Spinraza (nusinersen) / Biogen, Ionis, Royalty - LARVOL DELTA

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

Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. (PubMed, Nat Med) - P3 | "STRENGTH ( NCT05386680 ) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating OAV101 IT in participants with SMA aged 2 to <18 years who discontinued nusinersen or risdiplam. The OAV101 IT safety profile was consistent with findings in treatment-naïve patients. Trial registration: ClinicalTrials.gov identifier: NCT05386680 ."

Clinical • Journal • P3 data • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases • Respiratory Diseases • Thrombocytopenia

Economic evaluations of disease-modifying therapies for spinal muscular atrophy: a systematic literature review. (PubMed, Orphanet J Rare Dis) - "The economic evaluation landscape for SMA treatments is evolving. However, challenges remain due to data gaps and methodological variability across studies. Future research should prioritise the integration of long-term real-world data into economic evaluations, consider the development of patient- and caregiver-derived utility values, and the use of transparent, standardised modelling approaches. These improvements will enhance the robustness, comparability, and policy relevance of economic evaluations in rare disease treatment funding."

HEOR • Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Effectiveness and Safety of Nusinersen and Risdiplam in Spinal Muscular Atrophy: A Systematic Review. (PubMed, Ann Clin Transl Neurol) - "This comprehensive review highlights the clinical effectiveness and safety of nusinersen and risdiplam across all SMA types. However, variability in outcomes and limited comparative data introduce uncertainty. The findings underscore the need for more high-quality randomised controlled trials to strengthen the evidence base for SMA treatment."

Journal • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

SMAII: Monitoring to the Evolution of Motor Function in SMA Type II Adults Patients Treated With SPINRAZA® (clinicaltrials.gov) - P=N/A | N=20 | Active, not recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Completed ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1 • SMN2

Real-Time Ultrasound-Guided Intrathecal Delivery of Nusinersen in Adult Patients With Spinal Muscular Atrophy and Complex Spinal Anatomy. (PubMed, Pain Physician) - "Real-time ultrasound-guided intrathecal administration of nusinersen is feasible and appears safe in adult patients with SMA and complex spinal anatomies. Further prospective, multi-center clinical trials are warranted to validate these findings and evaluate long-term safety and efficacy in a larger patient cohort."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Advances in SMA treatment: Lessons for ALS (ALS-MND 2025) - "Three disease modifying treatments (the IT-delivered splice switching anti-sense oligonucleotide nusinersen, the orally bioavailable splice modifying small molecule risdiplam, and the iv-administered AAV9-SMN gene therapy onasemnogene abeparvovec) increase SMN expression and can ameliorate disease features...As the experience with treated SMA patients grows, the new natural history of the disease is being defined including characterization of potential new phenotypes not previously recognized. Although SMA treatment development represents a remarkable success, it has raised multiple new questions that have relevance to ALS and other neurodegenerative disorders."

Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence. (PubMed, J Int Med Res) - "Over the past decade, disease-modifying therapies targeting the survival motor neuron pathway-nusinersen, onasemnogene abeparvovec, and risdiplam-have significantly transformed the clinical landscape of spinal muscular atrophy...As the field evolves, biomarker-based monitoring and combination therapies are emerging as promising complementary approaches. With growing clinical experience and an expanding body of pharmacokinetic research on targeted therapies, there is strong potential to further refine treatment strategies-ultimately making spinal muscular atrophy care more effective, safer, and more accessible for patients worldwide."

