Ublituximab (1) – Briumvi®

• Clinical trials
  • The pharmaceutical manufacturer has submitted data for the benefit assessment from the double-blind, randomised Phase III trials ULTIMATE I and II, in which ublituximab was compared with teriflunomide.

a) Adults with relapsing-remitting multiple sclerosis (RRMS) who have not yet received disease-modifying therapy and do not have any indications for a severe disease course

• Consequently, the G-BA concludes that ublituximab offers a minor additional benefit over teriflunomide in adults with relapsing-remitting multiple sclerosis who have not yet received disease-modifying therapy and do not have any indications for a severe disease course.
• Overall, the certainty of the evidence is classified as ‘indication’.
• mortality
  • The findings on overall mortality are based on the analyses of the safety data. In total, one fatal adverse event (AE) occurred among patients treated with ublituximab in the ULTIMATE I study.
• Morbidity – Confirmed relapses
  • For the endpoint of confirmed relapses, operationalised as the annual relapse rate, the meta-analysis shows a statistically significant difference in favour of ublituximab.
  • There is an effect modification by the characteristic of sex. Whilst no statistically significant difference between the treatment groups could be demonstrated for women, a statistically significant advantage of ublituximab was observed for men.
• Morbidity – Confirmed disability progression (EDSS-based)
  • For the endpoint of confirmed disability progression, no statistically significant difference was observed between the treatment groups.
• Morbidity – Severity of disability (Multiple Sclerosis Functional Composite [MSFC])
  • The meta-analysis showed no statistically significant difference between the treatment groups for the MSFC z-score.
• Morbidity – Fatigue (Fatigue Impact Scale [FIS])
  • In the meta-analysis of the total FIS score, no statistically significant difference was observed between the treatment groups in either case.
• Quality of life – Multiple Sclerosis Quality of Life 54 [MSQoL-54]
  • In the meta-analysis of the PHCS total score, a statistically significant difference in favour of ublituximab was observed for both improvement and deterioration.
  • However, no statistically significant differences between the treatment groups were found in the analyses of improvement and deterioration in the MHCS total score.
• Side effects – Serious adverse events (SUEs)
  • The meta-analytical assessments of SUEs show no statistically significant differences between the treatment groups. There is an effect modification by the characteristic of sex. Whilst a statistically significant difference in favour of ublituximab can be inferred for women, no statistically significant differences between the treatment groups were observed for men.
• Side effects – severe adverse events and therapy discontinuations due to adverse events
  • For the endpoints of severe AEs and therapy discontinuations due to AEs, the meta-analysis shows no statistically significant differences between the treatment groups in either case.
• Side effects – Specific side effects (infusion-related reactions, low lymphocyte count)
  • For the endpoints infusion-related reactions (adverse events) and low lymphocyte count (severe adverse events), the meta-analysis revealed statistically significant differences between the treatment groups in each case, to the disadvantage of ublituximab.
• Side effects – Infections and parasitic diseases (SUEs)
  • For the endpoint ‘infections and parasitic diseases’ (SUEs), the meta-analysis showed no statistically significant difference between the treatment groups.
• Side effects – alopecia (AEs)
  • For the endpoint alopecia (UEs), the meta-analysis revealed a statistically significant difference between the treatment groups in favour of ublituximab.
• Overall assessment
  • Overall, there are therefore advantages for the endpoint of confirmed relapses in the morbidity category and for the physical total score of the MSQoL-54 in the quality of life category. However, the observed advantages do not reflect other patient-relevant endpoints such as disability progression or fatigue and are therefore assessed in their minor extent.
  • Of particular note in the present patient population is the observed effect modification for the characteristic of sex. Thus, the statistically significant advantage demonstrated for the endpoint of confirmed relapses was confirmed in a subgroup analysis only for men, but not for women. This effect modification is also evident in the category of side effects at the endpoint of serious adverse events: here, there is no statistically significant difference for men, whilst a statistically significant disadvantage is observed for women.

b) Adults with relapsing-remitting multiple sclerosis (RRMS) who have not yet received disease-modifying therapy and who have indications for a severe disease course, as well as adults who exhibit an active disease course despite treatment with disease-modifying therapy

• The additional benefit is not proven.
• For adults with relapsing-remitting multiple sclerosis (RRMS) who have not yet received disease-modifying therapy and have indications for a severe disease course, as well as adults who demonstrate an active disease course despite treatment with disease-modifying therapy, no suitable studies could be identified to compare ublituximab with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.