Aldurazyme® (laronidase) Clinical Trial Results

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Aldurazyme showed improved respiratory function and walking distance in patients with Mucopolysaccharidosis type I (MPS I).¹

Aldurazyme improved pulmonary function (FVC) in patients with MPS I^1,a,b

In the 26-week, randomized, double-blind, placebo-controlled study, patients treated with Aldurazyme (n=22) experienced a mean 4-point increase in percent predicted forced vital capacity (FVC) compared with those receiving placebo (n=23) (median difference 2.0 [95% CI:0.4, 7] p=0.02).¹

Study 1 was a randomized, double-blind, placebo-controlled study in 45 patients with MPS I, aged 6 to 43 years, including 1 patient with the Hurler form, 37 patients with Hurler-Scheie form, and 7 patients with Scheie form of MPS I. All patients had a baseline percent predicted FVC less than or equal to 77%. Patients received Aldurazyme at 0.58 mg/kg of body weight once weekly or placebo once weekly for 26 weeks. All patients were treated with antipyretics and antihistamines prior to each infusion. The primary efficacy outcome assessments were percent predicted FVC and distance walked in 6 minutes (6-MWT).¹

Mean change over time in FVC values²

Graph showing the mean change in % of predicted forced vital capacity (FVC) from baseline over a 26 week period in patients receiving Aldurazyme® (laronidase) versus placebo

Mean pretreatment baseline for FVC (percent of a predicted normal) was 48 ± 15 for the Aldurazyme arm and 54 ± 16 for the placebo arm¹
Mean Week 26 FVC was 50 ± 17 for the Aldurazyme arm and 51 ± 13 for the placebo arm¹

^aThe risks and benefits of treating mildly affected patients with the Scheie form have not been established.
^bAldurazyme has not been evaluated for its effects on the central nervous system manifestations of the disorder.
^cWilcox Rank Sum Test on median of difference.

Aldurazyme improved walking distance (6-MWT) in patients with MPS I^1,a,b

In the 26-week, randomized, double-blind, placebo-controlled study, patients treated with Aldurazyme (n=22) showed a mean 38-meters increase in distance walked (as measured by the 6-MWT) compared with those receiving placebo (n=23) (median difference 39 [95% CI: -2.0, 79.0] p=0.07).^1,3

Study 1 was a randomized, double-blind, placebo-controlled study in 45 patients with MPS I, ages 6 to 43 years old, including 1 patient with the Hurler form, 37 patients with Hurler-Scheie form, and 7 patients with Scheie form of MPS I. All patients had a baseline percent predicted forced vital capacity (FVC) less than or equal to 77%. Patients received Aldurazyme at 0.58 mg/kg of body weight once weekly or placebo once weekly for 26 weeks. All patients were treated with antipyretics and antihistamines prior to each infusion. The primary efficacy outcome assessments were percent predicted FVC and distance walked in 6 minutes (6-MWT).

Mean change over time in distance walked³

Graph showing the mean change in 6 minute walk test distance in meters from baseline over a 26 week period in patients receiving Aldurazyme® (laronidase) versus placebo

Mean pretreatment baseline for the 6-MWT distance in meters was 319 ± 131 for the Aldurazyme arm and 367 ± 114 for the placebo arm¹
Mean week 26 6-MWT distance in meters was 339 ± 127 for the Aldurazyme arm and 348 ± 129 for the placebo arm¹

For patients treated with Aldurazyme, the mean increase in the 6‑MWT distance was maintained for an additional 182 weeks through the completion of Study 2.¹

Aldurazyme decreased urinary glycosaminoglycan (GAG) level by 54%³^,a,b

Results from a randomized, double‑blind, placebo-controlled study of 45 MPS I patients (aged 6 to 43 years) measuring mean change over time in urinary GAG level (n=22 and 23 for the placebo group and n=21 and 22 for the Aldurazyme group, respectively, at baseline and week 26).

Study 1 Design

Study 2 Design

Study 2 was a 182-week, open-label, uncontrolled extension study of all 45 patients who completed Study 1. Patients received Aldurazyme at 0.58 mg/kg body weight once weekly.

Mean change over time in urinary glycosaminoglycan (GAG) levels

Graph showing the change in mean urinary glycosaminoglycan (GAG) levels in ug/mg creatinine from baseline over a 26 week period in patients receiving Aldurazyme® (laronidase) versus a placebo

Urinary GAG levels decreased in patients treated with Aldurazyme compared to placebo. No patients in the group receiving Aldurazyme reached the normal range for urinary GAG levels during this six-month study¹

At the end of Study 2, the decrease in mean urinary GAG was similar to the decrease in urinary GAG reported in the Aldurazyme-treated patients at the end of Study 1.¹

The relationship of urinary GAG to other measures of clinical response has not been established.¹

6-MWT=six-minute walk test; FVC=forced vital capacity; GAG=glycosaminoglycan; MPS I=mucopolysaccharidosis type I.

