Evrysdi (risdiplam) / SMA Foundation, PTC Therapeutics, Roche, Royalty - LARVOL DELTA

Fibro-adipogenic progenitor cells from murine SMA muscles are intrinsically adipogenic. (PubMed, Proc Natl Acad Sci U S A) - "Primary FAPs isolated from C/C SMA muscles mirrored heightened adipocyte formation, which was normalized by increasing Smn activity with Risdiplam. Conversely, adipogenesis of primary FAPs from control muscles was enhanced when subjected to siRNA Smn1 knockdown. Together, these findings demonstrate that reduced Smn activity potentiates intrinsic adipogenic bias in FAPs that may contribute to pathological fat deposition in SMA muscle."

Journal • Preclinical • CNS Disorders • Fibrosis • Genetic Disorders • Immunology • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Transplantation • SMA4 • SMN1

Risdiplam Impact in Treatment Naïve and Non-Naïve Pediatric and Adult Patients With Spinal Muscular Atrophy. (PubMed, Eur J Neurol) - "This study fills Asian real-world data gaps, stresses the importance in monitoring in severe SMA, and underscores the need for larger, long-term safety and efficacy studies."

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

Onasemnogene Abeparvovec in Type I Spinal Muscular Atrophy: 24-Month Follow-Up From the Italian Registry. (PubMed, Ann Clin Transl Neurol) - "Age and baseline motor functional status significantly influence outcomes; however, substantial confounding, particularly the initial treatment, limits the ability to isolate individual effects. Longer follow-up is essential for evaluating therapeutic responses in heterogeneous SMA I populations."

Journal • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Prenatal therapy for SMA using risdiplam (ASGCT 2026) - "Organized by the Prenatal Cell and Gene Therapy Committee."

Gene Therapies

Evaluating effects of risdiplam in adults with spinal muscular atrophy: a monocentric study. (PubMed, ERJ Open Res) - "In these patients, sniff nasal inspiratory pressure is the most effective test to demonstrate effects of pharmacological therapy. https://bit.ly/3Wk2MCU."

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

EVIDENCE BASE FOR JOINT CLINICAL ASSESSMENT: A CLINICAL SYSTEMATIC LITERATURE REVIEW OF OAV101 IT AND COMPARATORS FOR SPINAL MUSCULAR ATROPHY (ISPOR 2026) - "No head-to-head RCTs were identified for SMA DMTs including nusinersen, risdiplam, and onasemnogene abeparvovec. Studies identified in this SLR, combined with the evidence hierarchy applied, comprise a foundational high-quality evidence base. This evidence was used to assess the feasibility of conducting comparative effectiveness analyses amongst comparator SMA DMTs for the JCA of OAV101 IT."

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

FEASIBILITY OF INDIRECT TREATMENT COMPARISONS FOR OAV101 IT IN SPINAL MUSCULAR ATROPHY (ISPOR 2026) - "Based on clinical evidence for SMA DMTs, ITCs were feasible for OAV101 IT versus nusinersen and risdiplam in both DMT-naïve and -experienced populations aged ≥2 years. However, an ITC of OAV101 IT versus OAV101 IV was not feasible. These findings confirm that comprehensive feasibility assessments are necessary for informing evidence generation strategies across often wide-ranging populations and outcomes of interest to JCA and other HTAs."

Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Adult SMA REACH: A UK clinical network and real-world data collection study for adults living with spinal muscular atrophy. (PubMed, J Neuromuscul Dis) - P | "In recent years, the treatment landscape in the SMA setting has rapidly evolved with Nusinersen and Risdiplam receiving conditional approval via a Managed Access Agreement (MAA) in the UK. In this paper we describe the complexity of establishing such a study and clinical network including considerations for adapting this model to other disease areas. Further information on the Adult SMA REACH data collection study and clinical network can be found on the website (https://adultsmareach.co.uk/) and ClinicalTrials.gov (NCT06978985, https://clinicaltrials.gov/study/NCT06978985)."

Journal • Real-world evidence • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Preventing spinal muscular atrophy through the national premarital screening program in Türkiye: an economic comparison with treatment costs. (PubMed, Turk J Med Sci) - "The annual costs of SMA treatment (with nusinersen and risdiplam) and the costs associated with carrier screening, genetic counseling, and IVF with PGT were compared. The SMA premarital carrier screening and prevention program in Türkiye significantly reduces healthcare expenditures and disease burden. Primary prevention through carrier screening is associated with lower overall costs than long-term treatment, offering both economic and social advantages for public health policy."

