed, Amyotroph Lateral Scler Frontotemporal Degener) - "These findings provide real-world clinical context but do not permit conclusions regarding treatment efficacy. Further mutation-specific studies incorporating prospective baseline assessment and biomarker monitoring are needed to clarify therapeutic impact."

Journal • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders

QUANTIFYING THE OPPORTUNITY: THE ECONOMIC AND COMMERCIAL CASE FOR ALS TREATMENT INNOVATION (ISPOR 2026) - "Second, we estimated commercial value using proxy pricing based on tofersen, scaled to the full ALS population over a 10-year horizon... ALS represents a major opportunity for health impact and economic value. Yet, current HTA frameworks systematically undervalue innovation in rare, severe, progressive diseases with high unmet need and high background care costs. Policy reforms incorporating broader value elements are essential to incentivise investment and accelerate therapeutic development in ALS."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders

New Model for Treatment of ALS Pseudo-progression in SOD1-associated ALS With Tofersen (AAN 2026) - "She received a single dose of intrathecal hydrocortisone 50 mg and intravenous methylprednisolone 1 g daily for 5 days, resulting in significant improvement in her sensorimotor symptoms.Tofersen along with 50 mg intrathecal methylprednisolone was resumed 5 weeks after her last dose. Tofersen-induced myelitis is a form of ALS pseudo-progression which can lead to early termination of the life-saving medication. In this patient, early recognition and treatment with intrathecal steroids and rituximab led to a favorable long-term outcome. This highlights the importance of recognition of this adverse effect as well as a novel treatment paradigm to avoid discontinuing Tofersen."

Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • NEFL • SOD1

A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Participants With Superoxide Dismutase 1 (SOD-1) Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P=N/A | N=125 | Not yet recruiting | Sponsor: Biogen | N=69 ➔ 125

Enrollment change • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review. (PubMed, Int J Mol Sci) - "While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Metabolic Disorders • Proteinopathy • Transplantation • FUS • TARDBP

Safety profile of tofersen in amyotrophic lateral sclerosis: a systematic review and meta-analysis. (PubMed, Neurol Sci) - No abstract available

Journal • Retrospective data • Review • Amyotrophic Lateral Sclerosis • CNS Disorders

Evolution of requests for presymptomatic genetic testing for Amyotrophic Lateral Sclerosis – Frontotemporal Dementia: experience of the neurogenetics department of Pitié-Salpêtrière. (HMGC 2026) - "The second most frequently implicated gene was GRN (9%) until 2020, surpassed since 2021 by SOD1 (12% vs. 6% during the period 2008–2020), possibly related to the availability of Tofersen-targeted therapy...In particular, the unique nature of genes associated with ALS/FTD, such as C9orf72, which combine a risk of rapid progression with two major but distinct pathologies, amplifies uncertainty and presents psychologists with new challenges in providing support, both for at-risk individuals and their families. Prospective studies, including a psychosocial component, are needed to develop appropriate recommendations."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Huntington's Disease • Movement Disorders • GRN

Treating SOD1-ALS with tofersen results in nonprogressive chronic ALS-a case series from Iceland. (PubMed, J Neurol) - "Notably, we observed a clinically meaningful effect in two patients who had been ill for several years before treatment was instituted, raising questions about who should receive treatment and the biology of paresis and motor neuron cell loss in patients with ALS. Although only a minority of ALS patients carry a SOD1 mutation, the advent of this new precision medicine has profound implications for ALS management."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • SOD1

Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis. (PubMed, JAMA Neurol) - P3 | "Final data from VALOR and the OLE demonstrated the benefit of tofersen in SOD1-ALS and provide clear rationale for its use in this population. ClinicalTrials.gov Identifier: VALOR NCT02623699; OLE NCT03070119."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Gene-targeted versus broad-spectrum therapies in ALS: comparative lessons and strategic outlook. (PubMed, J Genet Genomics) - "While gene therapies like tofersen demonstrate clear molecular target engagement, their translation to robust clinical benefit remains a challenge...The future of ALS therapeutics therefore depends on a strategic pivot toward personalized medicine. This requires prospectively stratifying patients, developing rational combination therapies, and intervening earlier in the disease course, ultimately treating ALS as a syndrome of distinct molecular diseases rather than a single entity."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Rare Diseases • Respiratory Diseases

Introduction to the Supplement. (PubMed, Muscle Nerve) - "Three active pharmaceutical agents are currently approved by the United States Food and Drug Administration (FDA) for ALS: riluzole, edaravone (including intravenous [IV] and oral suspension formulations), and tofersen. Study MCI186-19 (Study 19) was a pivotal, phase 3 randomized controlled trial that demonstrated a significant reduction in physical functional decline vs. placebo in Japanese patients with ALS and contributed to FDA approval of IV edaravone in 2017...Topics include safety in clinical practice, generalizability of efficacy, clinical treatment outcomes, and health economics and outcomes research studies. Together, these findings aim to inform clinicians, researchers, and stakeholders regarding the evolving evidence base for edaravone in the management of ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis. (PubMed, Ann Pharmacother) - "Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL • SOD1

