Risdiplam (2) – Evrysdi®

Spinal muscular atrophy, < 2 months

Characteristics

Start date 15.09.2023 – Marketing authorisation: 16.08.2023
Resolution 07.03.2024
INN Risdiplam
Brand name Evrysdi®
Pharm. company Roche Pharma AG
G-BA Procedure ID D-974
ATC code M09AX10 Other drugs for disorders of the musculo-skeletal system (M09AX)
ICD-10 codes (AIS) G12.0Infantile spinal muscular atrophy, type I [Werdnig-Hoffman], G12.9Spinal muscular atrophy, unspecified
Alpha-ID codes (AIS) I3473Infantile spinal muscular atrophy type I, I90303Spinal muscular atrophy
Therapeutic area Nervous system diseases Spinal muscular atrophy (SMA)
Reason for procedure New therapeutic indication

Therapeutic indication of the resolution

Evrysdi is used to treat 5q-associated spinal muscular atrophy (SMA) in patients with clinically diagnosed type 1, type 2 or type 3 SMA or with one to four copies of the SMN2 gene.

Subpopulation Indication Comparator
a) Pre-symptomatic patients aged < 2 months with a 5q-associated SMA and with up to three copies of the SMN2 gene Therapy according to the doctor's instructions, taking into account Nusinersen and Onasemnogen-Abeparvovec
b) Symptomatic patients aged < 2 months with clinically diagnosed type 1 SMA Therapy according to the doctor's instructions, taking into account Nusinersen and Onasemnogen-Abeparvovec
c) Pre-symptomatic patients aged < 2 months with a 5q-associated SMA and four copies of the SMN2 gene Therapy according to the doctor's instructions, taking into account Nusinersen and Onasemnogen-Abeparvovec

Studies and Results

No. of studies
(best subpopulation)
1 (RAINBOWFISH)
Study design
(best subpopulation)
Single-arm + no comparison
Meta analysis
(best subpopulation)
no

  • Clinical trials
    • The RAINBOWFISH trial is available for the benefit assessment. This is an ongoing single-arm study involving 26 presymptomatic patients with genetic evidence of 5q-associated SMA, who were no older than 6 weeks at the time of their first dose of risdiplam.

a) Presymptomatic patients aged < 2 months with 5q-associated SMA and with up to three copies of the SMN2 gene

  • For presymptomatic patients aged < 2 months with 5q-associated SMA and up to three copies of the SMN2 gene, additional benefit is not proven.
  • The single-arm RAINBOWFISH study submitted by the pharmaceutical manufacturer does not allow for a comparison with the appropriate comparator therapy.
  • There is a lack of suitable comparative data to assess the additional benefit of risdiplam compared with the appropriate comparator therapy. The additional benefit is therefore not proven.
  • Taking into account the available evidence on the medical benefit of risdiplam, the severity of the condition and the statements from medical societies regarding the current reality of care, risdiplam may represent a relevant treatment option for presymptomatic patients aged < 2 months with 5q-associated SMA and carrying up to three copies of the SMN2 gene.
  • mortality
    • For presymptomatic patients aged < 2 months with up to 3 copies of the SMN2 gene, results from the single-arm RAINBOWFISH trial are available for the endpoint categories of mortality, morbidity and side effects.
  • morbidity
    • Results from the single-arm RAINBOWFISH study are available for the endpoint categories of mortality, morbidity and side effects in presymptomatic patients aged < 2 months with up to 3 copies of the SMN2 gene.
  • Side effects
    • Results from the single-arm RAINBOWFISH study are available for the endpoint categories of mortality, morbidity and side effects in presymptomatic patients aged < 2 months with up to 3 copies of the SMN2 gene.

b) Symptomatic patients aged < 2 months with a clinically diagnosed type 1 SMA

  • For symptomatic patients aged < 2 months with clinically diagnosed type 1 SMA, additional benefit is not proven.
  • No data are available for symptomatic patients aged < 2 months with a clinically diagnosed type 1 SMA. An additional benefit is therefore not proven.
  • Taking into account the available evidence on the medical benefit of risdiplam, the severity of the condition and the statements from medical societies regarding the current reality of care, risdiplam may represent a relevant treatment option for symptomatic patients aged < 2 months with clinically diagnosed type 1 SMA.

c) Presymptomatic patients aged < 2 months with 5q-associated SMA and four copies of the SMN2 gene

  • For presymptomatic patients aged < 2 months with 5q-associated SMA and four copies of the SMN2 gene, additional benefit is not proven.
  • For presymptomatic patients aged < 2 months with four copies of the SMN2 gene, results are available from the single-arm RAINBOWFISH trial for the endpoint categories of mortality, morbidity and side effects. Five patients with ≥ 4 copies of the SMN2 gene were included in the study; it is therefore unclear what proportion of patients have exactly 4 copies of the SMN2 gene.
  • There is a lack of suitable comparative data to assess the additional benefit of risdiplam compared with the appropriate comparator therapy. The additional benefit is therefore not proven.
  • Taking into account the available evidence on the medical benefit of risdiplam, the severity of the condition and the statements from medical societies regarding the current reality of care, risdiplam may represent a relevant treatment option for presymptomatic patients aged < 2 months with 5q-associated SMA and four copies of the SMN2 gene.
  • mortality
    • For presymptomatic patients aged < 2 months with four copies of the SMN2 gene, results are available from the single-arm RAINBOWFISH study for the endpoint categories of mortality, morbidity and side effects.
  • morbidity
    • Results from the single-arm RAINBOWFISH trial are available for the endpoint categories of mortality, morbidity and side effects in presymptomatic patients aged < 2 months with four copies of the SMN2 gene.
  • Side effects
    • For presymptomatic patients aged < 2 months with four copies of the SMN2 gene, results are available from the single-arm RAINBOWFISH trial for the endpoint categories of mortality, morbidity and side effects.

Courtesy translation only, please refer to the German original.

Associated procedures

Risdiplam (2) Evrysdi® Roche Pharma AG Nervous system diseases Spinal muscular atrophy, < 2 months 56–95 100% additional benefit not proven
Risdiplam (1) Evrysdi® Roche Pharma AG Nervous system diseases 5q-associated spinal muscular atrophy (SMA) 992–2,142 42% Hint for non-quantifiable additional benefit Orphan


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