Pompe disease is a rare inherited neuromuscular disorder that causes progressive muscle weakness in people of all ages. Pompe disease is caused by a defective gene that results in a deficiency of an enzyme, acid alpha-glucosidase (pronounced “AL-fa glue-CO-sih-days” and often abbreviated GAA). The absence of this enzyme results in excessive buildup of a substance called glycogen, a form of sugar, in a specialized compartment of muscle cells throughout the body.
Signs & Symptoms of Pompe Disease
Although the effects of Pompe disease vary from patient to patient, some generalizations can be made. Most patients experience muscle weakness in the arms and legs, usually most prominently in the legs, making walking or climbing stairs difficult. Muscles used for breathing may frequently be affected, making it difficult to breathe, especially when lying down. In infants, the heart is usually affected, resulting in greatly enlarged heart and other heart problems.
Diagnosing Pompe Disease
After examining a patient’s symptoms and reviewing the results of several different tests, doctors may ultimately come to suspect Pompe disease. A conclusive way to confirm this diagnosis is by measuring the activity of the acid alpha-glucosidase (GAA) enzyme, which is always lower than normal in people with Pompe disease. The test used for this is called an enzyme assay. Today, enzyme assays can be performed with simple blood tests that provide fast and accurate results.
Pompe Disease Inheritance
Although Pompe disease is very rare, it can
be inherited, meaning that it gets passed on to people through their parents. If someone is diagnosed with the disease, there is a risk that relatives may also have the disease or be carriers. The symptoms of Pompe disease can emerge very slowly and at any age, so it is possible for someone to have it even if they are not experiencing any apparent problems. Because early diagnosis is so important in managing the disease, families with a history of it may want to consider several testing options.
Living with Pompe Disease
Although Pompe disease is rare, there are active patient groups and caring health professionals throughout the world who can help patients and their families manage the challenges of living with this disease.
MYOZYME (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency). MYOZYME has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of MYOZYME in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.
Important Safety Information
WARNING: ANAPHYLAXIS, SEVERE ALLERGIC AND IMMUNE MEDIATED REACTIONS AND RISK OF CARDIORESPIRATORY FAILURE
Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during MYOZYME infusions. Therefore, appropriate medical support should be readily available when MYOZYME is administered.
Risk of Cardiorespiratory Failure:
Patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to infusion reactions, and require additional monitoring.
Anaphylaxis and Allergic Reactions: Anaphylaxis and severe allergic reactions have been reported in some patients during and up to three hours after MYOZYME infusion, some of which were IgE-mediated. Some of the reactions were life-threatening and included: anaphylactic shock, cardiac arrest, respiratory distress, hypotension, bradycardia, hypoxia, bronchospasm, throat tightness, dyspnea, angioedema, and urticaria. Interventions have included: cardiopulmonary resuscitation, mechanical ventilatory support, oxygen supplementation, intravenous (IV) fluids, hospitalization, treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.
In clinical trials and postmarketing safety experience with MYOZYME, approximately 1% of patients developed anaphylactic shock and/or cardiac arrest during MYOZYME infusion that required life-support measures. In clinical trials and expanded access programs with MYOZYME, approximately 14% of patients treated with MYOZYME have developed allergic reactions that involved at least 2 of 3 body systems, cutaneous, respiratory or cardiovascular systems. These events included: Cardiovascular: hypotension, cyanosis, hypertension, tachycardia, ventricular extrasystoles, bradycardia, pallor, flushing, nodal rhythm, peripheral coldness; Respiratory: tachypnea, wheezing/bronchospasm, rales, throat tightness, hypoxia, dyspnea, cough, respiratory tract irritation, decreased oxygen saturation; Cutaneous: angioedema, urticaria, rash, erythema, periorbital edema, pruritus, hyperhidrosis, cold sweat, livedo reticularis.