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Indication

ALDURAZYME^® (laronidase) is indicated for the treatment of adult and pediatric 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.

Limitations of Use:

The safety and effectiveness of treating mildly affected patients with the Scheie form have not been established.
The effect of ALDURAZYME on central nervous system manifestations of the disorder has not been determined.

Important Safety Information

WARNING: HYPERSENTIVITIY REACTIONS INCLUDING ANAPHYLAXIS, and ACUTE RESPIRATORY COMPLICATIONS ASSOCIATED WITH ADMINISTRATION

Hypersensitivity Reactions Including Anaphylaxis
Patients treated with ALDURAZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during ALDURAZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ALDURAZYME immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reactions, a desensitization procedure to ALDURAZYME may be considered.

Acute Respiratory Complications Associated with Administration
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.

Warnings and Precautions
Hypersensitivity Reactions Including Anaphylaxis: See Boxed WARNING.

Pre-existing upper airway obstruction may contribute to the severity of some reactions. Consider premedicating patients with antihistamines, with or without antipyretics. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
Consider risks and benefits of re-administering ALDURAZYME following severe hypersensitivity reactions. Patients may be rechallenged using slower infusion rates which may be increased if tolerated to reach the recommended rate. If a mild or moderate hypersensitivity reaction occurs, consider temporarily holding the infusion or slowing the infusion rate.

Acute Respiratory Complications Associated with Administration: See Boxed WARNING.

Patients with an acute febrile or respiratory illness may be at greater risk for infusion reactions. Consider the patient’s clinical status prior to administration of ALDURAZYME and consider delaying the infusion.
Evaluation of airway patency should be considered prior to initiating ALDURAZYME. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction or extreme drowsiness/sleep induced by antihistamine use.

Acute Cardiorespiratory Failure:

Use caution when administering ALDURAZYME to patients susceptible to fluid overload, or with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. Consider a decreased total infusion volume and infusion rate when administering ALDURAZYME to these patients.

Infusion-Associated Reactions:

ALDURAZYME may cause infusion-associated reactions (IARs). Consider pre-medicating with antihistamines, with or without antipyretics, however IARs may still occur in patients after receiving pre-medication. Discontinue immediately or adjust the infusion rate based on the severity of the reaction.

Adverse Reactions
Patients 6 months of age and older

The most common adverse reactions reported in ≥10% of patients were infusion reactions, which included pyrexia, chills, blood pressure increased, tachycardia, and oxygen saturation decreased.

Patients 6 years of age and older

The most common adverse reactions reported in ≥10% of patients were rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, and poor venous access.

Please see Full Prescribing Information including Boxed WARNING for Aldurazyme.

Indication

Important Safety Information

References: 1. Aldurazyme (laronidase). Prescribing Information. Sanofi. 2. Data on file. Genzyme Corporation. 3.Wraith JE et al. J Pediatr. 2004;144(5):581-588.

Aldurazyme® (laronidase) Clinical Trial Results

Aldurazyme showed improved respiratory function and walking distance in patients with Mucopolysaccharidosis type I (MPS I).1

Aldurazyme improved pulmonary function (FVC) in patients with MPS I1,a,b

Study 1 Design

Mean change over time in FVC values2

Aldurazyme improved walking distance (6-MWT) in patients with MPS I1,a,b

Study 1 Design

Mean change over time in distance walked3

Study 2 Design

For patients treated with Aldurazyme, the mean increase in the 6‑MWT distance was maintained for an additional 182 weeks through the completion of Study 2.1

Aldurazyme decreased urinary glycosaminoglycan (GAG) level by 54%3,a,b

Study Designs

Mean change over time in urinary glycosaminoglycan (GAG) levels

Explore Aldurazyme safety

Indication

Limitations of Use:

Important Safety Information

Indication

Important Safety Information

Aldurazyme^® (laronidase) Clinical Trial Results

Aldurazyme showed improved respiratory function and walking distance in patients with Mucopolysaccharidosis type I (MPS I).¹

Aldurazyme improved pulmonary function (FVC) in patients with MPS I^1,a,b

Mean change over time in FVC values²

Aldurazyme improved walking distance (6-MWT) in patients with MPS I^1,a,b

Mean change over time in distance walked³

For patients treated with Aldurazyme, the mean increase in the 6‑MWT distance was maintained for an additional 182 weeks through the completion of Study 2.¹

Aldurazyme decreased urinary glycosaminoglycan (GAG) level by 54%³^,a,b