IMPORTANT SAFETY INFORMATION: WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. View more

MANUFACTURING LUMIZYME

The manufacture of Lumizyme® (alglucosidase alfa) employs recombinant DNA technology to produce the human GAA enzyme using Chinese hamster ovary (CHO) cells. Production begins with genetic modification of host CHO cells to express the human GAA gene. In brief, the human GAA gene is introduced into an expression vector (DNA construct), which is then inserted into CHO cells.

The genetically-modified CHO cells are then grown (replicated) in steps of increasing bioreactor volumes to achieve the desired cell density and conditions for optimal enzyme production and secretion into a liquid medium. After harvesting the culture medium, the recombinant human GAA enzyme is then isolated using a complex purification process, which includes multiple chromatography and filtration steps.

Product Purity and Safety

The liquid growth medium is sampled daily from the bioreactors to monitor cell growth and quality. After harvesting the culture medium, the GAA enzyme is isolated using a complex purification process, which includes multiple chromatography and filtration steps.

Column filtering systems help eliminate unwanted compounds from the material that contains the enzyme

In order to ensure stability of the final product, it is sterile-filtered, filled into vials, and lyophilized into a powder. Following lyophilization, vials are ready for final quality-control testing, where each lot of Lumizyme undergoes an extensive series of tests to confirm consistent quality before release. To ensure that Lumizyme meets regulatory authority standards and specifications, it is rigorously tested during every stage of manufacturing.

 

Indication

LUMIZYME® (alglucosidase alfa) is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency).

Important Safety Information

WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE

  • Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. Closely observe patients during and after alglucosidase alfa administration and be prepared to manage anaphylaxis and hypersensitivity reactions. Inform patients of the signs and symptoms of anaphylaxis, hypersensitivity reactions, and immune-mediated reactions and have them seek immediate medical care should signs and symptoms occur.
  • Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload, and require additional monitoring.

Warnings and Precautions

Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during and after treatment with alglucosidase alfa. If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue infusion and institute appropriate medical treatment. Appropriate medical support and monitoring measures should be available during infusion.

Immune-Mediated Reactions: Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs. If immune-mediated reactions occur, consider discontinuation of the administration of alglucosidase alfa, and initiate appropriate medical treatment.

Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during alglucosidase alfa infusion, and some patients may require prolonged observation times that should be individualized based on the needs of the patient.

Risk of Cardiac Arrhythmia and Sudden Cardiac Death during General Anesthesia for Central Venous Catheter Placement: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness. Therefore, caution should be used when administering general anesthesia. Ventricular arrhythmias and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy during general anesthesia for central venous catheter placement.

Risk of Antibody Development: Patients with infantile-onset Pompe disease should have a cross-reactive immunologic material (CRIM) assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction in Pompe disease to optimize treatment. CRIM status has been shown to be associated with immunogenicity and patients’ responses to enzyme replacement therapies. There is evidence to suggest that some patients who develop high and sustained IgG antibody titers, including CRIM-negative patients, may experience reduced clinical alglucosidase alfa treatment efficacy.

Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.

Adverse Reactions

The most frequently reported adverse reactions (≥ 5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.

Please see the Full Prescribing Information for complete details, including boxed WARNING.