title: Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.
abstract: OBJECTIVE
  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 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 agalα. 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 agalα) 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 agalα in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agalα, there were limitations, including not having stringent selection criteria and the lack of a placebo group.
authors.affiliation: Lysosomal Disorders Unit, O&O ALPAN LLC, Fairfax, VA, USA, ogokeralpan@oandoalpan.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
authors.forename: Khan
authors.initials: K
authors.lastname: Nedd
authors.forename: Suma P
authors.initials: SP
authors.lastname: Shankar
authors.forename: Yeong-Hau H
authors.initials: YH
authors.lastname: Lien
authors.forename: Neal
authors.initials: N
authors.lastname: Weinreb
authors.forename: Anna
authors.initials: A
authors.lastname: Wijatyk
authors.forename: Peter
authors.initials: P
authors.lastname: Chang
authors.forename: Rick
authors.initials: R
authors.lastname: Martin
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