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

Serial Compound Muscle Action Potential to Assess Improvement Following Gene Modifying and Replacement Therapies in Spinal Muscular Atrophy (AAN 2026) - "Serial median-APB and fibular-TA amplitudes are sensitive biomarkers able to assess motor-unit maturation following gene-replacement-therapy in SMA patients beyond infancy, while CHOP-INTEND scores plateaued at six months of life. Further analysis, correlating serial CMAP data with highest motor milestone achieved and its value in guiding treating teams to start combinatorial therapies (i.e. risdiplam, onasemnogene-abeparvovecxioi, nusinersen) are being explored."

Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Priced out of Progress: Neurology Innovation Beyond Patient Reach (AAN 2026) - "In South Asian LMICs, their entry has been delayed, and prices far exceed median household income, limiting accessibility and clinical integration.Design/ We audited six therapies (ocrelizumab, risdiplam, onasemnogene abeparvovec, lecanemab, donanemab, tenecteplase)... Recent neurological breakthroughs remain inaccessible for most LMIC patients. When present, therapies are limited to a few tertiary hospitals and remain unaffordable relative to household means. Closing this gap requires LMIC-specific reforms: pooled procurement, tiered pricing, subsidy schemes for time-critical drugs, and hub-and-spoke expansion neurological services."

Clinical • Cardiovascular

Outcomes of combination therapy with nusinersen, onasemnogene abeparvovec, and risdiplam over 3.5 years in a patient with prenatally diagnosed spinal muscular atrophy type 0: A case report. (PubMed, Brain Dev) - "Early intervention with combined use of disease-modifying therapies may be beneficial for patients with severe spinal muscular atrophy phenotypes. However, since evidence of efficacy and safety of combination therapy is still lacking, great caution should be paid to this treatment strategy, taking the patient's clinical status into account."

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

Spinal Muscular Atrophy-Survivorship and Care in a New Therapeutic Landscape. (PubMed, Pediatr Neurol) - "With improved function and survival, new questions are emerging around the role of combining multiple SMN-restoring therapies or SMN-restoring therapies with newer therapeutic agents targeting other pathways such as neuromuscular transmission or muscle growth. Additionally, with the earlier initiation of SMN-restoring disease-modifying therapies, the assessment of long-term treatment durability, motor function attained and retained, neurodevelopment, and potential emerging phenotypes or symptoms in individuals living with SMA will need to be explored."

Journal • Review • Amyotrophic Lateral Sclerosis • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1

Retinal Screening for Risdiplam-Related Toxicity in Infants With Presymptomatic Spinal Muscular Atrophy: Evidence for Transient Cystoid Macular Edema as a Possible Developmental Variant. (PubMed, J Pediatr Ophthalmol Strabismus) - "However, the small sample size and absence of a comparison group mean the data are insufficient to determine whether these changes are physiologic, associated with SMA, or treatment related. These findings highlight the need for normative neonatal OCT data to guide interpretation of early retinal findings and support the cautious hypothesis that inner retinal cystic changes may represent a physiologic stage of postnatal development."

Journal • Genetic Disorders • Macular Edema • Movement Disorders • Muscular Atrophy • Ophthalmology • Rare Diseases

JAV-RARAS -HEALTHCARE INFRASTRUCTURE AS A COST DRIVER: A COST-INTEGRATED SYSTEM ANALYSIS OF TREATMENT ACCESS AND ECONOMIC BURDEN FOR SPINAL MUSCULAR ATROPHY IN BRAZIL (ISPOR 2026) - "Regional drug utilization and cost data for Nusinersen and Risdiplam (2024-2025) from DATASUS were linked to facility locations via geospatial analysis to assess cost disparities. Brazil has an estimated 1,300-2,500 SMA patients. Infrastructure inequity is a primary cost driver in SMA management. The absence of Reference Centers forces reliance on high-cost therapies, converting clinical access barriers into substantial economic burdens. Policy reforms must prioritize equitable infrastructure development, including expanding Reference Center networks and standardizing protocols to facilitate oral therapy access, to improve patient outcomes and ensure the fiscal sustainability of rare disease care."

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

BUDGET IMPACT AND COST-EFFECTIVENESS OF RISDIPLAM VERSUS NUSINERSEN FOR SPINAL MUSCULAR ATROPHY IN PANAMA'S MINISTRY OF HEALTH: REAL-WORLD EVIDENCE AND ECONOMIC EVALUATION (ISPOR 2026) - "In Panama's MINSA, risdiplam offers budget savings of $860,424 over 5 years versus nusinersen while eliminating invasive procedures and achieving favorable clinical outcomes. These real-world findings support risdiplam as a cost-saving treatment option for resource-limited settings managing ultra-rare diseases."

