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

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

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

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

Recent Advance in Disease Modifying Therapies for Spinal Muscular Atrophy. (PubMed, Acta Neurol Taiwan) - "Current three disease modifying drugs, including nusinersen, onasemnogene abeparvovec, and risdiplam, have demonstrated impressive effectiveness in SMA treatment...The development in these therapies has benefited patients with SMA and will potentially provide insight in future drug discovery for other neurodegenerative diseases. Keywords: Adeno-associated viral vector, antisense oligonucleotide, disease modifying therapy, gene therapy, motor neuron disease, spinal muscular atrophy."

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

SKG1201: Liver De-Targeting Vector for Spinal Muscular Atrophy Gene Therapy via Intrathecal Injection (ASGCT 2024) - "Moreover, the adverse events observed after intrathecal injection (IT) of Zolgensma in Type II SMA patients in the recent STRONG trial were consistent with what noticed after its intravenous (IV) delivery...Currently both nonclinical toxicology and biodistribution studies are being planned to evaluate its safety and biodistribution in cynomolgus monkeys. In summary, SKG1201, a new generation vector which exemplifies a synergistic effect of liver de-targeting and restoration of high expression in the spinal cord, is a prospective gene therapy product for IT delivery to type II/III SMA patients."

Gene therapy • Gene Therapies • Genetic Disorders • Hepatology • Movement Disorders • Muscular Atrophy • Rare Diseases

STEER: Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P3 | N=125 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases

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 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

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

STEER: Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P3 | N=125 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases

STEER: Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P3 | N=125 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2024 ➔ Feb 2025 | Trial primary completion date: Jul 2024 ➔ Dec 2024

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

ADENO-ASSOCIATED VIRUS (AAV) GENE THERAPY FOR SPINAL MUSCULAR ATROPHY (WCN 2023) - P1, P3 | "Results of the STRONG study (NCT03381729) will be highlighted where children 6 to 60 months old received a single intrathecal (IT) dose of onasemnogene abeparvovec. AAV9-related side effects will be reviewed with a view to discussing vector, disease and patient-specific considerations when evaluating potential candidacy for gene replacement therapy."

Gene therapy • CNS Disorders • Muscular Atrophy

Intravenous and intrathecal onasemnogene abeparvovec gene therapy in symptomatic and presymptomatic spinal muscular atrophy (SMA): long-term follow-up study (WMS 2023) - No abstract available

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

Two years of newborn screening for spinal muscular atrophy in Poland (EPNS 2023) - "Objective: Spinal muscular atrophy (SMA) is a severe genetic condition, that can be successfully treated with targeted therapies (Nusinersen, Ridiplam, ZolgenSMA)... The PCR-HRM method was successfully used in NBS-SMA and our procedure allowed to quickly identify positive patients that can be treated with available therapies. The calculated prevalence of SMA is about 1/7300 in Polish population."

Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study (EPNS 2023) - P3 | "Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA."

Gene therapy • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pneumonia • Rare Diseases • Respiratory Diseases

Gene Therapy for Spinal Muscular Atrophy (SMA): A Review of Current Challenges and Safety Considerations for Onasemnogene Abeparvovec (Zolgensma). (PubMed, Cureus) - "Long-term benefits and risks have not been determined, but it is more cost-effective and requires less time of treatment compared to the other used drug, nusinersen. Therefore, the combined safety, cost, and effectiveness of onasemnogene abeparvovec make it a reliable treatment option for treating SMA Type 1."

Gene therapy • Journal • Review • Gene Therapies • Genetic Disorders • Hepatology • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases • SMA4

Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study (AAN 2023) - P3 | "Of those receiving add-on therapy, half did not achieve a new developmental milestone after initiation of add-on therapy. Conclusions Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA."

Gene therapy • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pneumonia • Rare Diseases • Respiratory Diseases