Itvisma (onasemnogene abeparvovec-brve) / Novartis - LARVOL DELTA

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

ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM) (clinicaltrials.gov) - P4 | N=36 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1

A Study of the Safety and Effectiveness of Onasemnogene Abeparvovec (Zolgensma) Intrathecal Injection in Spinal Muscular Atrophy Patients (clinicaltrials.gov) - P=N/A | N=80 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Indirect Treatment Comparison of OAV101 IT vs Risdiplam and Nusinersen in SMA DMT-Experienced Patients (ICNMD 2026) - P3 | "In the absence of direct head-to-head trials and limited clinical data for DMT-experienced patients, this analysis demonstrates that treatment with OAV101 IT results in comparable improvement in motor milestones relative to nusinersen and risdiplam in SMA DMT-experienced patients. These findings support OAV101 IT as a viable option for SMA DMT-experienced patients who cannot continue or tolerate their current long-term therapy, or prefer to choose a one-time treatment option."

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

Indirect Treatment Comparisons of OAV101 IT vs Risdiplam and Nusinersen in SMA DMT-Naïve Patients (ICNMD 2026) - P2, P3 | "In the absence of direct head-to-head trials for SMA DMTs, these analyses demonstrate that treatment with OAV101 IT results in similar motor milestone improvement and OAV101 IT has a similar safety profile relative to risdiplam and nusinersen in the SMA DMT-naïve patient population. These findings support OAV101 IT as a viable first-line gene-replacement therapy, expanding treatment options for patients with SMA."

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

Novartis today announced that the European Commission (EC) has approved Itvisma (onasemnogene abeparvovec) for the treatment of children two years and older, teens and adults living with 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival motor neuron 1 (SMN1) gene (GlobeNewswire) - "With this approval, Itvisma becomes the first and only gene replacement therapy currently approved for this broad SMA population in the European Union....The approval is based on data from the registrational STEER study, and supportive Phase IIIb STRENGTH and Phase I/II STRONG studies."

EMA approval • Muscular Atrophy

Advancements in Prenatal Diagnosis and Potential Fetal Therapies for Spinal Muscular Atrophy. (PubMed, Clin Ther) - "Early postnatal treatment is currently standard of care for prenatally- and postnatally diagnosed SMA with improvement in outcomes demonstrated following early treatment initiation. Fetal therapy is an emerging research area and shows promise for infants with severe disease in whom motor neuron loss begins in utero. Fetal therapy for SMA is ethically acceptable and likely feasible based on animal studies and a single case report. Ongoing rigorous attention to maternal and fetal safety is of utmost importance as fetal therapy for SMA approaches clinical use."

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

Integrating AAV-SMN1 gene transfer with SMN2 splicing modifiers in spinal muscular atrophy: an updated real-world and trial evidence (ASGCT 2026) - "In older children/adolescents, the phase 3b STRENGTH study of intrathecal onasemnogene in treatment-experienced patients (n=27; age 2-18 years; discontinued nusinersen/risdiplam) met its primary safety/tolerability objective, with adverse events consistent with known risks and no deaths. However, the evidence base remains predominantly observational and short-term; prospective comparative studies with longer follow-up are needed to define optimal sequencing, durability, long-term safety, and clinical value across SMA subgroups. Figure 1- Mechanism of action of three approved SMN-modifying therapies Figure 2- Different approaches for combination therapies of AAV-SMN1 gene transfer with SMN2 splicing modifiers in spinal muscular atrophy"

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

Improving Efficiency in CNS-Directed AAV Delivery: A Comparative Assessment of Freehand and Stereotaxic ICV Injection in Rodents (ASGCT 2026) - "The advantages of moving to CNS-delivery approaches are further underscored by the recent approval of intrathecal Itvisma for spinal muscular atrophy, which is aimed at reducing hepatotoxicity and cardiotoxicity linked to systemic AAV delivery of Zolgensma...Conclusion Overall, both freehand ICV and stereotaxic-guided delivery achieved similar transgene expression and safety profiles. However, the freehand ICV approach offers a faster, less resource-intensive method, making it well suited for high-throughput preclinical screening of candidate AAV vectors."

