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

Comparative Analysis of SMN2 Splicing Activity and Protein Production Following In Vitro Treatment with the Generic Risdiplam Drug Vapromin® and the Reference Drug Evrysdi®. (PubMed, Biomedicines) - " This study experimentally confirmed that the in vitro biological activity of the generic drug Vapromin® is comparable to that of Evrysdi® (Roche, Basel, Switzerland). Further research should be conducted to confirm bioequivalence between the two products."

Journal • Preclinical • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Real-World Treatment Patterns in Patients with Spinal Muscular Atrophy Receiving Multiple Disease-Modifying Therapies. (PubMed, Adv Ther) - "Following widespread NBS, OAV had the highest utilization among patients age ≤ 2 years as first or second DMT after nusinersen or risdiplam. Use of a second DMT type was lowest among patients who initiated OAV."

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

Serum circulating cell-free messenger RNA profile response to risdiplam treatment in adult patients with late-onset spinal muscular atrophy. (PubMed, Brain Commun) - "A separate exploratory subgroup of patients switching from nusinersen to risdiplam (n = 7) was analysed at comparable time points. Serum ccfmRNA profiles distinguish adult loSMA from controls and capture risdiplam-associated molecular responses. These findings support the concept that serum ccfmRNA profiling may provide a useful exploratory framework for studying disease-associated and treatment-associated molecular changes in adult loSMA."

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

Pharmacovigilance and network toxicology analysis of risdiplam-associated adverse events in pediatric patients with spinal muscular atrophy. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Molecular docking confirmed stable binding (- 10.1 to - 8.6 kcal/mol). Risdiplam demonstrates a generally acceptable long-term safety profile in clinical practice, yet vigilant monitoring of respiratory, infectious, gastrointestinal, and renal adverse events remains essential to optimize the benefit-risk balance."

Adverse events • Journal • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Nephrology • Pediatrics • Pneumonia • Rare Diseases • Renal Calculi • Respiratory Diseases • CASP3 • HDAC1 • PDGFRA • SMN2

Spinal muscular atrophy as a blueprint for precision therapy in neuromuscular disease. (PubMed, Expert Rev Mol Med) - "The evolution of SMA therapies has transformed neurogenetics. Clinical benchmarks have successfully shifted from reactive, symptomatic management to proactive, molecularly targeted precision medicine."

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

Case Report: Presymptomatic risdiplam in preterm monozygotic twins with co-occurring spinal muscular atrophy and tuberous sclerosis complex. (PubMed, Front Genet) - "These findings also highlight the importance of comprehensive genetic evaluation in infants with SMA who present with atypical neuroimaging or neurological features. Longer-term follow-up is needed to clarify safety, efficacy, and optimal integrated management strategies in patients with complex genetic comorbidities."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2 • TSC1

Spinal Muscular Atrophy, Sleep-Disordered Breathing, and the Effects of Disease-Modifying Therapies: A Narrative Review. (PubMed, Pediatr Neurol) - "Much of existing medical literature regarding SDB in SMA and the impact of DMTs is derived from studies of small sample sizes, abstracts, and varying methodologic rigor. To advance our understanding of DMTs' effects on the management and potential prevention of SDB in SMA, rigorous, multicenter, blinded prospective cohort studies with large sample sizes are essential. Furthermore, specific attention should be directed toward assessing the superiority of single-agent therapy versus combination therapy in mitigating the morbidity associated with SDB in SMA."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Obstructive Sleep Apnea • Rare Diseases • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Respiratory Trajectories in Children with Type I and II Spinal Muscular Atrophy in the Era of Disease modifying Therapies (ERS 2026) - "First line treatment was Nusinersen for 22 (73%), Risdiplam for 3 (10%) and Onasemnogene Aberparvovec for 5 (17%) patients... Respiratory function in children with type I and II SMA treated by DMTs remains severely impaired, with a need for intensive care, airway clearance devices and early initiation of NIV. Early respiratory interventions may stabilize respiratory function and improve outcomes."

