Umeclidinium (1) – Incruse®

a) Adult patients with COPD of moderate severity or greater (50 % ≤ FEV1 < 80 % predicted)

• The additional benefit is not proven.
• Mortality – overall mortality
  • In the study, no deaths occurred in the relevant patient population in either the tiotropium arm or the umeclidinium arm.
  • This provides no hint of an additional benefit of umeclidinium compared with tiotropium for the endpoint ‘overall mortality’.
• Morbidity – COPD symptoms (TDI responders)
  • This endpoint was no longer assessed at the 24-week mark.
  • Consequently, the additional benefit of umeclidinium compared with tiotropium for the endpoint ‘TDI responders’ is not proven.
• Morbidity – COPD symptoms (CAT responders)
  • The COPD Assessment Test (CAT) measures COPD symptoms and the associated impairments in patients’ daily lives.
  • The ‘CAT responder’ endpoint refers to patients with a reduction in their CAT score of ≥ 2 points.
  • In the umeclidinium arm, 51 per cent of patients showed an improvement in their condition, compared with approximately 41 per cent in the tiotropium arm.
  • These results do not differ statistically significantly (RR 1.25 [0.77; 2.03]; p = 0.528) and an additional benefit of umeclidinium compared with tiotropium is not proven for the ‘CAT responder’ endpoint.
• Morbidity – exacerbations
  • No analyses were available for the endpoint ‘exacerbations (moderate and severe)’ at the time of the dossier submission.
  • In its written statement, the pharmaceutical manufacturer states that an exacerbation occurred in approximately 21 % of patients in the umeclidinium arm and in approximately 15 % of patients in the tiotropium arm.
  • These results do not differ to a statistically significant extent.
  • An additional benefit of umeclidinium compared with tiotropium for the endpoint ‘exacerbations’ is not proven.
• Morbidity – Severe exacerbations
  • In the 2013 study¹⁶, severe exacerbations occurred in 2 patients in the umeclidinium arm and in no patients in the tiotropium arm.
  • No statistically significant difference was observed between the treatment groups (RR 5.00 [0.25; 100.89]; p = 0.208).
  • Consequently, additional benefit is not proven from umeclidinium compared with tiotropium for the endpoint ‘severe exacerbations’.
• Health-related quality of life – SGRQ responders
  • The endpoint ‘SGRQ responder’ refers to patients who show a reduction in their SGRQ score of at least 4 points.
  • In the umeclidinium arm, approximately 38% of patients showed an improvement in quality of life, compared with approximately 49% in the tiotropium arm.
  • However, these results do not differ to a statistically significant extent (RR 0.79 [0.47; 1.32]; p = 0.528).
  • An additional benefit of umeclidinium compared with tiotropium is therefore not proven for the ‘SGRQ responder’ endpoint.
• Side effects – severe adverse events (SAEs) and discontinuation due to adverse events (AEs)
  • For the endpoints ‘severe adverse events (SAEs)’ and ‘discontinuation due to adverse events (AEs)’, no statistically significant difference was observed between the treatment groups.
  • An additional benefit of umeclidinium compared with tiotropium is not proven for either endpoint.
• Conclusion
  • Overall, no advantages of umeclidinium were observed with regard to patient-relevant endpoints in the patient population a) “adult patients with COPD of moderate severity or greater (50% ≤ FEV1 < 80% predicted)”.
  • An additional benefit of umeclidinium over tiotropium is not proven in this patient population.

b) In patients with more severe disease (30% ≤ FEV1 < 50% of predicted or FEV1 < 30% of predicted, or respiratory failure) with ≥ 2 exacerbations per year

• The additional benefit is not proven.
• As this patient population comprises only one patient, the pharmaceutical manufacturer has not provided any data in the dossier.
• Consequently, an additional benefit of umeclidinium compared with tiotropium for “patients with more severe disease (30% ≤ FEV1 < 50% of predicted or There is no proof that FEV1 < 30% of predicted or respiratory failure) with ≥ 2 exacerbations per year’ is true.

Courtesy translation only, please refer to the German original.