Zolgensma (onasemnogene abeparvovec-xioi) / Novartis, REGENXBIO - LARVOL DELTA

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

Securitization as a means to pay for cell and gene therapies for orphan diseases: a simulation study. (PubMed, Gene Ther) - "Using securitization techniques combined with long-term performance-based annuities, we demonstrate that in the case of the gene therapy Zolgensma, this mechanism is effective at mitigating concerns over value and affordability for payers. In summary, our proposal for financing cell and gene therapies creates a viable incentive for developers, while also balancing long-term effectiveness and budget impact concerns from payers and access challenges for patients."

Journal • Gene Therapies

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

Compound Muscle Action Potentials as Potential Motor Outcome Predictors of Spinal Muscular Atrophy in Children with Onasemnogene Abeparvovec-xioi Gene Therapy (AAN 2026) - "Reduced motor CMAP amplitudes were able to pick motor neuron loss and diseaseseverity in NBS positive pre-symptomatic SMA babies. Abnormal CMAP data precedes reduction in weight or CHOP-INTEND. On several occasions, the abnormal CMAP results were available prior to confirmatory genetic testing and SMN2 copy number, highlighting the value of pre-confirmatory neurophysiological testing."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

PRICE ANALYSIS OF GENE THERAPIES AUTHORIZED BY THE U.S. FOOD AND DRUG ADMINISTRATION (ISPOR 2026) - "The inflation-adjusted WAC (adj-WAC) ranged from $253,121 (revakinagene taroretcel) to $4,395,213 (atidarsagene autotemcel)...Tisagenlecleucel had different prices for two indications and onasemnogene abeparvovec for two routes of administration/patient populations... When adjusted for inflation, prices remained relatively constant over time. Prices varied depending on therapeutic class, patient population, and duration of therapy. Gene therapies had similar WAC and ASP."

Gene therapy • Gene Therapies

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

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

VALUE-BASED PURCHASING ARRANGEMENTS IN MEDICAID: A TARGETED LITERATURE REVIEW (ISPOR 2026) - "States' Medicaid programs have increasingly explored outcome-based agreements, with a steady increase over recent years. No new subscription-based purchasing arrangements have been implemented since 2019, suggesting less enthusiasm for this type of VBP. Gene therapies are the most frequently included products in outcome-based agreements."

Medicaid • Reimbursement • Review • US reimbursement • Gene Therapies • Hepatitis C • Hepatology • Infectious Disease • Inflammation

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

Therapeutic Efficacy and Safety of Onasemnogene Abeparvovec Gene Therapy for Spinal Muscular Atrophy Type 1: Updated Systematic Review with Meta-analysis (AAN 2026) - "Onasemnogene improves chances of survival in SMA1 patients, especially if patients had previous treatment, significantly improves motor abilities, and is generally tolerable."

Gene therapy • Retrospective data • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Thrombocytopenia

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

Low-Dose AAV9-SMN1 with CNS-Selective Expression Delivers Efficacy and Favorable Safety in Spinal Muscular Atrophy. (PubMed, Mol Ther) - P=N/A | "Treatment-related adverse events were largely transient and manageable, with no high-grade drug-related hepatotoxicity observed. SKG0201's design reduces the viral dose requirement while optimizing CNS target engagement, suggesting an improved therapeutic index for SMA gene therapy."

Journal • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1

STELLAR-2: A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec (clinicaltrials.gov) - P3 | N=42 | Not yet recruiting | Sponsor: Biogen

New P3 trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • Plasma NfL • SMN2

Comparison of Nusinersen Monotherapy Versus Combination Therapy With Nusinersen and Onasemnogene Abeparvovec in Spinal Muscular Atrophy Type 1 Patients With Two SMN2 Copies: A Multicenter Study From Türkiye. (PubMed, Muscle Nerve) - "Early treatment is the main determinant of outcomes, while combination therapy shows no clear advantage over monotherapy. Larger prospective studies are needed to clarify the role and timing of combination therapy."

