Migalastat (2) – Galafold®

• Clinical trials
  • The AT1001-020 study is a completed, single-arm, open-label Phase IIIb trial in which 22 adolescents aged 12 to < 18 years and weighing ≥ 45 kg, diagnosed with Fabry disease and amenable (= migalastat-sensitive) GLA mutation were treated with migalastat.

Adolescents aged 12 to < 16 years with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) who have a mutation responsive to treatment

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Consequently, the G-BA classifies the extent of the additional benefit of migalastat for the treatment of adolescents aged 12 to < 16 years with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) who have a mutation responsive to treatment as non-quantifiable, due to the limited data available, in accordance with the criteria set out in Section 5(7) of the AM-NutzenV.
• An additional benefit exists in accordance with Section 35a(1), sentence 11, first half-sentence, of SGB V, but is non-quantifiable because the scientific evidence does not permit this.
• mortality
  • No deaths occurred in the AT1001-020 study.
  • No conclusion can be drawn regarding the extent of the additional benefit, as there is no control group.
• morbidity
  • At month 12 or upon premature withdrawal, 6 participants (50.0%) reported an improvement in the PGI-C for ‘diarrhoea’, ‘total pain’ and ‘activities of daily living’, whilst 5 participants (41.7 %) reported an improvement in the PGI-C for ‘abdominal pain’ compared with baseline.
  • A deterioration was reported by 1 person (8.3 %) each in the PGI-C for ‘abdominal pain’, ‘total pain’ and ‘activities of daily living’ at month 12 or upon early withdrawal.
  • The results of the a priori planned continuous analysis are used for the benefit assessment.
  • In summary, only in the ‘abdominal pain’ and ‘fatigue’ subscales of both age-specific versions of the FPHPQ was there a slight improvement in scores at month 6 compared with baseline.
• quality of life
  • In summary, the PedsQL total score and the two summary scales show a slight improvement in health-related quality of life by month 6 compared with the baseline value.
  • However, in the present evaluation, it is not possible to provide a valid interpretation and assessment of the results due to the lack of a control group.
• Side effects
  • Serious adverse events (SAEs) were observed in 1 out of 14 participants in the AT1001-020 study; severe adverse events (AEs, CTCAE grade ≥ 3) occurred in 2 out of 14 participants whilst on treatment with migalastat.
  • In the AT1001-020 study, no participant discontinued treatment with migalastat due to AEs.
  • AE of any severity that occurred in ≥ 10% of participants in the study were most frequently (approximately 64% of patients) observed in the system organ class ‘infections and parasitic diseases’.
  • An overall analysis of the results on side effects does not allow any conclusions to be drawn regarding the extent of the additional benefit, as there is no control group.
• Summary assessment of the endpoints for the evaluation of symptoms and health-related quality of life
  • Symptoms vary from patient to patient in those with Fabry disease, as it is a multisystem disorder in which different organs may be primarily affected.
  • In the present study, AT1001-020, disease-specific symptoms and patient-reported changes in symptoms, as well as health-related quality of life, were recorded in adolescent patients with Fabry disease, amongst other things.
  • Consequently, no conclusions regarding additional benefit can be drawn on the basis of these endpoints.
• Overall assessment / Conclusion
  • The benefit assessment of migalastat for the treatment of adolescents aged 12 to < 16 years with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) who have a mutation responsive to treatment was based on the single-arm, uncontrolled study AT1001-020.
  • Results are available from the AT1001-020 study on patient-relevant endpoints in the categories of mortality, morbidity, quality of life and side effects.
  • No deaths occurred in the AT1001-020 study. No conclusion can be drawn regarding the extent of the additional benefit, as there was no control group.
  • The study also assessed endpoints relating to disease-specific symptoms and patient-reported changes in symptoms. Health-related quality of life was assessed using a measurement tool suitable for the paediatric patient population. However, in the present assessment, it is not possible to make a valid interpretation and evaluation of the results due to the lack of a control group. Therefore, no conclusions can be drawn regarding the extent of the additional benefit in the categories of morbidity and quality of life.
  • In the ‘Side effects’ category, a comparative assessment is not possible on the basis of the results presented. No conclusions can be drawn regarding the extent of the additional benefit.
  • Overall, there is a hint of a non-quantifiable additional benefit, as the scientific data do not permit quantification.

Courtesy translation only, please refer to the German original.