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

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

Safety and effectiveness of risdiplam in adults with spinal muscular atrophy: a systematic review. (PubMed, J Neurol) - "Risdiplam shows a favorable safety profile and provides both disease stabilization and multidimensional benefits across all functional phenotypes in adults with SMA, although further longitudinal studies using standardized outcome measures are needed to clarify its long-term impact."

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

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

Comprehensive Risdiplam Synthesis Overview: From Cross-Coupling Reliance to Complete Palladium Independence. (PubMed, Molecules) - "Recently, our group has also developed and introduced efficient, scalable manufacturing routes for the preparation of the target substance and the key intermediates of its synthesis. This mini-review systematically analyzes a plethora of risdiplam assembly strategies and synthetic approaches, covering developments from 2013 to the present."

Journal • Review • 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

Risdiplam: A Small Molecule mRNA Splice Modifier Approved to Treat SMA Disease. (PubMed, Toxicol Pathol) - "Yet, the nonclinical development of risdiplam was marked by toxicological challenges requiring new strategies and approaches, which ultimately translated into clinical success. This minireview covers key aspects of the nonclinical development of risdiplam, particularly focusing on its toxicological characterization and histopathological features in animal studies."

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

Comment on "Survival motor neuron protein is the optimal biomarker for evaluating the risdiplam treatment". (PubMed, Brain Dev) - No abstract available

Biomarker • Journal

Time-dependent SMN2 splicing modulation reveals ciliary gene dysregulation as a novel therapeutic target in SMA spinal cord organoids (Neuroscience 2025) - "Our organoid model recapitulated key disease features, including altered GABAergic neuron morphology, increased astrogliosis, and impaired network activity as measured by multielectrode array recordings.Treatment with RO7021707, a Risdiplam-like SMN2 splicing modifier, demonstrated maximal therapeutic efficacy when initiated at day 45 of differentiation—a timing that corresponded with peak SMN protein restoration and functional recovery...Across treatment timepoints, we consistently observed upregulation of 3 genes and downregulation of 43 genes, with significant enrichment in ribosomal organization and oxidative phosphorylation pathways.These findings establish ciliary dysfunction as a novel pathogenic mechanism in SMA and demonstrate that precise timing of SMN restoration is critical for achieving optimal therapeutic outcomes. Our results provide new mechanistic insights into the effects of treatment timing and identify ciliary function as a potential therapeutic..."

CNS Disorders • Movement Disorders • Muscular Atrophy • SMN2

Using Expert Consensus to Expand Access in Rare Disease Populations: Generating Evidence for Patients With Permanently Ventilated Spinal Muscular Atrophy (ISPOR-EU 2025) - "Disease-modifying therapies (DMTs), including risdiplam, are available in England under Managed Access Agreements (MAAs)... For rare disease populations, such as SMA-PV, Delphi consensus processes can provide alternative methodologies for generating guidance where robust clinical evidence generation is challenging. It is hoped these insights could support payer decision-making, enhance access to DMTs, guide clinical practice concerning DMT use and improve outcomes for this underrepresented group. While only UK experts were consulted, it is hoped these outcomes can guide global clinical practice."

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

Comparing the Time to Reimbursement of the Orphan Drug Evrysdi in Turkiye vs. Euro-5 Markets (ISPOR-EU 2025) - "Preliminary observations suggest that Evrysdi not only experienced delayed market entry by almost three years but also late reimbursement in Turkiye compared to the EURO-5 markets. This is mainly due to the SGK's strict criteria relating to the reimbursement of high-cost therapies. Despite this, the quicker time to reimbursement in Turkiye than three top EU markets is a sign that orphan drugs are being prioritized for reimbursement to improve patient access."

Reimbursement • US reimbursement • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

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

Efficacy and safety of risdiplam in adults with 5q-associated spinal muscular atrophy: a nationwide observational cohort study in Austria. (PubMed, EClinicalMedicine) - "These findings support the long-term use of risdiplam in adults with SMA and help close a critical evidence gap in this underrepresented population. This study was financially supported by F. Hoffmann-La Roche Ltd."

Journal • Observational data • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • 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

ACUTE LYMPHOBLASTIC LEUKAEMIA IN A CHILD WITH SPINAL MUSCULAR ATROPHY (SMA) TYPE 3 ON GENE THERAPY CAUSING A DILEMMA FOR LEUKAEMIA TREATMENT. (SIOP 2025) - "Risdiplam is the first oral gene therapy which prevents damage caused by faulty SMN1 gene by replicating SMN2 proteins, identical to functional SMN1 proteins...Furthermore, Acute Leukaemia treatment is based on a steroid backbone of Dexamethasone, known to cause proximal myopathy, when used with Vincristine can cause significant neuromuscular difficulties by causing peripheral neuropathy which was a challenge in a child already having functional difficulties due to SMA type 3, requiring treatment modification...Hence planned for personalised therapy, with Blinatumomab consolidation followed by 2 years of Maintenance therapy... This case emphasises the role of MDT and interdisciplinary coordination to effectively manage patients with complex background."

