Lumizyme is medication that replaces the enzyme acid alfa glucosidase (GAA), which is missing or deficient in people with late (non-infantile) onset Pompe disease, the form of Pompe disease that is generally diagnosed after infancy. Since people with Pompe disease do not produce enough of the GAA enzyme on their own, a regular supply of the replacement enzyme may help manage the disease in some patients.
Lumizyme is an enzyme replacement therapy (ERT) produced using recombinant DNA technology, a process that enables animal cells to produce human enzymes. The genetically engineered enzyme is intended to act like the naturally occurring GAA that is normally produced within human cells. Treatment with Lumizyme is not a cure for Pompe disease; that is, it may provide a long-term, ongoing replacement for the missing enzyme, but it will not correct the underlying genetic defect that causes the enzyme deficiency.
Lumizyme is indicated for patients 8 years and older with late (non-infantile) onset Pompe disease who do not have evidence of an enlarged heart. The safety and efficacy of Lumizyme have not been tested in clinical studies in infantile-onset patients or in late (non-infantile) onset patients less than 8 years of age.
Patients 8 years and older may still receive Lumizyme if they have an enlarged heart resulting from conditions unrelated to their Pompe disease.
Life-threatening severe allergic (anaphylactic) reactions have occurred in some patients during Lumizyme infusions and up to 3 hours after Lumizyme infusion. Your doctor should have appropriate medical support measures, including cardiopulmonary (heart/lung) resuscitation equipment readily available during your Lumizyme infusion.
If you experience severe allergic reactions, your doctor may stop the infusion and will provide appropriate medical care.
Severe skin-related (cutaneous) and other immune system-related reactions can occur within several weeks to 3 years after starting treatment with Lumizyme. Your doctor should monitor you for the development of reactions involving skin and other organs.
INDICATION
LUMIZYME® (alglucosidase alfa) is a medication that replaces the missing or deficient enzyme in patients who are 8 years and older with late-onset (non-infantile) Pompe disease (also known as GAA deficiency) who do not have an enlarged heart. The safety and effectiveness of LUMIZYME have not been tested in clinical studies of infantile-onset patients or patients with late (non-infantile) onset Pompe disease who are less than 8 years old.
IMPORTANT SAFETY INFORMATION
WARNING
Some patients have experienced life-threatening severe allergic (anaphylactic) reactions (hives, problems breathing, low blood pressure, throat and lip swelling), or severe skin reactions (e.g. deep skin tissue reaction with open sore) and systemic immune mediated reactions (e.g. kidney problems and skin rashes) during LUMIZYME infusions. Therefore, appropriate medical support measures should be readily available during your LUMIZYME infusion.
Because there is a risk that the disease may progress rapidly in Pompe disease patients who are less than 8 years old, LUMIZYME is available only through a restricted distribution program called the LUMIZYME ACE Program. Only prescribers and healthcare facilities who are enrolled in this program may prescribe, dispense or administer LUMIZYME, and only patients who have been enrolled in the program by their doctors and meet all of the conditions of the program may receive LUMIZYME. Speak with your doctor for more information about how to enroll.
Anaphylaxis and Allergic Reactions Anaphylaxis (a severe, and possibly life-threatening, allergic reaction) and severe allergic reactions have been observed in patients during and up to 3 hours after Lumizyme infusion. Some of the reactions were life-threatening, and included anaphylactic shock, respiratory arrest (stops breathing), apnea (stops or decreases breathing), dyspnea (shortness of breath), bradycardia (slow heartbeat), tachycardia (fast heartbeat), and hypotension (low blood pressure). Other reactions included chest discomfort/pain, throat tightness, bronchospasm (tightening of the airways/difficulty breathing), wheezing, tachypnea (rapid breathing), cyanosis (a blue coloring of the skin due to diminished oxygen), decreased oxygen in the blood, convulsions, swelling (including tongue or lip swelling, puffiness of the eyes, and face swelling), itching, rash, hives, increased sweating, nausea, dizziness, hypertension (high blood pressure), flushing/erythema (redness of the skin), fever, pallor (pale coloring to the skin), feeling cold, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia (tingling or numbness of the skin).
If these reactions occur, your doctor may stop the infusion and will provide appropriate medical care. This may include interruption of the infusion or the administration of antihistamines (anti-allergic medications), corticosteroids, intravenous fluids, and/or oxygen. In some cases of anaphylaxis, epinephrine has been given. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary (heart/lung) resuscitation equipment, should be readily available when Lumizyme is administered. Your doctor will consider the risks and benefits of re-administering Lumizyme following an anaphylactic or severe allergic reaction.
