Pegunigalsidase alfa (1) – Elfabrio®

• Clinical trials
  • The BALANCE trial is a randomised, double-blind, controlled Phase III trial in which treatment with pegunigalsidase alfa was compared with treatment with agalsidase beta.

Adults with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency)

• For adults with a confirmed diagnosis of Fabry disease (α-galactosidase deficiency), additional benefit is not proven.
• mortality
  • No deaths occurred during the course of the study.
• morbidity
  • Change in renal function (eGFR slope)
  • A change in renal function, as measured by the glomerular filtration rate, is not in itself clinically relevant to patients. Given the high median baseline eGFR values of 73.45 ml/min/1.73 m² in the intervention arm and 74.85 ml/min/1.73 m² in the control arm, and the minor change in renal function measured in the study (median change per year of approximately −2.5 and −2.2 ml/min/1.73 m² respectively), it cannot be assumed that the endpoint reflects a noticeable deterioration in renal function for the majority of the patients concerned. The endpoint ‘change in renal function’ (eGFR slope) is therefore not used for the benefit assessment in this analysis.
  • Combined endpoint for clinical morbidity in Fabry disease
  • Symptoms assessed using the Mainz Severity Score Index (MSSI)
  • Due to the uncertainties described, the results for the ‘symptoms’ endpoint, assessed using the MSSI, are not used for the benefit assessment.
  • Pain
  • Health status (EQ-5D Visual Analogue Scale)
  • For the health status endpoint, assessed using the EQ-5D VAS, there is no statistically significant difference between the treatment groups.
• quality of life
  • No data on health-related quality of life are available.
• Side effects
  • For the endpoints SUEs, severe AEs (CTCAE grade ≥ 3) and discontinuation due to AEs, there were no statistically significant differences between the treatment groups in any case.
  • Infusion-related reactions
  • Chest pain (SUEs), disorders of the respiratory tract, thoracic cavity and mediastinum (severe AEs)
  • For the endpoints chest pain (SUEs) and disorders of the respiratory tract, thoracic cavity and mediastinum (severe AEs), a statistically significant advantage was observed between the treatment groups in favour of pegunigalsidase alfa. However, due to the minor number of events (2 events for the endpoint ‘chest pain’ and 3 events for the endpoint ‘respiratory, thoracic and mediastinal disorders’) and the existing uncertainties in the BALANCE study, these effects are not, however, considered sufficient to conclude that pegunigalsidase alfa offers an additional benefit compared with agalsidase beta.
• Overall assessment
  • To assess the additional benefit of pegunigalsidase alfa compared with the appropriate comparator therapy, results from the BALANCE RCT (comparison with treatment using agalsidase beta) were presented for the endpoint categories of mortality, morbidity and side effects. 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 pain and health status were assessed using the visual analogue scale of the EQ-5D. For each of these endpoints, no statistically significant difference was observed between the treatment groups. An additional benefit for pegunigalsidase alfa is therefore not proven in the morbidity category. No data were presented for the health-related quality of life category; consequently, no additional benefit can be inferred. No additional benefit can be inferred in the ‘side effects’ category either. In summary, an additional benefit of pegunigalsidase alfa compared with the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.