MO068EFFICACY AND SAFETY OF MIGALASTAT, AN ORAL PHARMACOLOGICAL CHAPERONE FOR FABRY DISEASE: RENAL FINDINGS FROM TWO RANDOMIZED PHASE 3 STUDIES (FACETS AND ATTRACT)

INTRODUCTION AND AIMS: Fabry disease is an X-linked disorder of lysosomal α-galactosidase A (α-Gal A) deficiency, leading to substrate accumulation, multiorgan disease, and progressive decline in renal function. Accumulation of GL-3 in the kidney is a known consequence of Fabry disease. We examined whether administration of migalastat, an oral pharmacological chaperone that induces proper folding of specific mutant forms of α-Gal A and increases trafficking to lysosomes, helps stabilize renal function in patients with Fabry disease. METHODS: Two randomized phase 3 studies were conducted for migalastat 150 mg QOD. FACETS (011, NCT00985301) was a 24-month trial, including a 6-month double-blind, placebo-controlled period, in 67 enzyme replacement therapy (ERT)-naive patients. ATTRACT (012, NCT01218659) was an active-controlled, 18-month trial in 57 ERT-experienced patients with a 12-month open-label extension (OLE). Efficacy analyses focused on patients with amenable mutations (FACETS, n=50; ATTRACT, n=53). A post hoc analysis examined the eGFR annualized rate of change from baseline in the range of 60 to <90 or >90 mL/min/1.73 m2; the range of 30 to <60 mL/min/1.73 m2 was not included due to the low number of patients in this group. RESULTS: In FACETS, analyses revealed statistically significant reductions in kidney interstitial capillary GL-3 from months 0 to 6 (placebo-controlled; P=0.008) and months 6 to 12 (P=0.014). Over 24 months, the annualized rate of change in eGFRCKD-EPI ± SD with migalastat was −0.3±4.2 . The annualized rate of change ±SD for eGFR in the range of 60 to <90 mL/min/1.73 m2 (−0.8±4.16) was comparable to the rate in the range of ≥90 mL/min/1.73 m2 (0.2±4.11). During the 18-month controlled period of ATTRACT, the annualized means ± SD for eGFR for migalastat (−0.40±4.3) and ERT (−1.03±7.4) were comparable. The annualized rates of change in eGFR ± SD in the range of 60 to <90 mL/min/1.73 m2 for migalastat and ERT were −0.2±5.32 and −7.3±15.90, respectively; the annualized rates in the range of ≥90 mL/min/1.73 m2 were −2.0±2.15 and −2.1±5.30. Predefined renal events occurred in 24% and 33% of patients on migalastat and ERT, respectively. During the 12-month OLE, eGFR remained stable. CONCLUSIONS: In FACETS and ATTRACT, renal function remained stable with migalastat across patient subgroups. Migalastat has promise as a first-in-class oral chaperone for patients with Fabry disease with amenable mutations.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.