Immune System-Related Reactions Severe cutaneous (skin-related) reactions and immune system-related reactions have been reported with Lumizyme. These reactions occurred several weeks to 3 years after the start of Lumizyme infusions. You should be monitored for the development of possible immune system-related reactions involving skin and other organs while receiving Lumizyme. If such reactions occur, your doctor will stop the Lumizyme infusion and will consider the risks and benefits before starting the infusions again. Some patients who have experienced these types of reactions have successfully been retreated with Lumizyme under the close supervision of their doctor.
Risk of Severe Cardiorespiratory (Heart/Lung) Failure Patients who have a severe respiratory (breathing-related) illness or whose heart and lungs may not be working as they should may be at risk for a serious worsening of their heart or breathing problems during infusions with Lumizyme. For this reason, your doctor will be sure that you are carefully monitored and that appropriate medical support is available during your infusion. Some patients may need to be monitored for longer periods.
Precautions for General/Regional Anesthesia Giving general anesthesia to patients who have severe heart and skeletal (including breathing-related) muscle weakness can be risky. Therefore, your doctor will use extreme caution if you need to receive anesthesia.
Monitoring: Laboratory Tests Your doctor will monitor you regularly and give you regular blood tests to check for immune system-related and other side effects while you are receiving Lumizyme. This includes testing for antibody formation every 3 months for 2 years and then annually thereafter.
Adverse Reactions Serious adverse reactions (side effects) reported with Lumizyme in a clinical study included anaphylaxis. Anaphylactic reactions included: angioedema (swelling under the skin or of the throat and tongue), throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia (rapid heart rate). Other serious adverse events that occurred in a higher incidence in Lumizyme-treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis (irritation and inflammation of the digestive tract), and dehydration.
The most common adverse reactions observed in clinical studies were infusion reactions. Infusion reactions that occurred in Lumizyme-treated patients at an incidence of ≥5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea (shortness of breath), pruritus (intense itching), rash/erythema, pharyngolaryngeal (throat) pain, neck pain, hypoacusis (partial hearing loss), flushing/feeling hot, pain in extremity (arms or legs), fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with Lumizyme included respiratory distress, cough, livedo reticularis (purplish lace-pattern of the skin), agitation, irritability, retching, rigors (chills), tremor and increased lacrimation (excessive watering of the eyes). Infusion reactions may occur during or within 2 hours after completion of the infusion.
Some patients have experienced delayed infusion reactions. This means they had a reaction within 48 hours of the infusion. Your doctor will let you know about the possibility of having delayed infusion reactions and will also give you follow-up instructions so that you know what to do if you experience them.
If you experience severe allergic reactions, your doctor will immediately stop the infusion and start appropriate medical treatment. If an infusion reaction occurs, it is managed by decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines (anti-allergic medications) and/or antipyretics (fever-reducing medications) may help the symptoms. Patients who have experienced infusion reactions should be treated with caution when they are re-administered Lumizyme.
In postmarketing experience with Lumizyme, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with Lumizyme treatment included cardiorespiratory (heart and lung) arrest, respiratory failure, hemothorax (blood in the chest cavity), pneumothorax (air outside the lungs in the chest cavity), cardiac failure, sepsis (bacteria in the blood), aortic dissection (a tear in the wall of the aorta), cerebrovascular accident (stroke), and skin necrosis (death of skin cells). The most frequently reported serious adverse reactions were infusion reactions. The following serious adverse events have been reported in at least 2 patients: dyspnea (shortness of breath), respiratory failure, bronchospasm, stridor (whistling sound while breathing which indicates an obstruction), hypoxia (not enough oxygen in the blood), pharyngeal edema (throat swelling), chest discomfort, chest pain, hypotension, hypertension, erythema (redness of the skin), flushing, lung infection, tachycardia, cyanosis, and hypersensitivity (allergic reaction). One case of hyperparathyroidism (a condition in which the parathyroid gland produces too much of a certain hormone) has been reported.
Immunogenicity (Immune-related) In the clinical study, all patients with available samples treated with Lumizyme developed IgG (specific) antibodies against alglucosidase alfa. Antibodies are an indicator of an immune response to a drug (your body recognizing and defending itself from substances that appear foreign). All patients who developed IgG antibodies did so within the first 3 months of treatment.
A small number of Lumizyme-treated patients in clinical trials and postmarketing setting who were evaluated tested positive for presence of Lumizyme-specific IgE antibodies (associated with a reaction). Some of these patients experienced anaphylaxis. Some patients who tested positive for Lumizyme-specific IgE antibodies were successfully retreated with Lumizyme using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision. Patients who develop IgE antibodies to Lumizyme appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions. Therefore, these patients should be monitored more closely during administration of Lumizyme.
To report suspected adverse reactions contact Genzyme Medical Information at 800-745-4447, option 2.
Please see the full prescribing information for complete details, including boxed warning.