Appraisal of onasemnogene abeparvovec and recommendations from different health authorities
| Country | Canada | France | Germany | The Netherlands | England |
| Authority | CADTH Canadian Drug Expert Committee (CDEC) (published on 26 March 2021) | Haute Autorité de Santé (HAS) [French National Authority for Health] (published on 16 December 2020) | Gemeinsamer Bundesausschuss (G-BA) [Federal Joint Committee] (published on 20 January 2022) | Zorginstituut Nederland (ZIN) [The National Health Care Institute] (published on 4 April 2021) | National Institute for Health and Care Excellence (NICE) (published on 7 July 2021) |
| Indication | Treatment of paediatric patients with 5q spinal muscular atrophy (SMA) with biallelic mutations in the survival motor neuron 1 (SMN1) gene and three or fewer copies of SMN2 gene, or infantile-onset SMA. | Patients with 5q SMA with a biallelic mutation of the SMN1 gene and having a clinical diagnosis of SMA type 1, or patients with 5q SMA with a biallelic mutation of the gene SMN1 and up to three copies of the SMN2 gene. | Patients with 5q-associated SMA with a biallelic mutation in SMN1 gene and one clinically diagnosed SMA type 1, or up to three copies of the SMN2 gene. | Patients with SMA:
| Expected to be indicated for the single treatment of 5q13 SMA type 1. |
| Paediatric population | Health Canada (≥8 months of age): the efficacy and safety of onasemnogene abeparvovec in paediatric patients 8 months of age and older at the time of infusion have not been established in clinical trials. | EMA: there is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. | EMA: there is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. | EMA: there is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. | MHRA: there is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. |
| Recommendation | Conditional recommendation to be reimbursed for the treatment of paediatric patients with 5q SMA with biallelic mutations in the SMN1 gene. Conditioned to initiation criteria, prescribing conditions and price reduction. | Reimbursement for the treatment of patients with 5q SMA (biallelic mutation of the SMN1 gene), with a clinical diagnosis of SMA type 1 and type 2 or presymptomatic, with up to three copies of the SMN2 gene. | No added benefit of onasemnogene abeparvovec has been proven for any type of SMA. | Cost-effectiveness is unfavourable and very uncertain. Conditional recommendation to be included in the insured package with price reduction, pay for performance and joint price negotiation with Belgium and Ireland. | Recommended to be offered at the NHS under managed access agreement, including additional data collection. |
| Limitations | Major limitations are the lack of a concurrent control group that precludes a precise estimation of the magnitude of benefit and lack of information on the long-term comparative clinical effectiveness of onasemnogene abeparvovec versus comparators. | Uncertainties of long-term effect and significant limitation related to the absence of a robust direct or indirect comparison with nusinersen, which does not make it possible to know exactly the place of onasemnogene abeparvovec in the therapeutic strategy of patients with SMA type 1. | No direct comparison studies were available. In addition, different exclusion criteria and study populations (age, severity of disease) in the different studies make comparisons difficult. No suitable data were available for three of the four research questions. | Uncertainties about the long-term effects and the use of additional treatments (such as nusinersen). | Small sample sizes in all clinical trials; naïve comparison of the indirect comparison with nusinersen does not preserve within-study randomisation or consider differences in study effects, all results should be interpreted with caution. |
| Recommended price reduction | More than 90%. | Recommend an agreement with additional data collection. | Collection of further evidence. | At least 50%, pay for performance. | Managed access agreement with further data collection. |
| Sources | CADTH: https://cadth.ca/sites/default/files/cdr/complete/SG0649 Zolgensma - CDEC Final Recommendation March 26%2C 2021 for posting.pdf (accessed on 20 January 2022) | HAS: https://www.has-sante.fr/upload/docs/application/pdf/2021-11/zolgensma_161220_summary_ct18743.pdf(accessed on 20 January 2022) | G-BA: https://www.g-ba.de/beschluesse/5246/ (accessed on 25 January 2022) | Zin: https://www.zorginstituutnederland.nl/over-ons/publicaties/adviezen/2021/04/23/acp-advies-over-onasemnogene-abeparvovec-zolgensma (accessed on 20 January 2022) | NICE: https://www.nice.org.uk/guidance/hst15/evidence/evaluation-consultation-committee-papers-pdf-9191287693 (accessed on 20 January 2022) |
CADTH, Canadian Agency for Drugs and Technologies in Health (Canada); EMA, European Medicines Agency (Europe); MHRA, Medicines and Health Products Regulatory Agency (UK); NHS, National Health Service; SMA, spinal muscular atrophy ; SMN, survival motor neuron.