Ozanimod (1) – Zeposia®

• Clinical trials
  • The RADIANCE B and SUNBEAM trials are randomised, double-blind, active-controlled, parallel-group trials, each comparing ozanimod with interferon beta-1a in patients with RRMS.

a) Adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease who have not yet received disease-modifying therapy, or adult patients previously treated with disease-modifying therapy whose disease is not highly active.

• Overall, there is an indication of a minor additional benefit of ozanimod compared with interferon beta-1a.
• Due to existing uncertainties regarding the representativeness of the study population in the German healthcare context, as well as the analysis of the data at month 12, an indication is derived for the certainty of the findings.
• mortality
  • No events were observed for the endpoint of all-cause mortality.
• Morbidity – Confirmed relapses (EDSS-based)
  • For the endpoint of confirmed relapses, the meta-analysis of annual relapse rates shows a statistically significant advantage for ozanimod compared with interferon beta-1a.
• Morbidity – Confirmed disability progression (EDSS-based)
  • For the endpoint of confirmed disability progression at 6 months, the meta-analysis showed no statistically significant difference between the treatment groups.
• Morbidity – Severity of disability (assessed using the Multiple Sclerosis Functional Composite [MSFC] score)
  • For the endpoint of severity of disability, the meta-analysis showed no statistically significant difference between the treatment groups for the MSFC z-score.
• Morbidity – visual acuity (Low Contrast Letter Acuity [LCLA])
  • For the endpoint of visual acuity, the meta-analysis showed no statistically significant difference between the two treatment groups.
• Morbidity – Fatigue
  • No data are available for the endpoint ‘fatigue’, as this endpoint was not assessed in either study.
• Side effects – severe adverse events (SUEs)
  • For SUEs, the meta-analysis shows no statistically significant difference between the treatment groups.
• Side effects – Specific adverse events (AEs)
  • For the endpoints infections and parasitic diseases (SOC, AEs) and psychiatric disorders (SOC, AEs), the meta-analysis at month 12 showed no statistically significant difference between the treatment groups in either case.
  • For the endpoint ‘flu-like illness’ (PT, AEs), the meta-analysis at month 12 showed a statistically significant advantage for ozanimod.
  • For the endpoint bradycardia (PT, AEs), the pharmaceutical manufacturer has not provided any data, as the number of events for this endpoint did not meet the frequency criteria for reporting.
• Side effects – discontinuation due to AEs
  • For the endpoint ‘discontinuation due to adverse events’, the meta-analysis shows no statistically significant difference between the treatment groups.
• Overall assessment
  • In the morbidity endpoint category, the meta-analysis of annual relapse rates shows a statistically significant advantage in favour of ozanimod compared with interferon beta-1a for the endpoint of confirmed relapses.
  • However, for the endpoints of confirmed disability progression (EDSS-based) at 6 months, severity of disability and visual acuity, no statistically significant difference was observed between the treatment groups. The endpoint of fatigue was not assessed in either study.
  • In the endpoint category of health-related quality of life, the disease-specific quality of life questionnaire (MSQoL) revealed no statistically significant or clinically relevant difference between the two treatment arms.
  • In the endpoint category of side effects, the meta-analysis revealed no statistically significant difference between the treatment groups, either in terms of serious side effects (SAEs) or discontinuations due to side effects. With regard to specific adverse events, however, the endpoint ‘flu-like illness’ showed that ozanimod caused minor harm compared with interferon beta-1a.
  • Overall, therefore, the extent of the positive effect of ozanimod compared with interferon beta-1a is minor for the endpoint of confirmed relapses. However, the observed advantage in reducing the relapse rate does not allow conclusions to be drawn regarding a possible effect on one of the endpoints of confirmed disability progression, which can generally only be assessed after a longer follow-up period.
  • The effects of ozanimod are therefore assessed as a moderate – rather than merely minor – improvement in treatment-related benefit compared with the appropriate comparator therapy, and the extent of the additional benefit is classified as minor.
  • Overall, therefore, a minor additional benefit of ozanimod compared with treatment with interferon beta-1a in patients with RRMS who have not yet received disease-modifying therapy for RRMS, and in those who have been previously treated with disease-modifying therapy but whose disease is not highly active.

b) Adult patients with relapsing-remitting multiple sclerosis (RRMS) with highly active disease despite treatment with a disease-modifying therapy.

• The additional benefit is not proven.
• However, for patients who still show high disease activity despite prior treatment, the appropriate comparator therapy determined by the G-BA – namely escalation to a more active therapy (alemtuzumab, fingolimod or natalizumab) – has not been implemented. Consequently, there are no suitable data available for these patients in comparison with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.