MPS I Disease Overview | Aldurazyme®

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MPS I is a rare, genetic, debilitating, multisystemic lysosomal storage disease.^1,2

Marked by heterogeneity, MPS I presents with a broad range of progressive manifestations and seemingly unrelated symptom combinations.^3,4

Patients with MPS I produce the enzyme in low amounts or not at all³

MPS I is a progressive disease caused by pathogenic variants in the IDUA gene leading to deficiency or complete lack of lysosomal enzyme IDUA. This deficiency in enzyme activity can result in widespread cellular, tissue, and organ dysfunction, which can be potentially life-threatening.³

MPS I can be severe and potentially life-threatening^2,4

Without disease management, patients with the severe phenotype (Hurler) usually die within the first decade of life as a result of cardiorespiratory failure and progressive neurologic disease.⁴

Without disease management, patients with the attenuated phenotype (Hurler-Scheie/Scheie) may have a normal or near-normal life span but may be burdened by considerable morbidity.⁴

Patients with Hurler-Scheie (H/S) syndrome may face premature death by the age of 30 years.⁴

IDUA=α-L-iduraonidase.

Patients with MPS I face a multitude of serious and often-debilitating multisystemic manifestations^1,2

In MPS I, the IDUA enzyme is deficient or essentially absent, causing GAG substrates^a to accumulate in the cells, which can lead to progressive damage to tissues and organs.

Progressive, multisystemic, potentially irreversible tissue damage can lead to loss of function, clinical deterioration, and a variety of manifestations.

Some common manifestations include:

Illustration showing some common manifestations of MPS I including coarse facial features, corneal clouding, hepatosplenomegaly, musculoskeletal abnormalities, cardiac valve abnormalities, airway-related symptoms, and cognitive impairment in more severe forms.

^aThe GAGs that accumulate in MPS I are dermatan sulfate and heparan sulfate.
^bScheie form has no cognitive impairment/normal cognitive function.

Classification of MPS I^3,4

MPS I is classified into 3 different syndromes based on the age of onset, severity of symptoms, and rate of disease progression.^3,4

MPS I represents a spectrum of disease³
	Severe MPS I Rapid progression	Attenuated MPS I Slower progression
Phenotype	Hurler	Hurler-Scheie	Scheie
Median Age of Onset⁴	6 months	1.8 years	5.3 years
Common Symptoms	Hernia, coarse facial features, kyphosis/gibbus, hepatomegaly, and corneal clouding	Hernia, corneal clouding, hepatomegaly, coarse facial features, and cardiac valve abnormalities	Hernia, joint contractures, corneal clouding, cardiac valve abnormalities, and carpal tunnel syndrome
Median Age at Diagnosis⁴	1 year	4 years	9.4 years
Impact of Cognition	Pronounced mental delay with the loss of acquired skills	No/mild mental delay, learning disabilities	None

All patients with MPS I are at risk of significant, multisystemic disease

In severe MPS I

Patients with “severe” MPS I suffer from several debilitating symptoms, including cognitive impairment, that progress rapidly.^3,4

In attenuated MPS I

Patients with “attenuated” MPS I have milder symptoms and slower disease progression compared with Hurler syndrome. But they can still experience significant disease-related morbidity.^3,4

CNS=central nervous system; GAG=glycosaminoglycan; H/S syndrome=Hurler-Scheie syndrome; IDUA=α-L-iduronidase; 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. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human α-L-iduronidase (laronidase). J Pediatr. 2004;144(5):581-588. 2. D’Aco K, Underhill L, Rangachari L, et al. Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry. Eur J Pediatr. 2012;171(6):911-919. 3. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed July 20, 2022. https://ommbid.mhmedical.com/content.aspx?bookid=2709&ectionid=225544161. 4. Beck M, Arn P, Giugliani R, et al. The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med. 2014;16(10):759-765. 5. Muenzer J, Wraith JE, Clarke LA; International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009;123(1):19-29. 6. Wraith JE. The first 5 years of clinical experience with laronidase enzyme replacement therapy for mucopolysaccharidosis I. Expert Opin Pharmacother. 2005;6(3):489-506.

Mucopolysaccharidosis type I (MPS I) Disease Overview

MPS I is a rare, genetic, debilitating, multisystemic lysosomal storage disease.1,2

Patients with MPS I produce the enzyme in low amounts or not at all3

MPS I can be severe and potentially life-threatening2,4

Patients with MPS I face a multitude of serious and often-debilitating multisystemic manifestations1,2

Some common manifestations include:

Classification of MPS I3,4

MPS I represents a spectrum of disease3

All patients with MPS I are at risk of significant, multisystemic disease

In severe MPS I

In attenuated MPS I

Speak with a representative–We're here to help you get answers

Disease management resources for you and your patients

Indication

Limitations of Use:

Important Safety Information

Indication

Important Safety Information

MPS I is a rare, genetic, debilitating, multisystemic lysosomal storage disease.^1,2

Patients with MPS I produce the enzyme in low amounts or not at all³

MPS I can be severe and potentially life-threatening^2,4

Patients with MPS I face a multitude of serious and often-debilitating multisystemic manifestations^1,2

Classification of MPS I^3,4

MPS I represents a spectrum of disease³