Clinical • Journal • Monotherapy • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Skeletal muscle in spinal muscular atrophy: Critical insights from pathogenesis to therapeutic strategies. (PubMed, Neurobiol Dis) - "Furthermore, despite the revolutionary therapeutic effects of nusinersen, risdiplam, and onasemnogene abeparvovec, skeletal muscle abnormalities remain frequent, particularly in symptomatic patients, highlighting the need for muscle-directed therapies...Work with neuromuscular models and stem cell-derived organoids continues to shed light on the SMN-mediated interactions between muscle and nerve. Collectively, these findings indicate that skeletal muscle is both a key driver of SMA pathology and an essential target for novel therapies."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Summary of Research: Risdiplam Treatment Following Onasemnogene Abeparvovec in Individuals with Spinal Muscular Atrophy: A Multicenter Case Series. (PubMed, Adv Ther) - "This study may help to improve understanding of the potential risks and benefits of using risdiplam treatment after OA treatment in children with SMA. Further studies including more children are necessary."

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

Patient reported outcome measures in spinal muscular atrophy and duchenne muscular dystrophy: review of instruments and their inclusion in clinical and regulatory processes. (PubMed, Neurol Sci) - "Despite the availability of PROMs, ObsROMs, and CROMs for SMA and DMD, their use in clinical trials and regulatory documents is limited and inconsistent. Greater standardization and systematic inclusion of these measures are needed to support patient-centered drug development and evaluation."

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

Longitudinal assessment of respiratory status utilising the amended Great Ormond Street Respiratory Score in treated spinal muscular atrophy type 1 children. (PubMed, Neuromuscul Disord) - "In total, 32 first initiated nusinersen therapy, 16 first initiated onasemnogene abeparvovec and 11 first initiated risdiplam therapy...Those treated after one year show worse scores but stabilise. Despite the switching between disease modifying treatments, the Great Ormond Respiratory Score is a useful and easy-to-use clinical outcome measure which can demonstrate change in respiratory status over longitudinal review."

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

Five-year disease-modifying therapeutic experience of 102 Chinese paediatric 5q-spinal muscular atrophy: a retrospective analysis. (PubMed, Brain Commun) - "Moreover, longer diagnostic to treatment intervals were significantly and inversely associated with motor function gains and directly associated with higher complication rates. This retrospective study confirms the effectiveness of nusinersen and risdiplam for 5q-spinal muscular atrophy and highlights the critical importance of early initiation of DMTs."

Journal • Retrospective data • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Musculoskeletal Diseases • Orthopedics • Pediatrics • Rare Diseases • Respiratory Diseases • IGF1

Fusionless spinal surgery in children with spinal muscular atrophy type 1 with bipolar system: a preliminary communication. (PubMed, J Pediatr Orthop B) - "While recent therapies such as nusinersen and onasemnogene abeparvovec have improved survival and ventilation-free time, affected children develop pelvic asymmetry and progressive spinal deformity, impairing the sitting position...T1-S1 spinal length increased from 27.1 ± 1.8 to 30.9 ± 2.0 cm (P < 0.001), and thoracic width from 167.4 ± 12.0 to 181.5 ± 15.8 mm (P = 0.0017). The bipolar system appears to be a safe and effective surgical option for managing scoliosis in SMA type 1 patients, achieving significant correction of spinal and pelvic parameters without complications."

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

Circulating Tau Profiles in Pediatric and Adult Patients with Spinal Muscular Atrophy. (PubMed, medRxiv) - "Circulating Tau, particularly pTau-262, may serve as a disease-relevant biomarker in adult SMA, while pediatric profiles appear more heterogeneous. Transient Tau elevations after gene therapy may reflect acute neuronal vulnerability and warrant further investigation."

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

Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials (clinicaltrials.gov) - P3 | N=175 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2030 ➔ Feb 2031 | Trial primary completion date: Jun 2030 ➔ Sep 2030

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