Genzyme Corporate Research Genzyme Websites
Patients and Families Health Care Professionals Contact Us
Aldurazyme Logo
Search

Go
Health Care Professionals
About MPS I
About Aldurazyme
Clinical Pharmacology
Clinical Trials Summary
Indications and Usage
Safety
Dosage and Administration
Importance of Compliance
Payors
Ordering and Reimbursement
Resources and Support
Full Prescribing Information (PDF)

Phase III: Design and Objectives    |    Phase III: Results
Phase III Double-Blind Placebo-Controlled Study Results


Baseline patient characteristics were well balanced between the placebo group (n=23) and the treatment group (n=22). The efficacy evaluations of AldurazymeŽ (laronidase) can be grouped into four categories: pharmacodynamic parameters, respiratory function, functional capacity, and additional endpoints.

Pharmacodynamic parameters:

Urinary GAG levels:

Within 4 weeks, Aldurazyme significantly reduced urinary GAG levels versus placebo

Reduction over several months to near normal age-specific levels

Liver Size:

Mean decrease of 18.9% in Aldurazyme patients versus slight increase (1.3%) in placebo patients after 26 weeks (p=0.001 by ANOVA)


Respiratory function:

Percent of predicted normal FVC (co-primary endpoint)

When FVC was calculated using the patient’s baseline height (i.e., the patient’s height at the first study visit), there was a significant improvement in Aldurazyme patients versus placebo patients (mean difference between groups was 5.6 percentage points, median difference was 3.0 percentage points, p = 0.009 by Wilcoxon rank sum test) at Week 26. Significance testing was performed on the median change.

When FVC was calculated using the patient’s current height at each visit, there was also a significant improvement in Aldurazyme patients versus placebo patients (mean difference between groups was 4 percentage points, p = 0.02) at Week 26. Significance testing was performed on the median change.

Sleep apnea/hypopnea index (AHI; secondary endpoint)

Positive trend toward improvement in apnea/hypopnea index (AHI) versus placebo seen in total intent-to-treat study population (p=0.145)

Significant mean difference of 9 events per hour versus placebo in AHI at 26 weeks (p=0.037, ANOVA) in a subset of patients with sleep apnea at baseline (AHI greater than or equal to 10 events/hour in children and AHI greater than or equal to 15 events/hour in adults).


Functional capacity:

6-minute walk test (6MWT; co-primary endpoint)

Aldurazyme patients had a 38-m mean difference from placebo at 26 weeks (Wilcoxin rank sum, p=0.066)

Shoulder flexion (secondary endpoint)

In the phase III double blind study, patients with severe shoulder restriction (<90.5 degrees of flexion at baseline) showed a positive trend in the ability to raise their arms (shoulder flexion) at 26 weeks; the number of patients in the subanalysis was too small to demonstrate statistical significance

Improvement in the total study group was not statistically significant


If you would like to have more information on clinical trials regarding Aldurazyme, please contact us.

References:
1. Data on file.

2. AldurazymeŽ [package insert]. Novato, CA: BioMarin Pharmaceutical Inc.; 2003 (lines 57-79).
Region/Country
This site is intended for use in the United States. Please visit the Genzyme site for your country or region.
Aldurazyme has been shown to improve pulmonary function and walking capacity in people with MPS I.
MPS I is a progressive, debilitating and often life-threatening disease. Tell us how you found this site and you may help others locate critical information about MPS I and its treatment.

ALDURAZYME® (laronidase) is indicated for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms.  The risks and benefits of treating mildly affected patients with the Scheie form have not been established.

 

ALDURAZYME has been shown to improve pulmonary function and walking capacity.  ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.

 

Important Safety Information

 

WARNING

Risk of anaphylaxis.

Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusions.  Therefore, appropriate medical support should be readily available when ALDURAZYME is administered.  Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring.

 

Life-threatening anaphylactic reactions have been observed in some patients during or up to 3 hours after ALDURAZYME infusions. Reactions have included: respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, airway obstruction, hypoxia, hypotension, bradycardia, and urticaria. Interventions have included: resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and intravenous corticosteroids.

 

In clinical trials and postmarketing safety experience with ALDURAZYME, approximately 1% of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate medical support should be readily available when ALDURAZYME is administered. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation. The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic reaction should be considered.

 

Patients with an acute illness at the time of ALDURAZYME infusion may be at greater risk for infusion-related reactions. Careful consideration should be given to the patient’s clinical status prior to administration of ALDURAZYME.

 

Patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics and/or antihistamines may ameliorate the symptoms.

 

The most common adverse reactions associated with ALDURAZYME treatment in the clinical studies were upper respiratory tract infection, rash, and injection site reaction  The most common adverse reactions requiring intervention were infusion-related reactions involving flushing, fever, headache, and rash. 

 

In postmarketing experience with ALDURAZYME, severe and serious infusion-related reactions have been reported, some of which were life-threatening.  The most frequently reported adverse reactions included: chills, vomiting, nausea, arthralgia, diarrhea, tachycardia, abdominal pain, blood pressure increased, and oxygen saturation decreased. 

 

Approximately 91% of patients treated with ALDURAZYME in clinical studies were positive for antibodies to laronidase. The clinical significance of antibodies to ALDURAZYME is not known, including the potential for product neutralization. Adverse events should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. ALDURAZYME is available by prescription only. To learn more, please see the full prescribing information (PDF) including boxed warning, visit www.ALDURAZYME.com or contact Genzyme at 1-800-745-4447.
Terms and Conditions of Use  |  Privacy Policy  |  This site is intended for United States residents only.
©2003-2009 Genzyme Corporation. All rights reserved. | T/MPSI/US/P090/04/08 		Biomarin Logo Genzyme Logo