Benralizumab (2) – Fasenra®

• Clinical trials
  • The MANDARA trial comprises a double-blind, randomised controlled phase comparing benralizumab with mepolizumab in adults with EGPA over 52 weeks, followed by a single-arm, open-label extension phase with benralizumab for at least 1 year.

a) Adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) presenting with organ-threatening or life-threatening manifestations; for add-on treatment

• For the add-on treatment of adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) presenting with organ-threatening or life-threatening manifestations, the pharmaceutical manufacturer has not submitted any studies comparing the treatment with the appropriate comparator therapy.
• An additional benefit of benralizumab compared with the appropriate comparator therapy has therefore not been demonstrated for the add-on treatment of adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) with organ-threatening or life-threatening manifestations does not provide proof.

b) Adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis without organ-threatening or life-threatening manifestations; for add-on treatment

• Additional benefit is not proven for the add-on treatment of adults with relapsing or refractory EGPA without organ-threatening or life-threatening manifestations.
• mortality
  • No deaths occurred during the 52-week double-blind phase of the MANDARA trial.
• Morbidity – Remission
  • Remission was defined as the absence of any disease activity (BVAS = 0) and the achievement of a specific OCS dose threshold of either ≤ 7.5 mg/day, ≤ 4 mg/day or 0 mg/day (steroid-free remission).
  • For the endpoint of remission within the first 24 weeks up to week 52 with an OCS threshold of 7.5 mg/day, there was no statistically significant difference between the treatment groups.
  • The endpoint ‘steroid-free remission’ is not used in this resolution to assess the additional benefit, as there are fundamental uncertainties as to whether the time periods presented by the pharmaceutical manufacturer are appropriate for the endpoint ‘steroid-free remission’.
• Morbidity – Relapse
  • In the MANDARA study, the endpoint ‘relapse’ is defined as a worsening or persistence of active disease since the last visit.
  • No statistically significant differences were observed between benralizumab and mepolizumab for the endpoint ‘relapse’ (annual rate).
• Morbidity – Asthma symptoms (assessed using the ACQ-6)
  • For the endpoint ‘asthma symptoms’ (assessed using the ACQ-6), there was no statistically significant difference between the treatment groups.
• Morbidity – Sinonasal symptoms (assessed using the SNOT-22)
  • No statistically significant difference was observed between the treatment groups for the endpoint of sinonasal symptoms.
• Morbidity – Impairment of daily activities (assessed using WPAI question 6)
  • No statistically significant difference was observed between the treatment groups for the endpoint ‘impairment of activity’.
• Morbidity – Symptoms (assessed using the PGIS)
  • No significant difference was observed between the treatment arms.
• Health-related quality of life (assessed using the SF-36v2)
  • For the endpoint ‘health-related quality of life’ (assessed using the SF-36v2), there was no statistically significant difference between the treatment groups for either the PCS or the MCS.
• Side effects
  • For the endpoints of serious adverse events (AEs) and discontinuation due to AEs, no statistically significant difference was observed between the treatment groups in either case.
• Overall assessment
  • In the morbidity category, there were neither advantages nor disadvantages for benralizumab compared with mepolizumab for the endpoints of remission, asthma symptoms (measured using the ACQ-6), sinonasal symptoms (measured using the SNOT-22), activity impairment (as measured by WPAI question 6), and symptoms (as measured by PGIS), there were neither advantages nor disadvantages for benralizumab compared with mepolizumab.
  • Similarly, in the category of health-related quality of life, as assessed using the generic SF-36 questionnaire, and in the category of side effects, there are no statistically significant differences between benralizumab and mepolizumab.
  • Overall, there are neither advantages nor disadvantages of benralizumab compared with the appropriate comparator therapy, mepolizumab. Additional benefit is not proven for the add-on treatment of adults with relapsing or refractory EGPA without organ-threatening or life-threatening manifestations.

Courtesy translation only, please refer to the German original.