Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry

Abstract

Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m² (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m² (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was -0.9 (-10.8, 9.9) mL/min/1.73 m²/year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient-years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real-world Fabry population.

Keywords: Fabry disease; migalastat; real world evidence.

FIGURE 1

Study design. eGFR, estimated glomerular filtration rate; ERT, enzyme replacement therapy.

FIGURE 2

LVMi by age at enrolment separated by males and females. The reference values for LVMi were based on the M mode linear method to avoid over attribution to LVH. Reference values for the 2D method are: females, 88 g/m² and males, 102 g/m². LVH, left ventricular hypertrophy; LVMi, left ventricular mass index; ULN, upper limit of normal.

FIGURE 3

Multiorgan involvement by sex. Each ring represents one patient with involvement of ≥2 organ systems. Each colour represents the involvement of an organ: the darker the shade, the more organ systems were involved (up to five) for that patient. (A) There are 48 rings, each representing one male patient with involvement of ≥2 organ systems. (B) There are 28 rings, each representing one female patient with involvement of ≥2 organ systems. The proportion of patients with involvement of each organ system is shown only for patients with involvement of ≥2 organ systems and is not indicative of the proportion of patients with organ involvement for the overall population. CNS, central nervous system; GI, gastrointestinal; PNS, peripheral nervous system.

FIGURE 4

Annualised rate of change in eGFR_CKD‐EPI by patient for (A) the overall patient population and (B) by sex. Solid magenta line indicates the mean eGFR_CKD‐EPI annualised rate of change. Annualised rate of eGFR change was calculated using three or more data points for 91/116 patients and two data points for 25/116 patients. The mean (95% CI) for (A) the overall patient population was −0.9 (−10.8, 9.9) mL/min/1.73 m²/year and (B) for males were −0.9 (−9.8, 13.3) mL/min/1.73 m²/year and for females were −0.9 (−11.0, 9.9) mL/min/1.73 m²/year. One female patient with an eGFR value ≥20 to <30 at enrolment met the inclusion criteria and was included in the study; however, treatment of this patient is considered off‐label. CI, confidence interval; CKD‐EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate.

FIGURE 5

Annualised rate of change in eGFR_CKD‐EPI for each patient by eGFR category at enrolment. Dark solid lines indicate the mean eGFR_CKD‐EPI annualised rate of change. Annualised rate of eGFR_CKD‐EPI change was calculated using three or more data points for 91/116 patients and two data points for 25/116 patients. The 95% CI for eGFR group ≥90 mL/min/1.73 m² at enrolment was −5.9, 8.3 mL/min/1.73 m²/year, for eGFR group ≥60 to <90 mL/min/1.73 m² at enrolment was −10.8, 11.3 mL/min/1.73 m²/year, and for eGFR group ≥30 to <60 mL/min/1.73 m² at enrolment was −7.5, 4.6 mL/min/1.73 m²/year. CI, confidence interval; CKD‐EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate.

FIGURE 6

Incidence of FACEs per 1000 patient‐years in patients who received migalastat. *Includes one death due to a cardiac event. FACE, Fabry‐associated clinical event.