EVRYSDI (risdiplam) - Spinal muscular atrophy (SMA)

Opinions on drugs - Posted on May 21 2025

Reason for request

Reassessment at the request of the CT

Summary of opinion

Favourable opinion for reimbursement only in “the treatment of 5q spinal muscular atrophy (SMA) in patients with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies.”

Unfavourable opinion for reimbursement in the other situations covered by the MA indication (i.e. patients with a clinical diagnosis of SMA Type 4).

Clinical Benefit

Substantial	The clinical benefit provided by EVRYSDI 0.75 mg/ml (risdiplam) powder for oral solution is substantial only in “the treatment of 5q spinal muscular atrophy (SMA) in patients with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies”.
Insufficient	The clinical benefit provided by EVRYSDI 0.75 mg/ml (risdiplam) powder for oral solution is insufficient to justify public funding in the other MA situations (i.e. patients with a clinical diagnosis of SMA Type 4).

Clinical Added Value

moderate

Considering:

the suggested efficacy of risdiplam in the RAINBOWFISH single-arm, phase 2 study, conducted in 26 pre-symptomatic patients with 2 copies (n=8), 3 copies (n=13) or 4 or more copies (n=5) of the SMN2 gene, aged from 1 day to 6 weeks at inclusion, in which, after 52 weeks of treatment, 4 out of 5 patients were able to sit without support for at least 5 seconds, the primary endpoint for this study assessed only in a subgroup of 5 patients with 2 SMN2 copies, and a CMAP (compound muscle action potential) amplitude of 1.5 mV; with this limiting approach on a very small number of patients and an endpoint less relevant than measurement over 30 seconds being debatable to assess the effect size of risdiplam,
the suggested efficacy of risdiplam, given the non-comparative nature of the study, on the exploratory secondary endpoints, this time assessed on the basis of the 26 patients enrolled, with, in particular, the proportion of patients capable of sitting without support for at least 30 seconds or change in HINE-2 score,
purely exploratory quality of life results that cannot be interpreted in the RAINBOWFISH study,
the safety profile of risdiplam, which appears to be favourable in the paediatric population, with follow-up limited to 1 year, however, in the RAINBOWFISH study,
uncertainties concerning the medium and long-term efficacy and safety of risdiplam in pre-symptomatic patients, given follow-up limited to 1 year in the RAINBOWFISH study,
the significant methodological limitations of the indirect comparison, meaning that it is not possible to rank the medicinal products available for pre-symptomatic patients,
the currently unmet medical need in pre-symptomatic patients with 4 SMN2 copies,

the Transparency Committee deems that EVRYSDI (risdiplam) provides a minor clinical added value (CAV IV) in the care pathway for pre-symptomatic patients with 1 to 4 copies of the SMN2 gene.

minor

Considering:

exploratory results after 5 years in the extension phase of the FIREFISH non-comparative study in symptomatic patients with type 1 SMA, which appear to confirm those initially assessed by the Committee with, in particular, the proportion of patients capable of sitting without support for at least 5 seconds,
exploratory results after 5 years in the open-label extension phase of the SUNFISH randomised, placebo-controlled study conducted in a heterogeneous population of symptomatic patients with SMA type 2 or 3, aged from 2 to 25 years at inclusion, which appear to confirm those initially assessed by the Committee with, in particular, the change in the MFM32 score,
the results of the EPICEAS observational study based on data collected in patients included in the SMA France registry, conducted at the request of the Committee, which suggest stabilisation of the disease, assessed using motor development scales (MFM32, RULM and HFMSE),
the absence of data on the cognitive development and quality of life of patients, for which no assessment was scheduled in the clinical studies,
the safety profile of risdiplam, which appears to be favourable, with longer follow-up,

the Transparency Committee considers that EVRYSDI (risdiplam) provides a moderate clinical added value (CAV III) in the same way as SPINRAZA (nusinersen) and ZOLGENSMA (onasemnogene abeparvovec), in the care pathway for symptomatic patients with SMA type 1, type 2 or type 3.