Fabrazyme was evaluated for reduction in clinically significant renal, cardiac, and cerebrovascular events
The rate of clinically significant events in Fabrazyme-treated patients vs. placebo-treated patients1
α-GAL A=α-galactosidase A; CI=confidence interval; EOW=every other week; HR=hazard ratio; IV=intravenous.
43% relative risk reduction of renal, cardiac, and cerebrovascular clinical events and death
In the unadjusted ITT population of Fabrazyme-treated patients vs. placebo2
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experienced clinical eventsa
A smaller percentage of people had heart, kidney, stroke events, or death.
(HR=0.57, 95% CI: 0.27, 1.22, p=0.14)
Adapted from Banikazemi M et al, 2007.1
aClinical event defined as renal, cardiac, or cerebrovascular event or death.2
ITT=intent-to-treat.
Study 2: A multicenter, randomized, double-blind, placebo-controlled study in which 82 patients (72 males and 10 females) were randomized 2:1 to receive either agalsidase beta (1 mg/kg, n=51) or placebo (n=31) EOW for up to 35 months. The study included patients aged 20 to 72 years (median age: 45), with a baseline median plasma α-GAL A level of 1.5 nmol/hour/mL (range: 0 to 1.5). The primary endpoint was time to first clinical event (renal, cardiac, or cerebrovascular event or death). Secondary analysis was performed for protocol-adherent patients with mild-to-moderate kidney dysfunction at baseline who were adjusted for baseline proteinuria.1
Think Fabrazyme first, think decreased incidence of severe clinical events over time3
Registry data: Incidence of combined severe clinical events in patients on ERT for up to 5 years3,a
Baseline characteristics3
- Many patients had advanced disease with a frequency of pre-ERT events of 17%, LVH 61%, and an eGFR <60 mL/min/1.73 m2 of 24%
- Patients who started Fabrazyme treatment at age ≥40 years had more evidence of renal and cardiac organ damage compared with patients who started treatment at age <40 years
- In patients who started ERT at age ≥40 years, the proportion of patients with eGFR <60 mL/min/1.73 m2 was 33%, compared with 15% of those who initiated ERT at age <40 years
- More patients who started treatment at age ≥40 years had a baseline urine protein:creatine ratio of >0.5 g/g (54% vs. 38%), LVH (79% vs. 37%), arrhythmias (30% vs. 17%), systolic blood pressure >130 mm Hg (47% vs. 35%), and diastolic blood pressure >80 mm Hg (46% vs. 30%) compared with those who started ERT at age <40 years
Adapted from Ortiz A et al, 2016.3
- After 6 months of Fabrazyme, the rate of severe clinical events decreased from 111 to 40-58 events per 1000 patient-years and remained stable for the remainder of the follow-up period3
- The largest decrease in incidence rates was among male patients and those aged ≥40 years when Fabrazyme was initiated3,b
- Among patients with pre-ERT clinical events, the risk of developing an event after starting Fabrazyme was not significantly different during 0-0.5 year compared with those who had no previous clinical events,c but increased thereafter3,d
- Retrospective, observational study analyzing the incidence of combined severe clinical events (renal events, cardiovascular events, cerebrovascular events) in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received Fabrazyme (1 mg/kg every 2 weeks) for up to 5 years3
- Models were run to assess if the incidence of events according to factors associated with severe clinical events were time-dependent3
- Model 1 examined risk factors within the first 6 months (0-0.5 years of Fabrazyme treatment)
- Model 2 examined risk factors within 6 months to 5 years (0.5-5 years of Fabrazyme treatment)
aInformation on the Fabry Registry is voluntary. The Fabry Registry includes patients with a variable range of disease status and management.
bCompared with patients aged <40 years at first ERT, patients aged >40 years at first ERT had a significantly higher risk (based on a Cox proportional hazards regression analysis) of having an event during 0-0.5 year (Model 1: HR 4.4, 95% Cl 2.2 to 8.7, p<0.01), but this decreased during the period >0.5-5 years (Model 2: HR 2.5, 95% Cl 1.7 to 3.8, p<0.01).3
cModel 1: HR 1.1, 95% Cl 0.6 to 2.0, p=0.81.3
dModel 2: HR 1.8, 95% Cl 1.2 to 2.7, p<0.01.3
Indication
References: 1. Banikazemi M et al. Ann Intern Med. 2007;146:77–86. 2. Fabrazyme (agalsidase beta). Prescribing Information. Sanofi. 3. Ortiz A et al. J Med Genet. 2016;53(7):495-502.
