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Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naive or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.

ABSTRACT: OBJECTIVES:In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agal?; 0.2 mg/kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall fractional shortening (MFS). RESULTS:Enrolled patients included 71 switch (median [range] age, 46.6 [5-84] years; male to female [M:F], 40:31) and 29 treatment naïve (38.7 [12-74] years; M:F, 14:15). Adverse events (AEs) were consistent with the known safety profile of agal?. Two switch patients had hospitalization due to possibly/probably drug-related serious AEs (one with transient ischemic attack, one with infusion-related AEs). One switch and two treatment-naïve patients discontinued treatment because of AEs. Three patients (one each switch, treatment naïve, and previous agal?) died; no deaths were considered drug-related. There was no significant change from baseline in LVMI or MFS in either group. Similarly, eGFR remained stable; mean?±?standard error annualized change in eGFR (mL/min/1.73 m(2)) was -2.40?±?1.04 in switch and -1.68?±?2.21 in treatment-naïve patients. CONCLUSIONS:This is the largest cohort of patients with Fabry disease who were started on or switched to agal? in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agal?, there were limitations, including not having stringent selection criteria and the lack of a placebo group.

SUBMITTER: Goker-Alpan O

PROVIDER: S-EPMC4484907 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.

Goker-Alpan Ozlem O Nedd Khan K Shankar Suma P SP Lien Yeong-Hau H YH Weinreb Neal N Wijatyk Anna A Chang Peter P Martin Rick R

JIMD reports 20150331

<h4>Objectives</h4>In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agalα; 0.2 mg/kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall ...[more]

PMID: 25822820

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Project description:AimsLong-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes.Methods and resultsSelf-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9-1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = -0.41 [-0.68, -0.15] mm/year, Ppre-post difference <0.01; IVST: n = 38, slope difference = -0.32 [-0.67, 0.02] mm/year, Ppre-post difference = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m2 /year, Ppre-post difference = 0.80).ConclusionsCardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function.

Dataset Information

Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naive or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.

Publications

Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.

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