Novartis AG — Zolgensma EMA EPAR public assessment report (EMEA/H/C/004750, 2020)
Novartis AG · 2020 · EMA EPAR public assessment report · company profile →
Report summary
The EMA granted Zolgensma (onasemnogene abeparvovec) a Conditional Marketing Authorisation in March 2020 for Spinal Muscular Atrophy (SMA) Type 1, recognizing its potential to address a significant unmet medical need. The regulatory assessment, initially accelerated, reverted to standard due to data deficiencies. Quality aspects, including manufacturing processes (Process A and B), characterization, and stability, were thoroughly reviewed. Non-clinical studies in various animal models highlighted the importance of early administration for efficacy, but also revealed cardiovascular and liver toxicity, particularly with Process B material, and dorsal root ganglia toxicity in non-human primates. Clinical trials (CL-101, CL-303, etc.) demonstrated significant improvements in survival, motor milestones, and CHOP-INTEND scores compared to natural history, especially in younger patients. Common adverse events included elevated liver enzymes and pyrexia, with rare but serious cardiac events and acute liver failure. The limited safety database necessitates ongoing monitoring for long-term safety and efficacy, particularly regarding potential cardiac and DRG toxicities.
Key findings — cited to the page
| Patients with Grade 5 TEAE (fatal) | 2 % | Zolgensma · p.106 |
| Patients with at least 1 Grade 3 or higher TEAE (all studies, proposed therapeutic dose) | 40.2 % | Zolgensma · p.106 |
| Patients with at least one Grade 3 or higher TEAE | 40 % | Zolgensma · p.104 |
| DRG toxicity severity grades | 2-4 | · p.51 |
| Age of symptom onset for SMA Type 1 | <6 months | · p.12 |
| Life expectancy for SMA Type 1 with 2 copies of SMN2 | <2 years | · p.12 |
| Proportion of 5q SMA cases due to homozygous deletions | 95 % | · p.11 |
| Zolgensma AS concentration range | 3.4 to 7.3 x 10e13 vector genome-containing particles per millilitre | · p.14 |
| SMA Type 1 prevalence | 45-60 % | · p.12 |
| Zolgensma FP target concentration | 2.0 x 1013 vg/mL | · p.18 |
| Shelf-life for Zolgensma FP at <-60°C | 12 months | Zolgensma FP · p.22 |
| Zolgensma active substance concentration | 2.0 x 10e13 vg/mL | · p.14 |
Source: Novartis AG ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Neurology library →