Clinical • Gene therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Gene Therapies • Genetic Disorders • Hematological Malignancies • Leukemia • Movement Disorders • Muscular Atrophy • Myositis • Rare Diseases • SMA4 • SMN1 • SMN2

Spinal muscular atrophy in India: Patient journey, access to care, treatment barriers, and strategic recommendations: Insights from experts. (PubMed, J Neuromuscul Dis) - "This review provides insights from the expert opinions of Indian pediatricians, neurologists, geneticists, pediatric neurologists, and pediatric pulmonologists on the burden of SMA, diagnosis and management practices, importance of a multidisciplinary approach, challenges faced in SMA care in India, and strategies to overcome these challenges."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Orthopedics • Pediatrics • Rare Diseases

A Chemically Induced CRISPR/dCas13FCPF Platform for Precise and Programmable RNA Regulation. (PubMed, J Med Chem) - "Small-molecule splicing modulators, while clinically validated, like risdiplam, often lack locus specificity, producing off-target effects...The approach generalizes to additional transcripts by crRNA redesign. By coupling CRISPR addressability with dose-sparing chemical action, Chem-CRISPR/dCas13FCPF establishes a proximity-induced, chemically controllable route to precise RNA modulation suitable for therapeutic exploration."

Journal • CNS Disorders • Genetic Disorders • Oncology • SMN2

Summary of Research: Fertility Outcomes in Risdiplam-Treated Male Patients with Spinal Muscular Atrophy: A Multicenter Case Series. (PubMed, Neurol Ther) - "Further research is needed to fully understand the effect of risdiplam on male fertility in the broader SMA population. Findings from this research are relevant to male individuals with SMA, their families, caregivers, patient advocates, and healthcare professionals involved in the diagnosis and treatment of SMA."

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

INTRATHECAL ONASEMNOGENE ABEPARVOVEC (OAV101 IT) FOR TREATMENT-EXPERIENCED PATIENTS WITH SPINAL MUSCULAR ATROPHY (SMA): PHASE 3B, OPEN-LABEL STRENGTH STUDY (WCN 2025) - P1, P3 | "STRENGTH evaluated OAV101 IT safety and efficacy in treatment-experienced SMA patients. STRENGTH (NCT05386680) was a 52-week, phase 3b, single-arm, open-label, multicenter study of OAV101 IT for SMA patients aged 2 to <18 years who were able to sit but not walk independently and who discontinued nusinersen or risdiplam. OAV101 IT safety for treatment-experienced SMA patients in STRENGTH was favorable and consistent with the expected profile. Motor function and caregiver experience results were stable over 52 weeks."

Clinical • P3 data • CNS Disorders • Movement Disorders • Muscular Atrophy

COMPARING THE EFFECTIVENESS OF GENE THERAPIES FOR PEDIATRIC SPINAL MUSCULAR ATROPHY: ZOLGENSMA, SPINRAZA, AND RISDIPLAM (WCN 2025) - "Risdiplam demonstrated strong efficacy with fewer side effects in the first year, while nusinersen was most effective in pre-symptomatic patients. Zolgensma provided rapid early improvements but was associated with higher adverse effects. Long-term studies are necessary to determine sustained efficacy and safety."

Clinical • Gene therapy • CNS Disorders • Movement Disorders • Muscular Atrophy • SMA4 • SMN1

Disease characteristics and treatment status of genetically confirmed spinal muscular atrophy patients: a cross-sectional survey in China. (PubMed, BMC Neurol) - "Patients with different subtypes of SMA are currently experiencing various complications while maintaining good motor function. In the future, there is a significant need for enhanced patient education about DMTs knowledge."

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

A comparison of SMA type 1 outcomes in two brothers treated with disease-modifying and gene therapies (AAP-NCE 2025) - "Other medications used in the treatment of SMA include Spinraza (nusinersen) and Evrysdi (risdiplam) which alter the splicing of the SMN2 gene in order to produce a full length SMN protein.Case Description: Two brothers, both born with SMA 1, received Zolgensma gene therapy... This case demonstrates the importance of early administration of gene therapies such as Zolgensma to optimize developmental outcomes and prevent potential SMA-related complications. It also highlights the importance of early childhood screening for such diseases to allow for early pharmaceutical interventions."

Gene therapy • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2