Qalsody (tofersen) / Biogen, Ionis - LARVOL DELTA

Chronic Non-Progressive Neurophysiology in an ALS Patient Treated With Tofersen for 6 Years. (PubMed, Muscle Nerve) - No abstract available

Journal

Genetic ALS-Progressive Sleep Defects Precede the Onset of Clinical Disease. (PubMed, Eur J Neurol) - "Sleep macro- and microarchitectural abnormalities progressively worsen during the premanifest phase of ALS. These findings suggest that polysomnography-derived sleep measures and their neurochemical correlates may serve as sensitive, noninvasive surrogate biomarkers of disease progression in clinically silent ALS. This could support disease prevention, for example, by the antisense oligonucleotide tofersen in patients carrying SOD1 mutations."

Journal • Observational data • Amyotrophic Lateral Sclerosis • CNS Disorders • Sleep Disorder • SOD1

From Vision to Validation: The Journey of Tofersen in Superoxide Dismutase 1 Gene-Associated Amyotrophic Lateral Sclerosis. (PubMed, Mayo Clin Proc Innov Qual Outcomes) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Presymptomatic Amyotrophic Lateral Sclerosis: From Early Biomarker Detection to Phenoconversion Prediction. (PubMed, Diagnostics (Basel)) - "The ATLAS study, a trial of tofersen initiated in clinically presymptomatic carriers of superoxide dismutase 1 (SOD1) variants, incorporated specific SOD1 variants and within-person NfL increases into risk monitoring and used these criteria to select participants for the randomized treatment phase. Evidence remains concentrated in a few genetic subtypes, and no single marker accurately predicts individual phenoconversion. Identification requires genotype-specific natural history, serial clinical examinations and biomarker testing, with clinical utility validated in independent longitudinal cohorts and prevention trials."

Biomarker • Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • SOD1 • TARDBP

Emergencies in Amyotrophic Lateral Sclerosis. (PubMed, Muscle Nerve) - "Although serious adverse events from ALS treatments are very rare, potential immune-mediated neurologic complications are a consideration with tofersen use...Anticipation of potential complications and emergencies, combined with an understanding of appropriate evaluation and evidence-based management, constitute critical components of caring for pALS. Early recognition and proactive management of these emergencies can improve safety, reduce avoidable hospitalizations, and support goal-concordant, patient-centered care."

Journal • Review • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Cognitive Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Respiratory Diseases

Long-term (5 years) evaluation of tofersen in SOD1‑ALS: final results from the integrated analysis of Study 101 Parts A/B, a Phase 1/2 ascending dose trial, and the open-label extension (NEALS 2026) - No abstract available

Clinical • P1/2 data

Update on ATLAS, a presymptomatic interventional study of tofersen in SOD1-ALS (NEALS 2026) - No abstract available

Clinical

Serum Neurofilament Light Chain and GFAP in Amyotrophic Lateral Sclerosis on a Commercial ECLIA Platform. (PubMed, Muscle Nerve) - "Serum NfL on a commercial ECLIA platform retained its strong correlation with progression rate despite unstructured sampling, replicating SIMOA-based findings at platform-specific values. NfL tracked the rate of decline rather than the accumulated disease state; GFAP and S-100B added no prognostic or disease-specific information."

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

Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design. (PubMed, Drug Des Devel Ther) - "These include the modest survival benefit of riluzole, the narrow eligible population for edaravone, and the complex trajectory of sodium phenylbutyrate-taurursodiol, which received accelerated approval but was subsequently voluntarily withdrawn after its confirmatory Phase III trial failed to meet its primary endpoints. Future success depends on establishing multimodal biomarker panels, implementing genetic testing-guided individualized therapy, developing combination regimens, and integrating patient-reported outcomes with palliative care. Although substantial challenges remain, the clinical success of Tofersen provides evidence that precision therapeutic strategies may gradually transform ALS management toward a more individualized and disease-modifying approach."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Inflammation • Palliative care

SOD1 Variants in Patients With Amyotrophic Lateral Sclerosis in Central Eastern Europe: From Genetic Testing to SOD1 Targeted Therapy. (PubMed, Eur J Neurol) - "This study provides the first comprehensive overview of SOD1-ALS in Central Eastern Europe. Our findings underscore the importance of genetic testing and counseling, as well as equitable access to targeted therapies such as Tofersen to advance patient-specific care in this region."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view. (PubMed, Front Neurol) - "Establishing the underlying genetic basis in both sporadic and familial ALS is essential, as it enables individualized and family genetic counseling, facilitates the early identification of at-risk or oligosymptomatic relatives, improves the prediction of gene-specific clinical trajectories, and, more recently, determines eligibility for gene-targeted therapies, such as tofersen for SOD1-associated ALS and ulefnersen, currently under clinical investigation, for FUS-associated ALS. However, accumulating clinical evidence has increasingly supported the timely and early implementation of genetic testing as part of the standard clinical management of patients with ALS. In this article, we present the perspective of leading Brazilian neurologists specializing in ALS care regarding the current role of genetic testing in clinical practice."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • FUS

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 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2027 ➔ May 2027 | Trial primary completion date: Dec 2027 ➔ May 2027

Enrollment closed • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Severe hypersensitivity reaction during tofersen therapy in amyotrophic lateral sclerosis associated with the rare SOD1 p.Val120Phe mutation. (PubMed, Neurol Neurochir Pol) - No abstract available

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

Blood SOD1 Activity in ALS Patients Receiving Tofersen Treatment. (PubMed, Ann Neurol) - "The data indicate that the positive tofersen treatment effect is independent of SOD1 activity. Lower SOD1 activity is specific to SOD1-ALS, already present in the asymptomatic phase and depends on the mutation type. Future studies should determine whether tofersen treatment affects cerebrospinal fluid (CSF) SOD1 activity. ANN NEUROL 2026."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study). (PubMed, Mayo Clin Proc Innov Qual Outcomes) - "Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen."