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

Consensus on gene therapy for spinal muscular atrophy in Taiwan. (PubMed, J Formos Med Assoc) - "The advent of three FDA-approved disease-modifying therapies-onasemnogene abeparvovec, nusinersen, and risdiplam-has markedly improved therapeutic prospects...This consensus recommends incorporating SMA into the newborn screening program for early diagnosis and prompt treatment, and emphasizes that gene therapy should be evaluated based on SMN2 copy number and clinical condition. Presymptomatic treatment is critical for optimal motor outcomes, and multidisciplinary care teams are essential for comprehensive long-term management."

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

UK SMA patient registry: a 3-year patient-reported outcome measures study supporting the drug appraisal of Nusinersen and Risdiplam in spinal muscular atrophy. (PubMed, J Neurol Sci) - "The study demonstrated the successes of implementing PROMs to support MAA data collection and marked an important milestone for patients' voices to contribute to SMA therapy evaluation through a patient registry. The study data emphasises that patient-reported data complements and offers an alternate perspective to clinical real-world data."

Journal • CNS Disorders • Depression • Genetic Disorders • Mood Disorders • Movement Disorders • Muscular Atrophy • Psychiatry • Rare Diseases

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=97 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=259 ➔ 97

Enrollment change • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

WeSMA: Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P4 | N=403 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Dec 2026 ➔ Oct 2026 | Trial primary completion date: Dec 2026 ➔ Oct 2026

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

Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions. (PubMed, Front Mol Med) - "In recent years, three FDA-approved disease-modifying therapies, nusinersen, risdiplam, and onasemnogene abeparvovec, have improved the quality of life for patients with SMA and have eased the management of associated symptoms. However, unmet needs remain as comorbidities become increasingly apparent in the era of disease-modifying therapies. Despite the remarkable progress achieved over the past decade, continued research is essential to further improve the quality of life, clinical outcomes, and standard of care for individuals living with SMA."

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

Respiration during sleep in children with spinal muscular atrophy type 2 and 3, treated with nusinersen or risdiplam. (PubMed, Sleep Med) - "Over the study period, DMTs were associated with stabilization or improvement of sleep-related respiration in both SMA type 2 and 3. This included reduced SDB in type 2 and improved TAA in type 3, with no evidence of respiratory decline."

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

Real-world pharmacoclinical implementation of risdiplam under a national SMA protocol: A hospital pharmacy registry-based case series. (PubMed, Pak J Pharm Sci) - "Risdiplam was used appropriately in accordance with protocol criteria. Registry incompleteness, rather than clinical deviation, was the main limitation and standardized data capture is essential for real-world evaluation."

Journal • Real-world evidence • Retrospective data • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

From Genes to Function: Clinical Experience with the Effectiveness and Safety of Risdiplam and Nusinersen in Spinal Muscular Atrophy. (PubMed, Iran J Child Neurol) - "No severe side effects were experienced and only a few patients reported headaches, and backaches following Nusinersen. both Risdiplam and Nusinersen led to significant improvements in motor function; however, based on cost-effectiveness considerations, we recommend Risdiplam."

Journal • Back Pain • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases • SMA4 • SMN1 • SMN2

Successful administration of glecaprevir/pibrentasvir via percutaneous endoscopic gastrostomy in a pediatric patient with chronic hepatitis C and spinal muscular atrophy receiving risdiplam. (PubMed, Clin J Gastroenterol) - "We report a case of a 14-year-old dysphagic patient with SMA, receiving Risdiplam, who was successfully treated with crushed GLE/PIB administrated via PEG. The patient achieved a sustained virologic response (SVR) 12 weeks after the end of therapy, without significant adverse effects, and no drug interactions were observed during the course of treatment."

Journal • Gastrointestinal Disorder • Genetic Disorders • Hepatitis C • Infectious Disease • Inflammation • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases

Gene therapy benefits in a small cohort of symptomatic 5q spinal muscular atrophy patients and real world pediatric outcomes. (PubMed, J Pediatr (Rio J)) - "In this small and heterogeneous cohort, gene therapy after symptom onset was primarily associated with clinical stabilization and limited motor milestone acquisition, while established respiratory and nutritional impairments persisted. These results emphasize the need for realistic treatment counseling and reinforce the importance of early diagnosis."