If anaphylactic or other severe allergic reactions occur, immediate discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment should be initiated. Because of the potential for severe allergic reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME is administered. The risks and benefits of re-administering MYOZYME following an anaphylactic or severe allergic reaction should be considered. Some patients have been rechallenged and have continued to receive MYOZYME under close clinical supervision. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product
Immune Mediated Reactions: Severe cutaneous and systemic immune mediated reactions have been reported in postmarketing safety experience with MYOZYME in at least 2 patients, including ulcerative and necrotizing skin lesions, and possible type III immune mediated reactions. These reactions occurred several weeks to 3 years after initiation of MYOZYME infusions. Skin biopsy in one patient demonstrated deposition of anti-rh-GAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in a few Pompe patients treated with alglucosidase alfa and who had persistently positive anti-rhGAA IgG antibody titers. In these patients renal biopsy was consistent with immune complex deposition. Patients improved following treatment interruption. It is therefore recommended to perform periodic urinalysis. Patients should be monitored for the development of systemic immune mediated reactions involving skin and other organs while receiving MYOZYME. If immune mediated reactions occur, discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.
Risk of Acute Cardiorespiratory Failure: Acute cardiorespiratory failure requiring intubation and inotropic support has been observed up to 72 hours after infusion with MYOZYME in infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of MYOZYME. Patients with acute underlying respiratory illness, compromised cardiac function and/or sepsis 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 MYOZYME infusion, and infants with cardiac dysfunction 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 for the placement of a central venous catheter intended for MYOZYME infusion. 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.
Infusion Reactions: Infusion reactions occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies. Severe infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: fever, decreased oxygen saturation, tachycardia, cyanosis and hypotension. Other infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure/hypertension, cyanosis, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness and wheezing. Some patients were pre-treated with antihistamines, antipyretics and/or steroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, or steroids. Infusion reactions may occur at any time during, or up to 2 hours after, the infusion of MYOZYME, and are more likely with higher infusion rates. The risks and benefits of re-administering MYOZYME following an anaphylactic or severe allergic reaction should be considered. Some patients have been rechallenged and have continued to receive MYOZYME under close clinical supervision. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from infusion reactions. Therefore, these patients should be monitored more closely during administration of MYOZYME. Patients with an acute illness at the time of MYOZYME infusion may be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of MYOZYME. If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment should be initiated.
Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.
The most serious adverse reactions reported with MYOZYME were anaphylactic reactions, acute cardiorespiratory failure, and cardiac arrest. Anaphylactic reactions have been reported during and within 3 hours after MYOZYME infusion. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa. Infusion reactions, defined as an adverse reaction occurring during the infusion or within 2 hours after completion of the infusion, that occurred in more than 1 patient in clinical studies and the expanded access program include rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturations, vomiting, tachypnea, agitation, increased blood pressure/hypertension, cyanosis, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness, and wheezing. In addition to the infusion reactions reported in clinical trials and expanded access programs, the following infusion reactions have been reported in patients during postmarketing use of MYOZYME: cardiac arrest, respiratory arrest, apnea, stridor, pharyngeal edema, peripheral edema, chest pain, chest discomfort, muscle spasm, fatigue and conjunctivitis. Additional adverse drug reactions included proteinuria and nephrotic syndrome.
Immunogenicity: The majority of patients (34 of 38; 89%) in the two clinical trials tested positive for IgG antibodies to alglucosidase alfa. Most patients who develop antibodies do so within the first 3 months of exposure. There is evidence to suggest that patients developing sustained titers =12,800 of anti-alglucosidase alfa antibodies may have a poorer clinical response to treatment, or may lose motor function as antibody titers increase. Five patients with antibody titers = 12,800 at Week 12 had an average increase in clearance of 50% from Week 1 to Week 12. The effect of antibody development on the long-term efficacy of MYOZYME is not fully understood. However, CRIM-negative infants have shown poorer clinical response in the presence of high sustained IgG antibody titers and inhibitory and positive inhibitory antibodies. Patients who develop IgE antibodies to alglucosidase alfa 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 MYOZYME.
To report suspected adverse reactions contact Genzyme Medical Information at 800-745-4447, option 2.
Please see full prescribing information for complete details, including boxed warning.