Onasemnogen-Abeparvovec (2) – Zolgensma®

• Clinical trials
  • The ENDEAR trial is a double-blind RCT that enrolled patients with genetically confirmed 5q-associated SMA.
  • The CS3A trial is a single-arm dose-escalation study that enrolled a total of 21 patients with genetically confirmed 5q-associated SMA.
  • The SHINE study is an open-label, long-term study involving patients who had previously taken part in a study with nusinersen.

a) Patients with type 1 5q-associated spinal muscular atrophy (5q-SMA)

• The additional benefit is not proven.
• Taking into account the available evidence on the medical benefit of onasemnogen abeparvovec, the severity of the condition and the statements from medical societies regarding the current reality of care, onasemnogen abeparvovec may represent a relevant treatment option for patients with type 1 5q-SMA.
• For this patient population, the pharmaceutical manufacturer has not identified any randomised controlled trials (RCTs) that allow for a direct or an adjusted indirect comparison, via a common bridge comparator, with the appropriate comparator therapy, nusinersen.
• The pharmaceutical manufacturer therefore presents individual arms from various studies for a comparison between onasemnogen abeparvovec and nusinersen.
• However, there are marked differences in the mean duration of disease between the patient populations considered for onasemnogen-abeparvovec and nusinersen, which constitutes a very significant confounder.
• Furthermore, there are differences in the inclusion and exclusion criteria regarding ventilation and respiratory symptoms, meaning that patients with a potentially less favourable prognosis regarding respiratory events at the start of the study were included in the nusinersen trials.
• The recalculation of the indirect comparison submitted in the pharmaceutical manufacturer’s written statement for the patient population in the onasemnogen abeparvovec and nusinersen trials with a disease duration of ≤ 12 weeks also exhibits uncertainties.
• The comparisons presented of individual arms from different trials between onasemnogen abeparvovec and nusinersen are unsuitable for benefit assessment of onasemnogen-Abeparvovec and, accordingly, cannot be used to derive an additional benefit.

b) Patients with 5q-SMA type 2 and up to 3 copies of the SMN2 gene

• The additional benefit is not proven.
• Taking into account the available evidence on the medical benefit of onasemnogen-abeparvovec, the severity of the condition and the statements from medical societies regarding the current reality of care, onasemnogen-abeparvovec may represent a relevant treatment option for patients with 5q-SMA type 2 and up to 3 copies of the SMN2 gene.
• The pharmaceutical manufacturer has not provided any data for the assessment of the additional benefit of onasemnogen abeparvovec compared with nusinersen.

c) Patients with 5q-SMA type 3 and up to 3 copies of the SMN2 gene

• The additional benefit is not proven.
• Taking into account the available evidence on the medical benefit of onasemnogen abeparvovec, the severity of the condition and the statements from medical societies regarding the current reality of care, onasemnogen-abeparvovec may represent a relevant treatment option for patients with 5q-SMA type 3 and up to 3 copies of the SMN2 gene.
• The pharmaceutical manufacturer has not provided any data for the assessment of the additional benefit of onasemnogen-abeparvovec compared with treatment as clinically indicated, with a choice of nusinersen or best standard care (BSC).

d) Presymptomatic patients with 5q-SMA and up to 3 copies of the SMN2 gene

• The additional benefit is not proven.
• Taking into account the available evidence on the medical benefit of onasemnogen-abeparvovec, the severity of the condition and the statements from medical societies regarding the current reality of care, onasemnogen-abeparvovec may represent a relevant treatment option for presymptomatic patients with 5q-SMA and up to 3 copies of the SMN2 gene.
• The pharmaceutical manufacturer identifies, for the present question, the ongoing, single-arm SPR1NT study for onasemnogen-abeparvovec and the single-arm NURTURE study for nusinersen; however, it does not carry out a comparison of individual arms from the two studies.
• Consequently, no suitable data are available for assessing the additional benefit of onasemnogene abeparvovec compared with nusinersen.

Courtesy translation only, please refer to the German original.