Journal • Real-world evidence • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases • Respiratory Diseases

Therapeutic strategies for spinal muscular atrophy: the history and future perspective. (PubMed, Front Hum Neurosci) - "The FDA approval of nusinersen, an antisense oligonucleotide targeting SMN2 splicing, in 2016 marked the first disease-modifying therapy, followed by the gene replacement therapy onasemnogene abeparvovec in 2019 and the orally administered small-molecule splicing modifier risdiplam in 2020...Finally, we address future directions encompassing precision medicine, next-generation gene editing, and biomarker-driven trial design. While SMA has been transformed from a fatal childhood disorder to a treatable condition, a definitive cure for all patients remains the goal of ongoing and future research."

Journal • Review • CNS Disorders • Gene Therapies • Genetic Disorders • Inflammation • Movement Disorders • Muscular Atrophy • Rare Diseases • NEFL • PLS3 • PTEN • SMA4 • SMN1 • SMN2

Generic risdiplam and global spinal muscular atrophy care: opportunities and challenges in low- and middle-income countries (LMICs). (PubMed, Neuromuscul Disord) - No abstract available

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

Longitudinal Dosing Patterns and Treatment Costs Among Patients with Spinal Muscular Atrophy Initiating Nusinersen and Risdiplam. (PubMed, Adv Ther) - P | "Nusinersen and risdiplam persistence declined over time. Among patients remaining on their index therapy, both treatments had high long-term costs, highlighting the substantial and ongoing financial burden of chronic SMA therapies and the need for real-world evidence to inform healthcare planning."

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

Motor function score changes in severe 5q spinal muscular atrophy during risdiplam treatment: an observational longitudinal nationwide cohort study. (PubMed, EClinicalMedicine) - "Motor function changes during treatment with SMN2 splicing modifiers (i.e., nusinersen and risdiplam) have been shown in randomised clinical trials in infants, children and young adults with SMA, but not in severely affected adult patients, for whom risdiplam is often the only treatment option. The majority of patients report improvement or stabilisation in motor function and overall wellbeing. None."

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

A Study of Risdiplam in Participants With Type I and Type II Spinal Muscle Atrophy (SMA) (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Muscular Atrophy

Spinal Muscular Atrophy in Adult Neurology Services in India. (PubMed, Clin Genet) - "Three SMA patients received risdiplam. Our cohort highlights the diagnostic challenges of adult SMA and supports a genetics-first approach. Early genetic confirmation shortens diagnostic delay, reduces misclassification and helps eligible patients benefit as disease-modifying therapies become more affordable in resource-limited settings."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Myositis • Pediatrics • Rare Diseases

Pediatric Extrapolation in Neuropsychiatric Drug Development: Leveraging Pharmacokinetic and Pharmacodynamic Strategies to Facilitate FDA Approvals. (PubMed, Clin Pharmacol Ther) - "Case examples spanned broad age ranges, from mechanistically informed neonatal applications utilizing enzyme maturation modeling (risdiplam) to adolescent populations where adult dosing regimens proved adequate (brexanolone, nipocalimab). Additionally, pharmacodynamic biomarkers were pivotal in pediatric extrapolation of eculizumab and nipocalimab efficacy for the treatment of generalized myasthenia gravis, highlighting promising future directions for the field. These cases demonstrate how achieving comparable pharmacokinetics and, when necessary, pharmacodynamics profiles between adult and pediatric populations can support efficient regulatory approval without dedicated pediatric efficacy studies. The regulatory pathways established for select neuropsychiatric indications provide a compelling framework for expanding extrapolation approaches to other therapeutic areas."

FDA event • Journal • PK/PD data • Review • CNS Disorders • Myasthenia Gravis • Pediatrics • Psychiatry