Addendum to the 2023 clinical practice guidelines for amyotrophic lateral sclerosis in Japan: approval and integration of novel disease-modifying therapies. (PubMed, Rinsho Shinkeigaku) - "Following the development of the 2023 guidelines, three additional medications-oral edaravone, high-dose intramuscular mecobalamin, and tofersen-have been introduced...The objectives of this addendum are twofold: to present these advances and recommendations in English to foster international collaboration, and to inform the global ALS community about the latest therapeutic strategies in Japan. In addition, ongoing efforts to harmonize clinical evaluation standards and promote international clinical trials are highlighted, with the goal of improving patient outcomes and advancing ALS research worldwide."

Clinical guideline • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P4 | N=12 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

Pharmacotherapy of neuromuscular diseases : what's new in 2025 (PubMed, Rev Med Suisse) - "Two new drugs have recently become available for treating neuromuscular diseases: omaveloxolone and tofersen. Tofersen is an antisense oligonucleotide that induces posttranscriptional silencing of the SOD1 (superoxide dismutase 1) gene, which is involved in familial forms of amyotrophic lateral sclerosis. Although its efficacy has so far only been indirectly demonstrated through its ability to reduce serum neurofilament levels, it is available on a compassionate use basis in Switzerland."

Journal • Amyotrophic Lateral Sclerosis • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders • SOD1

Facial-onset SOD1 amyotrophic lateral sclerosis: A case report and systematic review. (PubMed, J Clin Neurosci) - "Facial-onset SOD1 ALS defines a distinctive phenotype characterised by LMN-predominant facial palsy in early phases, near-neighbour spread, and an aggressive course exceeding genotype-based expectations. Prompt recognition and genetic testing in progressive facial palsy unresponsive to immunotherapy are essential to ensure access to gene-targeted treatments."

IO biomarker • Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders

New Drug Therapies Against Targeting Neurodegenerative Diseases: A Comprehensive Review. (PubMed, Cent Nerv Syst Agents Med Chem) - "In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease...In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition...In vascular dementia, numerous in vivo trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated in vivo and in vitro models of the primary neurodegenerative diseases."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Tofersen, SOD1, and the Treatability of Amyotrophic Lateral Sclerosis. (PubMed, JAMA Neurol) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

The Journal of the American Medical Association (JAMA) Neurology Publishes Long Term Results from the QALSODY Phase 3 VALOR Study and its Open-Label Extension in SOD1-ALS (Biogen Press Release) - "These results show that early initiation of QALSODY was associated with numerically slower decline in measures of clinical function, breathing and strength, as well as reduction in the risk of death or permanent ventilation. Sustained reductions in neurofilament, a marker of neurodegeneration, further validate the clinical results and demonstrate QALSODY’s impact on the underlying biology of SOD1-ALS."

P3 data • Amyotrophic Lateral Sclerosis

Tofersen in Non-SOD1 ALS (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Washington University School of Medicine

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL • Plasma NfL

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Anti-PF4 antibodies are a potential mediator of antisense oligonucleotide (ASO)-induced thrombocytopenia. (ASH 2025) - "Twelve ASOs, Inotersen, Eplontersen,Olezarsen, Fomivirsen, Mipomersen, Tofersen, Nusinersen, Eteplirsen, Golodirsen, Viltolarsen,Casimersen (all FDA approved) and Volanesorsen (EMA approved) were evaluated in this study. With two ASOs, Fomivirsen and Eteplirsen, direct activation of platelets was noted. Studieswith additional ASOs revealed a novel immune mechanism involving ASO-PF4 complex formation andanti-PF4 antibody recognition that can plausibly mediate ASO-induced thrombocytopenia. These findingshighlight the key role PS linkages may play in ASO immunogenicity and provide a mechanistic frameworkfor risk mitigation in ASO drug design, supporting the safer development and broader application of ASOtherapeutics."

Hematological Disorders • Thrombocytopenia

Canadian HTA Assessments Recognize Therapeutic Value of QALSODY (tofersen injection) and its Potential to Modify Disease Progression in Individuals Living with SOD1-ALS (Canada Newswire) - "CDA issues positive reimbursement recommendation for QALSODY; INESSS recognizes QALSODY's promising clinical value and highlights path toward reimbursement."

Reimbursement • Amyotrophic Lateral Sclerosis