Migalastat (3) – Galafold®

• Clinical trials
  • The ATTRACT study (AT1001-012) is an open-label RCT in which migalastat was compared with enzyme replacement therapy (ERT).

Adults and adolescents aged 12 years and over with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) who have a mutation responsive to treatment

• For adults and adolescents aged 12 years and over with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) who have a mutation responsive to treatment, additional benefit is not proven.
• mortality
  • No deaths occurred during the course of the study.
• Morbidity – Cardiac morbidity
  • The endpoint of cardiac morbidity was operationalised using the patient-relevant individual components of myocardial infarction, unstable angina pectoris, new symptomatic arrhythmia and heart failure.
  • No myocardial infarctions or unstable angina pectoris occurred during the study.
  • No statistically significant difference was observed between the treatment groups for the endpoint of cardiac morbidity.
• Morbidity – Cerebrovascular morbidity
  • The endpoint of cerebrovascular morbidity was operationalised using the patient-relevant individual components of stroke and transient ischaemic attack (TIA).
  • However, no strokes occurred in the study.
  • No statistically significant difference was observed between the treatment groups for the endpoint of cerebrovascular morbidity.
• Morbidity – Pain
  • In the ATTRACT study, the endpoint ‘pain’ was assessed using the Brief Pain Inventory – Short Form (BPI-SF).
  • For the endpoint of worst pain (BPI-SF), there was no statistically significant difference between the treatment arms.
• Health-related quality of life
  • Health-related quality of life was assessed in the ATTRACT study using the Short Form-36 Health Survey Version 2 (SF-36v2).
  • The responder analyses at the 18-month assessment point showed no statistically significant difference between the treatment arms for either the physical composite score (PCS) or the mental composite score (MCS) of the SF-36v2.
• Side effects – Serious adverse events (SUEs)
  • No statistically significant difference was observed between the treatment groups for the SUEs endpoint.
• Side effects – Withdrawal due to adverse events (AEs)
  • There were no discontinuations due to AEs during the course of the study.
• Side effects – Infusion-related reactions
  • Infusion-related reactions represent a relevant side effect for this benefit assessment, as the administration of agalsidase alfa and agalsidase beta frequently leads to infusion-related reactions, according to the summary of product characteristics (SmPC).
  • However, this endpoint was not assessed in the ATTRACT study.
  • The analyses submitted subsequently by the pharmaceutical manufacturer regarding the endpoint ‘reactions associated with infusion’ are therefore not suitable for the benefit assessment.
• Overall assessment
  • Results from the ATTRACT RCT were submitted to assess the additional benefit of migalastat compared with the appropriate comparator therapy, namely enzyme replacement therapy with agalsidase alfa or agalsidase beta.
  • No deaths occurred during the course of the study; consequently, no conclusions regarding additional benefit can be drawn for the mortality category.
  • In the morbidity category, the endpoints of cardiac morbidity, cerebrovascular morbidity and pain were taken into account. For each of these endpoints, no statistically significant difference was observed between the treatment groups. An additional benefit for migalastat is therefore not proven in the morbidity category.
  • In the health-related quality of life category, the responder analyses at the 18-month assessment point showed no statistically significant differences between the treatment groups. Consequently, no additional benefit can be inferred for the health-related quality of life category either.
  • In the category of side effects, additional benefit is also not proven due to the absence of statistically significant differences between the treatment groups.
  • In summary, an additional benefit of migalastat over the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.