Satralizumab (1) – Enspryng®

• Clinical trials
  • SAkuraStar is a randomised, double-blind Phase III trial followed by an open-label extension period to investigate the efficacy and safety of satralizumab as monotherapy compared with placebo in the treatment of adults with NMOSD.
  • SAkuraSky is a randomised, double-blind Phase IIItrial followed by an open-label extension period to investigate the efficacy and safety of satralizumab in combination with a standard immunosuppressive therapy compared with placebo plus a standard immunosuppressive therapy in the treatment of adults and adolescents aged 12 years and over with NMOSD.

Adults and adolescents aged 12 years and over with neuromyelitis optica spectrum disorders (NMOSD) who are anti-aquaporin-4-IgG (AQP4-IgG) seropositive

• Overall, there is a hint of a minor additional benefit.
• In its overall assessment of the available results on patient-relevant endpoints, the G-BA classifies the extent of the additional benefit of satralizumab for the treatment of adults and adolescents aged 12 years and over with NMOSD, who are AQP4-IgG-seropositive, minor, based on the criteria set out in Section 5(8), sentences 1 and 2, in conjunction with Section 5(7), sentence 1, number 4 of the AM-NutzenV.
• mortality
  • No deaths were observed in the studies.
• Morbidity – disease relapses
  • The primary endpoint of both studies was the ‘time to first protocol-defined relapse’ during the double-blind study period.
  • In both studies, a statistically significant and clinically relevant advantage of satralizumab compared with placebo was observed for the relevant subpopulation in terms of time to the occurrence of a protocol-defined relapse.
  • Although the robustness of the effect observed in the primary analyses could not be fully supported by the sensitivity analyses, the pre-specified primary analysis – with strictly defined criteria for a standardised and as objective as possible assessment of a relapse – represents the methodologically more valid evaluation.
• Morbidity – disability progression (EDSS-based)
  • In the SAkuraStar study, satralizumab monotherapy showed a statistically significant advantage over placebo in terms of time to EDSS progression.
  • In the SAkuraSky study, treatment with satralizumab in combination with standard immunosuppressive therapy did not result in any statistically significant difference compared with placebo plus standard immunosuppressive therapy.
• Morbidity – visual acuity (Snellen test)
  • For both studies, due to the high proportion of missing values from week 48 onwards, only descriptive data for baseline and week 24 could be considered; these data do not allow any conclusions to be drawn regarding the effects of satralizumab on visual acuity.
• Quality of life – SF-36
  • Quality of life was not assessed in the available analyses following the onset of a relapse.
  • Accordingly, in both studies, the proportion of participants included in the analysis relative to the ITT population was already < 70 % in at least one of the two study arms at the first assessment point after baseline (week 24).
  • The SF-36 results are therefore considered invalid for the ITT population.
  • The effect of satralizumab on quality of life cannot therefore be assessed.
• Side effects
  • For the relevant patient population, no statistically significant differences were observed between the treatment arms in either study in the analysis of serious adverse events (SAEs).
  • For severe AEs, there was no statistically significant difference between the study arms in the SAkuraStar study; in the SAkuraSky study, no effect estimate could be calculated due to the low number of events.
  • Similarly, for AEs leading to discontinuation of the study medication, no effect estimate could be calculated due to the minor number of events.
• Overall assessment
  • Results from the two randomised, double-blind, placebo-controlled Phase III trials, SAkuraStar and SAkuraSky, are available for the benefit assessment of satralizumab in the treatment of adults and adolescents aged 12 years and over with NMOSD, who are AQP4-IgG-seropositive, results are available from the two randomised, double-blind, placebo-controlled Phase III trials, SAkuraStar and SAkuraSky.
  • No deaths occurred in either study.
  • In the morbidity category, both studies showed a statistically significant advantage in favour of satralizumab over placebo for the endpoint of disease relapses in the time to the occurrence of a protocol-defined relapse.
  • Given the methodologically sounder validity of protocol-defined relapses, the additional sensitivity analyses carried out do not call into question the positive effect of satralizumab on reducing relapses.
  • For the endpoint of disability progression (EDSS-based), a statistically significant advantage was also observed in the SAkuraStar study in favour of satralizumab as monotherapy compared with placebo in terms of the time to EDSS progression, whereas in the SAkuraSky study, no statistically significant difference was observed between the treatment arms.
  • For the visual acuity endpoint, only descriptive data are available.
  • No evaluable data are available for other patient-relevant endpoints in this indication, such as fatigue and pain.
  • Overall, the advantages in the endpoints of disease relapses and disability progression are assessed as having a minor extent.
  • No evaluable data are available in the quality of life category.
  • In the category of side effects, there are no statistically significant differences for serious AEs in either study, nor for severe AEs in the SAkuraStar study.
• Statistical significance of the evidence
  • On balance, the uncertainties mentioned regarding the strength of the evidence provide a hint of additional benefit.

Courtesy translation only, please refer to the German original.