Qalsody (tofersen) / Biogen, Ionis - LARVOL DELTA

Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations. (PubMed, CNS Drugs) - "Tofersen had an acceptable tolerability profile in clinical trials with a favourable benefit-to-risk balance. In summary, tofersen is a new disease-modifying therapy for patients with ALS attributed to an SOD1 mutation, offering reductions in levels of a biomarker associated with neurodegeneration and disease progression, with an acceptable tolerability profile."

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

Long-term tofersen and cerebrospinal fluid macrophage inclusions in superoxide dismutase 1 amyotrophic lateral sclerosis. (PubMed, Can J Neurol Sci) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Tofersen treatment normalizes neurofilament levels in autosomal recessive SOD1 Amyotrophic Lateral Sclerosis. (PubMed, Can J Neurol Sci) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Development of an assay method for tofersen using IPRP-LC-HRMS with an extracting ion chromatogram processing approach. (PubMed, Anal Methods) - "Nusinersen (NSN) was utilized as the internal standard to mitigate variations in signal intensity of the mass spectrometer. The recovery from the formulation matrix, which was determined using the standard addition method with triplicate measurements at three concentration levels, was found to be within the range of 80-120%. Furthermore, the method exhibited precision and robustness for critical liquid chromatography parameters, such as flow rate and injection volume, and mass spectrometer parameters, including drying/desolvation temperature and gas flow."

Journal

A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis. (PubMed, Front Neurosci) - "ALS-associated genes are targeted by commonly used drugs, including Riluzole and Edaravone, and by the recently approved antisense oligonucleotide therapy (Tofersen). Moreover, we observed transcriptional dysregulation of ALS-associated genes in peripheral blood mononuclear cell and postmortem cortex samples. Overall, this ALS catalog can serve as a foundational tool for advancing early diagnosis, identifying biomarkers, and developing personalized therapeutic strategies."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Movement Disorders • Pulmonary Disease • Respiratory Diseases

Treatment of familial ALS with the drug tofersen (PubMed, Laeknabladid) - "The cerebrospinal fluid concentration of neurofilament light chain (Nf-L), a biomarker of neuronal axonal damage, has decreased to the reference range of healthy individuals. No serious side effects have been observed."

Biomarker • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL • NEFL • SOD1

Noninvasive quantification of fasciculations to track tofersen therapy in superoxide dismutase 1 amyotrophic lateral sclerosis. (PubMed, Clin Neurophysiol) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Serum Cardiac Troponin T Levels as a Therapy Response Marker in Tofersen-Treated ALS. (PubMed, Muscle Nerve) - "In this study, we describe a response signal of cTnT to tofersen treatment, which supports the value of cTnT as an independent biomarker in ALS. These results contribute to the notion that cTnT may provide additional value as a progression and treatment response biomarker in ALS complementary to NfL and warrant further investigation."

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

Spain Approves Groundbreaking Genetic ALS Treatment Tofersen for Public Use (Born2Invest) - "The Interministerial Commission on Drug Prices (CIPM) in Spain has approved the funding of Tofersén, an innovative treatment for amyotrophic lateral sclerosis (ALS), marketed under the name Qalsody. With this decision, according to the Ministry of Health, Spain is among the first European countries to incorporate this therapy into the public health system."

Reimbursement • Amyotrophic Lateral Sclerosis

The Unseen Progress: How PROs May Overlook the Value of Slowing Degenerative Decline (ISPOR 2025) - " The pivotal trials of recent Food and Drug Administration (FDA)-approved treatments for degenerative diseases were analyzed; these included nintedanib for idiopathic pulmonary fibrosis (IPF), tofersen for amyotrophic lateral sclerosis (ALS), ocrelizumab for primary-progressive multiple sclerosis (PPMS), and donanemab-azbt for Alzheimer’s disease (AD). PROs may not detect the benefit of treatment for degenerative diseases. A potential explanation is misalignment in patient expectations. Future research is needed to evaluate how treatment benefits can be appropriately captured by patient experience data."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases

Preclinical development of AAV mediated gene editing for SOD1-ALS using a Type V CRISPR-Cas enzyme (ASGCT 2025) - "QALSODY, a clinically validated antisense oligonucleotide dosed once a month via intrathecal injections, is approved for use in SOD1-ALS patients in the US and EU...Overall, these findings strongly support the continued development of Type V CRISPR-Cas enzymes for the potential treatment of CNS diseases. Disease Focus of Abstract:Inherited Neurological Disorders"

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

Base Editing Rescue of SOD1 associated ALS (ASGCT 2025) - "Antisense oligonucleotides (ASOs) targeting SOD1, known as tofersen, have been promising in reducing mutant SOD1 protein levels but require repeated administration, limiting their long-term feasibility... A gene-editing therapy that reduces the SOD1 transcript levels could serve as a one-time treatment for ALS patients with SOD1-linked disease. Our study demonstrated that Nme2 base editors are promising candidates, effectively reducing both mRNA and protein levels. By targeting a splice site, this approach is mutation-agnostic, making it broadly applicable to a larger ALS patient population."

Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Respiratory Diseases • SOD1

Analysis of the Burden of Illness, Treatment, and Health Disparities in Amyotrophic Lateral Sclerosis (ISPOR 2025) - "In Europe, riluzole and tofersen (ALS with SOD1 mutations) are the only approved pharmacological products, and in the United States (US), riluzole, edaravone, and tofersen have been approved by the Food and Drug Administration. ALS remains a disease with critical unmet needs. There is an immediate need for a new treatment that can help reduce the rate of progression of ALS, increase survival, and allow HRQOL to be maintained for longer durations. Addressing diagnostic delays and ensuring equitable access to emerging new and innovative therapies are essential steps toward reducing health disparities."

Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine. (PubMed, Expert Rev Neurother) - "Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce, with riluzole and edaravone offering only limited benefits...Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS...Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and potentially alter its natural course."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

Latest progress and challenges in drug development for degenerative motor neuron diseases. (PubMed, Neural Regen Res) - "The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy."

IO biomarker • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice. (PubMed, Mol Ther) - "Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene suppression a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen...Administered intraventricularly, di-siRNASOD1 extended survival in SOD1-G93A ALS mice, increasing survival beyond that previously seen in these mice by ASO modalities, slowed disease progression according to the standard ALS preclinical endpoints, and attenuated ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders."

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

Natural history of SOD1-ALS and potential treatment with tofersen (JSNE 2025) - "Co-sponsored by Biogen Japan Co., Ltd."

Clinical evaluation of the efficacy of intrathecal tofersen for familial ALS with SOD1 mutations (JSNE 2025) - No abstract available

Clinical • Amyotrophic Lateral Sclerosis • SOD1

Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies. (PubMed, Life (Basel)) - "Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies."

Heterogeneity • Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Movement Disorders • Proteinopathy • Respiratory Diseases • Sleep Disorder • FUS • NEFL • TARDBP

Disease Modification in SOD1-ALS With Tofersen May Result in Serious CNS Inflammation. (PubMed, Muscle Nerve) - No abstract available

Journal • CNS Disorders • Inflammation

SOD1-ALS mimicking an inflammatory neuropathy: a case report. (PubMed, Amyotroph Lateral Scler Frontotemporal Degener) - "We present the case of a 36-year-old patient with a rapidly progressing SOD1-ALS, who was initially diagnosed as inflammatory acute motor axonal neuropathy due to contrast-enhancement of the lumbar spinal cord and a pure secondary motor neuron phenotype. Since the initiation of tofersen, disease progression and neurofilament levels impressively declined."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Pain

Six recommendations, one recommendation and a protocol [Google translation] (Danish Medicines Council) - "The Danish Medicines Council recommends secukinumab for the skin disease moderate to severe hidradenitis suppurativa (HS) in adults with an inadequate response to conventional systemic treatment and treatment with at least one other biological drug. The recommendation only applies to dosing every 4 weeks....The Danish Medicines Council does not recommend tofersen as an addition to standard treatment for adult patients with amyotrophic lateral sclerosis (ALS) with a mutation in the superoxide dismutase 1 (SOD1) gene."

Reimbursement • Amyotrophic Lateral Sclerosis • Hidradenitis Suppurativa

Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen. (PubMed, Sci Rep) - "Given the limited data on tofersen's long-term efficacy in ALS due to its recent introduction, identifying biomarkers that predict clinical outcomes such as diminished therapeutic response or adverse effects is crucial. These biomarkers may help to better understand the underlying pathomechanisms of ALS and tofersen's role in modulating disease progression."

Biomarker • Clinical • Journal • CNS Disorders • Inflammation • CHI3L1 • SERPINA1

Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development. (PubMed, Ther Innov Regul Sci) - "Best practices for biomarker selection and strategies for health authority biomarker qualification programs are presented along with an overview of current limitations and challenges to optimizing biomarker applications along the drug development continuum from regulatory, translational, and operational perspectives."

Biomarker • Journal • Review • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Referral Patterns for Patients With Amyotrophic Lateral Sclerosis Enrolled in a US-Based Administrative Claims Database (AAN 2025) - "There are currently 3 US Food and Drug Administration-approved treatments for patients with ALS: riluzole, edaravone (Radicava® IV [intravenous] and Radicava ORS® oral suspension; Mitsubishi Tanabe Pharma America [MTPA]), and tofersen (for patients with a superoxide dismutase 1 mutation).Design/Patients with ALS continuously enrolled in Optum's de-identified Clinformatics® Data Mart (CDM) from January 2007 to December 2023 were included and grouped based on ALS treatment pattern (ie, untreated, riluzole-only, MTPA edaravone±riluzole)...These real-world data may help clinicians and payers better understand the referral patterns of patients with ALS, which may aid in reducing delays in diagnosis and treatment."

Claims database • Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Psychiatry