Clinical • Cost effectiveness • HEOR • Real-world • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

JAV-RARAS - GAPS BETWEEN GUIDELINE AND PRACTICE: AN ANALYSIS OF ADHERENCE TO NATIONAL PROTOCOLS IN MUCOPOLYSACCHARIDOSIS TYPE VI (MPS VI), TYPE IVA (MPS IVA), AND SPINAL MUSCULAR ATROPHY (SMA), USING REAL-WORLD PROCESS DATA (ISPOR 2026) - "Care journeys were mapped via TDABC for MPS VI (3 centers, 33 patients), MPS IVA (3 centers, 16 patients), and SMA (3 treatment lines in 3 centers, 42 patients across 3 treatment lines: nusinersen, risdiplam, onasemnogene abeparvovec)... Brazilian centers align with PCDTs in core aspects but often expand care with additional resources, resulting in longer, more complex journeys. This real-world practice, alongside the overwhelming cost concentration on innovative drugs ({>99%} for MPS VI and SMA), highlights the need for PCDT updates that reflect comprehensive care and sustainable economic planning."

Adherence • Clinical • Real-world • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

Neuromuscular Junction Evaluation Using Stimulated Jitter Analysis in Children with Spinal Muscular Atrophy (AAN 2026) - "Disease-modifying therapies included nusinersen (n=5), risdiplam (n=6), and onasemnogene-abeparvovec (n=6), with some receiving combination or sequential therapies... Stim-JA quantifies NMJ abnormalities in children with SMA. Increased mean jitter, abnormal fibers, and blocking correlated with disease severity measured by motor milestones, and CHOP-INTEND. Stim-JA can serve as an objective biomarker for therapies targeting NMJ dysfunction in SMA."

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

Risdiplam as Effective Bridge Therapy Before Gene Replacement in Presymptomatic Infants with SMA (AAN 2026) - "Temporary contraindications such as anti–AAV9 seropositivity or low body weight may delay gene therapy initiation in SMA. Bridging treatment with risdiplam can maintain motor function and allow safe transition to gene therapy once contraindications resolve. These cases highlight the importance of individualized therapeutic strategies in optimizing outcomes for infants with SMA."

Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Treatment of SMA in a Preterm Infant with Elevated Anti-AAV9 Antibody Titers: A Case Report (AAN 2026) - "Objective: To present a case of the treatment of a preterm infant with spinal muscular atrophy (SMA) using risdiplam bridging to onasemnogene abeparvovec (Zolgensma)Background: SMA type 1 is the most common monogenic cause of death in infancy...Intrathecal nusinersen is under consideration... Management of SMA in premature infants is complex, with no standardized approach. This case highlights the challenges of timing therapy and the potential discordance between clinical scales and neurophysiological measures early after therapy. Further research comparing in utero treatment with early postnatal therapy is crucial to determine optimal strategies for improving outcomes in preterm infants with SMA."

Case report • Clinical • Prematurity • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Beyond Motor Function in Adults With Spinal Muscular Atrophy (SMA): A Systematic Literature Review of Real-world Outcomes With Risdiplam (AAN 2026) - P2 | "Results support the potential for risdiplam RW effectiveness in maintaining or improving motor and non-motor function and quality of life in adults with SMA. Long-term studies are needed to provide further insights."

Clinical • Real-world • Real-world evidence • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Risdiplam and Nusinersen in Adults With Spinal Muscular Atrophy: Single Center Study of Changes in Functional Status and Barriers to Care (AAN 2026) - "Nusinersen and risdiplam were associated with stable/modestly improved motor outcomes in adult SMA patients. A subset of patients showed continued improvement after switching therapies, suggesting potential benefit of sequential treatment. Despite the single-center sample, trends underscore the importance of longitudinal follow-up and addressing barriers to care."

Clinical • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1

Long-term Efficacy and Safety of Risdiplam in Adults With 5q Spinal Muscular Atrophy (SMA): A Large Prospective Multi-centre Observational Study (AAN 2026) - "SMA patients on Risdiplam showed significant improvements in several motor outcome measures compared to the baseline, whilst others remained stable over the follow up period of 42 months. Several subgroup analysis and change over time in various motor outcome measures will be presented in detail along with PROMs data. There was no new safety signals identified.Our prospective, observational, long-term (42 months) data provide substantial real-world evidence, that describes the efficacy and safety of Risdiplam in a large cohort of UK adult SMA patients."

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

Real-world Motor Function Outcomes with Risdiplam in Types 2 and 3 Spinal Muscular Atrophy (SMA): A Systematic Literature Review and Meta-analysis (AAN 2026) - P2 | "Findings will provide further insights into the RW effectiveness of risdiplam."

Real-world • Real-world evidence • Retrospective data • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Rainbowfish: A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2029 ➔ Mar 2027

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