Preclinical • Cardiovascular • CNS Disorders • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • XBP1

Rational for dose selection for intracerebroventricular AAV9 gene therapy using a CTNNB1 gene therapy model (ASGCT 2026) - P1/2 | "These include AAV9- based therapies for spinal muscular atrophy (SMA), administered intravenously (Zolgensma™) or intrathecally (Itvisma™); an intravenously delivered AAV-based therapy for Duchenne muscular dystrophy (Elevidys™); and AAV2-based therapies delivered subretinally to the eye (Luxturna™) or directly to the brain parenchyma (e.g. intraputaminal administration of Upstaza™)...Prioritizing CNS mRNA expression as an efficacy reference point, while achieving exposures at least two-fold below the NOAEL with supportive safety data, enables ethically justified first-in-human dosing decisions in AAV-based CNS gene therapy trials. This framework is intended to inform dose selection strategies across emerging CNS gene therapy programs beyond a single indication."

First-in-human • Gene therapy • CNS Disorders • Developmental Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases • CTNNB1

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

2026 REVIEW OF GENE THERAPY ACCESS LANDSCAPE (ISPOR 2026) - "The newest gene therapies include Itvisma and Papzimeos, among others. Ultra-high-cost therapies continue to face additional restrictions compared to lower-priced gene therapies. Therapies on market longer generally face less restrictive management, likely due to contracting strategies. Products offering outcomes-based agreements see less restrictive management."

Gene therapy • Review • Gene Therapies

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

On 23 April 2026, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Itvisma, intended for the treatment of spinal muscular atrophy (SMA) (European Medicines Agency) - "The full indication is: Itvisma is indicated for the treatment of 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene in patients 2 years of age and older."

CHMP • Muscular Atrophy

ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM) (clinicaltrials.gov) - P4 | N=36 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2034 ➔ Jun 2032

Real-world evidence • Trial completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1

ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM) (clinicaltrials.gov) - P4 | N=36 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P4 trial • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1

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

Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial. (PubMed, Nat Med) - P3 | "The overall safety findings were acceptable, with similar incidences of AEs, SAEs and AESI in the OAV101 IT and sham groups. Trial registration: ClinicalTrials.gov identifier: NCT05089656 ."

Journal • P3 data • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Novartis today announced that the US Food and Drug Administration (FDA) has approved Itvisma (onasemnogene abeparvovec-brve) for the treatment of children two years and older, teens, and adults living with spinal muscular atrophy (SMA) with a confirmed mutation in the survival motor neuron 1 (SMN1) gene… (PRNewswire) - "The approval of Itvisma is based on data from the registrational Phase lll STEER study and supported by the open-label Phase lllb STRENGTH study."

FDA approval • Muscular Atrophy

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

INTRATHECAL ONASEMNOGENE ABEPARVOVEC (OAV101 IT) FOR PATIENTS WITH SPINAL MUSCULAR ATROPHY (SMA): PHASE 3, RANDOMIZED, SHAM-CONTROLLED, DOUBLE-BLIND STEER STUDY (WCN 2025) - P3 | ": One-time OAV101 IT significantly improved motor function compared with sham control and demonstrated a favorable safety profile for older SMA patients."

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

STEER: Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P3 | N=127 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases

STRENGTH Study (Novartis Press Release) - P3 | N=27 | STRENGTH (NCT05386680) | Sponsor: Novartis Pharmaceuticals | "OAV101 IT demonstrated a favorable safety profile that was consistent with STEER study. The motor endpoint of efficacy, HFMSE, demonstrated stabilization for the overall study population over 52 weeks. The increase from baseline to 52 weeks in HFMSE least squares (LS) total score was 1.05. All patients in the STRENGTH study experienced at least one AE. The most frequent AEs were common cold, pyrexia and vomiting. A total of 13 patients (48.1%) experienced AEs considered to be related to study treatment. No AEs leading to death or study discontinuation were reported."

P3 data • Muscular Atrophy

STEER Study (Novartis Press Release) - P3 | N=127 | STEER (NCT05089656) | Sponsor: Novartis Pharmaceuticals | "Novartis plans to file applications with regulatory agencies in H1 2025...The trial met its primary endpoint of change from baseline to 52 weeks in HFMSE score, with OAV101 IT demonstrating a statistically significant 2.39-point improvement on the HFMSE vs 0.51 points in the sham group (overall difference, 1.88 points; P=0.0074). All secondary endpoints consistently favor OAV101 IT, despite not achieving statistical significance due to the pre-planned multiple testing procedure. The overall incidence of adverse events (AEs), serious AEs (SAEs), and AEs of special interest was similar between both groups."

Filing • P3 data • Muscular Atrophy

STRENGTH: Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam (clinicaltrials.gov) - P3 | N=27 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

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