Clinical • HEOR • Journal • Real-world evidence • Retrospective data • NEFL • Plasma NfL • SOD1

Tofersen treatment in respiratory onset amyotrophic lateral sclerosis and a variant of uncertain significance in SOD1; a case report. (PubMed, Eur J Hum Genet) - "Functional decline on the ALSFRS-R slowed from 1.52 points per month pre-treatment to 0.52 points per month post-treatment, muscle strength remained stable, and EQ-VAS quality of life scores remained between 60 and 70. The ability to evaluate treatment response on an individual level will help to determine the clinical relevance of VUS as new gene-targeted treatments for ALS become available."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL

SOD1-lowering therapy for patients with wildtype SOD1-ALS: a case report. (PubMed, Amyotroph Lateral Scler Frontotemporal Degener) - "The time from symptom onset to death was 9 months. While treatment was initiated relatively late (∼7 months) after symptom onset and follow-up duration was short, the observed increase (as opposed to a reduction) in serum NfL and accompanying rapid functional decline, suggest the lack of a therapeutic effect in someone with fast progressing non-SOD1 ALS."

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

Half-Life as a Therapeutic Design Axis: Targeting Short-Lived lncRNAs With Antisense Oligonucleotides. (PubMed, IUBMB Life) - "Two back-to-back 2012 surveys-BRIC-seq in human HeLa and actinomycin-D microarray in mouse Neuro-2a-yielded similar median lncRNA half-lives of 3.4 and 3.5 h, with a short-lived fraction we term short-lived noncoding transcripts (SLiTs; t1/2 < 4 h). We (i) develop a kinetic framework for how target half-life shapes ASO pharmacodynamic onset, (ii) survey the cross-species half-life landscape, (iii) propose a decay-pathway-aware ASO design framework aligning modality choice with endogenous decay machinery, (iv) re-read representative clinical ASO cases (nusinersen, tofersen, tominersen, MALAT1 ASOs) through the half-life lens, and (v) outline a half-life-aware preclinical roadmap. Treating half-life symmetrically-engineered up in vaccine RNAs, exploited downward in endogenous targets-highlights a largely unoccupied design space for next-generation oligonucleotide therapeutics."

Journal • Review • CDKN2B • GAS5 • HOTAIR • MALAT1 • NEAT1

An intrathecal therapeutics clinic for administration of tofersen in amyotrophic lateral sclerosis: A Canadian nurse practitioner and neurologist collaborative model. (PubMed, Can J Neurol Sci) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

A changed landscape: five-year retrospective on the paradigm shift in genetic testing practices for ALS in Canada. (PubMed, Eur J Hum Genet) - "Offering genetic testing is increasingly recommended for all individuals with amyotrophic lateral sclerosis (ALS), particularly following the development of gene-targeted therapies, such as tofersen for SOD1-ALS...Proactive planning during the clinical trial phase facilitated rapid, nationwide adoption. This study captures a key turning point in ALS care, illustrating how therapeutic breakthroughs can redefine national clinical standards."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Antisense Oligonucleotide Tofersen Distribution in the Central Nervous System of SOD1-ALS Autopsy Tissue Donors. (PubMed, JAMA Neurol) - P3 | "Meningeal and perivascular lymphocytic immune responses were observed in 5 recently treated tissue donors but were not apparent in tissue donors with remote final tofersen doses. This case series presents the first emerging autopsy tissue data confirming the predicted distribution of tofersen and robust SOD1 protein reduction in human somatic motor systems tissues."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Tofersen in the treatment of SOD1 ALS – a two year experience from the Polish Early Access Program (EAN 2026) - "The data from a long term follow-up supports the efficiency of tofersen in SOD1-ALS."

CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Respiratory Diseases • Ulcerative Colitis • SOD1

Early and severe masticatory muscle involvement in SOD1-ALS: a case report with biomarker-clinical dissociation. (PubMed, Neurol Sci) - No abstract available

Biomarker • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Macrophage inclusions in patients undergoing antisense oligonucleotide therapy for ALS or SMA: A retrospective and transversal study. (PubMed, Rev Neurol (Paris)) - "Macrophagic inclusions appear more frequent in the CSF of tofersen-treated patients than previously reported. While their origin remains unclear, they seem linked to CSF inflammation without precluding a beneficial therapeutic response."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Inflammation • Movement Disorders • Rare Diseases • NEFL • SMA4 • SMN1 • SOD1

Short-Term Outcome of Tofersen Treatment in Patients with SOD1-ALS at a Tertiary Academic Center (ICNMD 2026) - "Tofersen was associated with stabilization of motor function across multiple clinical scales, with improvement observed in some patients. Importantly, all patients carried the SOD1 D77V mutation, a subtype linked to rapid functional decline, typically losing ~0.8–1.0 ALSFRS-R points per month (~10–12 points/year) in natural history. In contrast, our cohort showed a mean gain of +0.7 points over 3–6 months, and no patient experienced decline—an outcome highly unexpected for this aggressive genotype."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1