Journal • PK/PD data • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

CT-guided Lumbar Puncture for Intrathecal Nusinersen Injection in Patients with Spinal Muscular Atrophy: Technical Effectiveness, Safety, and Radiation Dose. (PubMed, Clin Neuroradiol) - "CT-guided lumbar puncture for intrathecal nusinersen injection is a safe and effective technique, even in complex spinal anatomy. Dorsal spondylodesis increases procedural complexity. Tailored puncture level selection, optimized positioning, and dose-reduction strategies are essential for high success rates and minimal radiation. While CT guidance ensures excellent anatomical visualization, fluoroscopy may reduce radiation and procedure time; future comparative studies should define optimal modality selection."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases

High Dose Regimen of Nusinersen Receives Positive CHMP Opinion for the Treatment of Spinal Muscular Atrophy (GlobeNewswire) - "The CHMP’s Positive Opinion will now be reviewed by the European Commission with a final decision expected in January 2026...The CHMP’s positive opinion is based on data from the three-part, Phase 2/3 DEVOTE study and its ongoing long-term extension which investigated the efficacy and safety of the high dose regimen of nusinersen in treatment-naïve and individuals previously-treated with the approved 12 mg dosing regimen."

CHMP • EMA approval • Muscular Atrophy

Hip Displacement in Spinal Muscular Atrophy in the Early Disease-Modifying Therapy Era: Association With Hip Pain and Timing of Therapy Initiation. (PubMed, J Pediatr Orthop) - "Hip displacement in SMA begins early, with progression patterns differing by disease severity. Hip displacement is also associated with pain, which was observed primarily in dislocated hips. These findings highlight the need for routine hip surveillance from early infancy and pain assessment. DMT initiation may confer only minimal benefit when instituted at a later age, but may yield more substantial benefit when administered presymptomatically soon after birth."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases

Risk, Time in Hospital, and Associated Costs? of Hospitalizations in Individuals With Infantile-Onset SMA: Results From DEVOTE Part B (ISPOR-EU 2025) - P3 | "Relative to the 12/12 mg group, trends in favor of treatment with 50/28 mg nusinersen were observed related to the lower risk of hospitalisation owing to SAE and reduced time in hospital that may lead to lower hospitalisation costs. These findings underscore the importance of understanding healthcare resource utilization in SMA treatment."

Clinical • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Potential Nephrocalcinosis Risk Linked to Nusinersin: Insights from FAERS-Based Signal Detection and Molecular Docking (ISPOR-EU 2025) - "This study identified nephrocalcinosis as a potential adverse signal associated with Nusinersen. The findings highlight the need for further pharmacogenetic and epidemiological investigations to validate this signal and explore underlying mechanisms and risk factors."

CNS Disorders • Genetic Disorders • Infectious Disease • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Nephrology • Rare Diseases • Ventriculomegaly • EGFR • GAPDH

A Systematic Literature Review on Costs and Healthcare Resource Utilization in Spinal Muscular Atrophy (ISPOR-EU 2025) - "Global SMA burden is substantial, with high costs of patient care and large impact on caregiver time. Early identification and treatment may reduce costs and HCRU."

HEOR • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Onasemnogene abeparvovec gene therapy for treatment of patients with spinal muscular atrophy: Updated real-world practical considerations. (PubMed, J Neuromuscul Dis) - "These include nusinersen and risdiplam, which modify splicing of the SMN2 pre-mRNA, and onasemnogene abeparvovec, a viral-mediated gene therapy...As more countries have approved onasemnogene abeparvovec and new data have emerged from clinical trials and real-world use, a similar expert panel provides updated recommendations along with additional guidance. Specific recommendations are centered around family preparation prior to and immediately following dosing to minimize risk of infectious illness, timing of anti-adeno-associated virus serotype 9 antibody titer testing for those patients with exclusionary titers, modifying immunization schedules, avoiding potential complications with long-term corticosteroid administration, safety monitoring, considerations for combination therapy, implementing newborn screening, and emphasizing the need for ongoing multidisciplinary care and adherence to standard-of-care guidelines."

