Qalsody (tofersen) / Biogen, Ionis - LARVOL DELTA

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

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

The Unseen Progress: How PROs May Overlook the Value of Slowing Degenerative Decline (ISPOR 2025) - "This study examines the relationship between clinical outcomes and PROs in degenerative diseases, focusing on patient perceptions of treatments that slow progression. 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

Examination of the effect of intrathecal tofersen injection on familial ALS with SOD1 mutation in actual clinical practice (JSNE 2025) - No abstract available

Clinical • Amyotrophic Lateral Sclerosis • SOD1

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

Treatment of Amyotrophic Lateral Sclerosis in General and Specialist US Healthcare Settings: Results From a Real-World Survey (AAN 2025) - "Of those receiving treatment, 66% were prescribed riluzole formulations (52%, 78%), 36% IV or oral edaravone (45%, 28%), and 5% tofersen (7%, 3%)...These initial findings highlight the complex treatment landscape for pALS in the US, with substantial use of specialist care and diverse pharmacological approaches reflecting the varied needs of patients in managing their disease."

Clinical • Real-world • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders • Pain

ATLAS: A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation (clinicaltrials.gov) - P3 | N=158 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

QALSODY (tofersen injection) Receives Conditional Marketing Authorization from Health Canada as the First ALS Treatment Targeting a Genetic Cause (Canada Newswire) - "Biogen Canada Inc. announced today that Health Canada has issued marketing authorization with conditions (Notice of Compliance with Conditions (NOC/c)) for QALSODY (tofersen injection) for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene...Authorization in Canada under the NOC/c guidance was granted based on the acceptable safety profile, high quality and promising efficacy of QALSODY observed in the 28-week randomized, double-blind, placebo-controlled Phase 3 VALOR trial, which enrolled 108 patients aged 23 to 78 years with weakness attributable to ALS and a confirmed SOD1 mutation, and its open-label extension (OLE)."

Canada approval • Amyotrophic Lateral Sclerosis

Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis. (PubMed, Muscle Nerve) - "Some antisense oligonucleotides (ASOs) have been described as having pro-inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit/risk of tofersen treatment for SOD1-ALS. Safety data from the open-label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in SOD1-ALS."

Adverse events • Journal • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Hypertension • Infectious Disease • SOD1

Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects. (PubMed, J Neurol) - "Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies...Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders

Tofersen for Amyotrophic Lateral Sclerosis: Genetic Treatment With Precision Medicine: The Future of ALS Treatment. (PubMed, J Clin Neuromuscul Dis) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies

Ionis reports fourth quarter and full year 2024 financial results (Businesswire) - "'Over the next three years, we expect three more independent launches, including donidalorsen later this year for hereditary angioedema and olezarsen for severe hypertriglyceridemia in 2026, pending Phase 3 results in the second half of this year. Additionally, our partners are on track to launch four Ionis-discovered medicines over the same time period, including several that address broad patient populations'...WAINUA...Generated sales of $85 million resulting in royalty revenue of $20 million in the year ended December 31, 2024...SPINRAZA...generated global sales of $1.6 billion resulting in royalty revenue of $216 million in year ended December 31, 2024...Higher dose nusinersen under regulatory review in U.S. (PDUFA date of September 22, 2025) and EU. QALSODY (tofersen) for the treatment of SOD1-ALS generated global sales of $32 million resulting in royalty revenue of $4 million in the year ended December 31, 2024."

Launch • P3 data • PDUFA • Sales • Amyloidosis • Amyotrophic Lateral Sclerosis • Cardiovascular • Genetic Disorders • Hereditary Angioedema • Muscular Atrophy • Severe Hypertriglyceridemia

Tofersen for Amyotrophic Lateral Sclerosis: A Step Forward or Another False Hope? (PubMed, J Coll Physicians Surg Pak) - "Null."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights. (PubMed, J Neurol) - "This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments."

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

Tofersen and other antisense oligonucleotides in ALS. (PubMed, Ther Adv Neurol Disord) - "Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?"

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Immunology • Movement Disorders • Rare Diseases • SOD1

ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy. (PubMed, Curr Pharm Des) - "Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese Medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Gene Therapies • Inflammation

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis. (PubMed, Neurol Sci) - "Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option."

Journal • Retrospective data • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL • NEFL • SOD1

Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a "real-world" setting. (PubMed, Ann Clin Transl Neurol) - "This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers."

Journal • Real-world evidence • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders. (PubMed, Semin Respir Crit Care Med) - "For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years...For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein...For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease..."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Movement Disorders • Myasthenia Gravis • Pompe Disease • Rare Diseases • SMN2

Groundbreaking Directive Ensures ALS Patients on Medicare Advantage Gain Access to Qalsody (PRNewswire) - "The Centers for Medicare & Medicaid Services (CMS) has announced a first-of-its-kind directive requiring Medicare Advantage plans to approve coverage for Qalsody, a treatment for people living with genetic SOD1-ALS. This decision reflects the ALS Association's commitment to ensuring that people living with ALS have access to promising ALS treatments without delay."

Reimbursement • Amyotrophic Lateral Sclerosis • CNS Disorders

Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to murine brain. (PubMed, J Control Release) - "In the current study, we demonstrate effective systemic delivery of a next-generation SOD1 ASO (Tofersen) into the brain of wildtype and G93A-SOD1 transgenic C57BL/6 mice using calcium phosphate lipid nanoparticles (CaP lipid NPs)...Importantly, the BBB opening was transient without evidence of structural changes, neuroinflammation or damage to the brain tissue, indicating that the treatment is well tolerated. Overall, our results highlight FUS-assisted nanoparticle delivery of ASOs as a promising non-invasive therapeutic strategy for the treatment of ALS and CNS diseases more broadly."

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