Fabrazyme® Clinically Significant Events

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

A chart showing the rate of clinically significant events in Fabrazyme® (agalsidase beta) treated patients vs. placebo treated patients over a 35-month period

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

Image comparing clinical events in patients: 28% in Fabrazyme®-treated group vs. 42% in placebo group

experienced clinical events^a

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 years^3,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

Line graph illustrating the incidence rate per 1,000 patient-years over time, ranging from 0 to 0.5 years up to 4 to 5 years, during Fabrazyme treatment

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 initiated^3,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 thereafter^3,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

Read about safety of Fabrazyme assessed in 4 clinical trials

View Safety →

Indication

Fabrazyme^® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.

Important Safety Information

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS

Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Initiate FABRAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g. anaphylaxis) occurs, discontinue FABRAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions Including Anaphylaxis
In clinical trials and post-marketing experience, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions, some life-threatening, during Fabrazyme infusion. Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion. Consider pretreating with antihistamines, antipyretics, and/or corticosteroids; however, reactions may still occur.

In Fabrazyme clinical trials, some patients developed IgE antibodies or skin test reactivity specific to Fabrazyme.

Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-Fabrazyme antibodies, and in those with high antibody titers compared with antibody negative adult patients.
Consider testing for IgE antibodies in patients who experienced suspected hypersensitivity reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies. Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.

Infusion-Associated Reactions
In Fabrazyme clinical trials, 59% of patients experienced infusion-associated reactions (IARs), some of which were severe. IARs are defined as those occurring on the same day as the infusion. The incidence of these reactions was higher in patients who were positive for anti-Fabrazyme antibodies than those negative for anti-Fabrazyme antibodies.

Consider pretreatment with antipyretics, antihistamines, and/or corticosteroids to reduce the risk of IARs; however, they may still occur.
If a mild or moderate IAR occurs, consider holding the infusion temporarily, decreasing the infusion rate, and/or reducing the Fabrazyme dosage. If a severe IAR occurs, discontinue Fabrazyme immediately and initiate appropriate medical treatment as needed. Assess the risks and benefits of readministering Fabrazyme and monitor patients closely if readministering.
Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from IARs. Closely monitor patients with compromised cardiac function receiving Fabrazyme.

Common Adverse Reactions
Adverse reactions reported (≥20%) were upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness, and rash.

Please see full Prescribing Information, including Boxed WARNING.

Indication

Important Safety Information

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.

Fabrazyme® (agalsidase beta) Efficacy: Effect on Clinically Significant Events

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

43% relative risk reduction of renal, cardiac, and cerebrovascular clinical events and death

A smaller percentage of people had heart, kidney, stroke events, or death.

Study design

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

Study design

Read about safety of Fabrazyme assessed in 4 clinical trials

Indication

Important Safety Information

WARNINGS AND PRECAUTIONS

Indication

Important Safety Information

Fabrazyme^® (agalsidase beta) Efficacy: Effect on Clinically Significant Events

The rate of clinically significant events in Fabrazyme-treated patients vs. placebo-treated patients¹

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 years^3,a