Journal • Real-world evidence • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

Quebec Spinal Muscular Atrophy Newborn Screening Program: The First Year Experience. (PubMed, Int J Neonatal Screen) - "Surviving newborns initiated treatment at a median age of 30 days (range: 9-103 days), with four receiving onasemnogene abeparvovec and one nusinersen...Overall, the Quebec SMA NBS pilot program successfully identified affected newborns, facilitated early access to therapy, and provided the first provincial estimate of SMA birth prevalence. Improved sample shipping and processing times are needed to maximize the program's impact, which is expected with full automation."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Palliative care • Pediatrics • Rare Diseases • SMN2

Diverging Safety Signals: A Trend Analysis of Suspected Adverse Drug Reactions Reporting for Spinal Muscular Atrophy Therapies in the European Union. (PubMed, Neurol Int) - "Onasemnogene abeparvovec exhibited a continued but decelerating increase in suspected ADRs, while risdiplam demonstrated a consistent upward trend across all reported reactions. Diverging patterns in adverse reaction reporting suggest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec, underscoring the need for ongoing continued pharmacovigilance (e.g., post-authorization studies and spontaneous reporting)."

Adverse drug reaction • Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Updates of spinal muscular atrophy in advanced therapies. (PubMed, J Formos Med Assoc) - "There are remarkable advances in SMA treatment in the last decade with the approval of three disease-modifying therapies: nusinersen, an antisense oligonucleotide; onasemnogene abeparvovec, a gene replacement therapy; and risdiplam, an oral splicing modifier...As survival improves, new phenotypes and multisystem manifestations are emerging, underscoring the need for integrated multidisciplinary care and updated guidelines. Lessons learned from SMA therapy development may serve as a paradigm for other neurological diseases."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

Compound Muscle Action Potential (CMAP) Amplitude Trajectories and Pattern in Adults with 5q-Spinal Muscular Atrophy Receiving Nusinersen Therapy: A Multicenter, Binational Observational Study. (PubMed, Eur J Neurol) - "CMAP amplitudes remained stable during nusinersen treatment, with no differences in trajectories between SMA types 2 and 3. Our findings suggest that while CMAP amplitude correlates with disease severity, it may not serve as a sensitive biomarker of treatment response in adult SMA patients."

Clinical • Journal • Observational data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Today [Biogen] announced that high dose nusinersen (SPINRAZA) in SMA was successfully resubmitted with the FDA with an updated PDUFA date of April 3, 2026 (Biogen Press Release)

FDA filing • PDUFA • Muscular Atrophy

Assessment of Fine Motor Abilities Among Children with Spinal Muscular Atrophy Treated with Nusinersen Using a New Touchscreen Application: A Pilot Study. (PubMed, Children (Basel)) - " The findings suggest that the TATOO, alongside traditional assessment tools, offers a sensitive measure of fine motor function changes in patients with SMA. This study highlights the potential of touchscreen-based assessments to address gaps in current outcome measures and emphasizes the need for larger, multicenter studies that will include pre-treatment, baseline, and control data."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Real-world evidence on nusinersen treatment of persons with SMA: a focused review. (PubMed, J Neuromuscul Dis) - "The favorable clinical response and safety profile are discussed, as well as the emerging new phenotypes of disease. Nusinersen, one of three FDA-approved drugs for SMA (as of 2025) remains an important therapeutic consideration for infants, children and adults with SMA."

HEOR • Journal • Real-world evidence • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Drug Candidate BIO101 for Spinal Muscular Atrophy as Monotherapy or Combined With the Antisense Oligonucleotide ASO-10-27. (PubMed, J Cachexia Sarcopenia Muscle) - "We showed that BIO101 constitutes an efficient SMN-independent therapy to improve muscle performance in SMA, which could open new therapeutic avenues for patients in combination with SMN-based therapies, or as monotherapy for less severe forms."

Journal • Monotherapy • CNS Disorders • Fatigue • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Respiratory effects of nusinersen treatment in pediatric patients with spinal muscular atrophy types 2 and 3. (PubMed, Eur J Pediatr) - "Nusinersen may help preserve respiratory muscle strength and delay the need for ventilatory support among pediatric patients with SMA types 2 and 3. Although ppFVC declined, stability in other parameters supports a potential respiratory benefit."

Journal • Retrospective data • CNS Disorders • Cough • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Pulmonary Disease • Rare Diseases • Respiratory Diseases

A Study to Learn About the Effect of Nusinersen (BIIB058) Given as Injections to Children With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec (RESPOND) (clinicaltrials.gov) - P4 | N=46 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • CSF NfL • SMN1 • SMN2