, Clinical Trial Adverse Reactions). Immune Hypersensitivity reactions including anaphylaxis Hypersensitivity reactions, including anaphylaxis, have been reported in Nexviazyme-treated patients. 6%) patients experienced hypersensitivity reactions including 7 patients who reported severe hypersensitivity reactions and 4 patients who experienced anaphylaxis.
Some of the hypersensitivity reactions were IgE mediated. Anaphylaxis signs and symptoms included hypotension, hypoxia, respiratory distress, chest pressure, generalized edema, flushing, cough, dizziness, nausea, redness on palms, swollen lower lip, decreased breath sounds, feeling hot, erythema, redness on feet, throat tightness, difficulty swallowing (dysphagia), difficulty speaking (dysarthria), pruritis, swollen tongue, itchy palms and feet, and oxygen desaturation.
Symptoms of severe hypersensitivity reactions included swollen tongue, respiratory failure, respiratory distress, generalized edema, erythema, urticaria, and rash. Appropriate medical support measures, including cardiopulmonary resuscitation equipment especially for patients with cardiac hypertrophy and patients with significantly compromised respiratory function, should be readily available when Nexviazyme is administered.
Product Monograph NEXVIAZYME™ avalglucosidase alfa for injection Page 10 of 29 Internal If severe hypersensitivity or anaphylaxis occur, Nexviazyme should be discontinued immediately, and appropriate medical treatment should be initiated.
The risks and benefits of re-administering Nexviazyme following anaphylaxis or severe hypersensitivity reaction should be considered. Some patients have been re-challenged using slower infusion rates at a dose lower than the recommended dose.
In patients with severe hypersensitivity, desensitization procedure to Nexviazyme may be considered. If the decision is made to re-administer the product, extreme caution should be exercised, with appropriate resuscitation measures available.
Once a patient tolerates the infusion, the dose may be increased to reach the approved dose. If mild or moderate hypersensitivity reactions occur, the infusion rate may be slowed or temporarily stopped. Infusion Associated Reactions In clinical studies, IARs were reported to occur at any time during and/or within a few hours after the infusion of Nexviazyme and were more likely with higher infusion rates.
4%) patients treated with Nexviazyme in clinical studies. The majority of IARs were assessed as mild to moderate and symptoms reported in more than one patient included chills, cough, diarrhea, erythema, somnolence, sluggishness, fatigue, pyrexia, flushing, feeling hot or cold, cyanosis and pallor, headache, influenza like illness, nausea, ocular hyperemia, eyelid edema, face edema, pain in extremity, pruritus, rash, rash erythematous, increased or decreased blood pressure, tachycardia, urticaria, vomiting, respiratory distress, chest discomfort, dyspnea, dizziness, hyperhidrosis, skin plaque, lip swelling, oxygen saturation decreased, throat irritation, dyspepsia, burning sensation, pain, palmar erythema, swollen tongue and tremor.
2%) patients reported severe IARs including symptoms of respiratory distress, hypoxia, chest discomfort, generalized edema, tongue edema, dysphagia, nausea, erythema, urticaria, and increased or decreased blood pressure. Patients with an acute underlying illness at the time of Nexviazyme infusion appear to be at greater risk for IARs.
Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from IARs. Antihistamines, antipyretics, and/or corticosteroids can be given to prevent or reduce IARs.
However, IARs may still occur in patients after receiving pre-treatment. If severe IARs occur, immediate discontinuation of the administration of Nexviazyme should be considered and appropriate medical treatment should be initiated.
The benefits and risks of re- administering Nexviazyme following severe IARs should be considered. Some patients have been re- challenged using slower infusion rates at a dose lower than the recommended dose. Once a patient tolerates the infusion, the dose may be increased to reach the approved dose.
If a mild or moderate IARs occur regardless of pre-treatment, decreasing the infusion rate or temporarily stopping the infusion may ameliorate the symptoms. Guide for healthcare professionals (HCPs) for immunosurveillance service A “Guide for healthcare professionals (HCPs) for immunosurveillance service” is available to help manage the following safety concerns for Nexviazyme: • Infusion associated reactions including hypersensitivity and anaphylactic reactions, with or without development of IgG and IgE antibodies • Immunogenicity leading to loss of response (High Sustained IgG Antibody Titers and/or neutralizing antibodies) Product Monograph NEXVIAZYME™ avalglucosidase alfa for injection Page 11 of 29 Internal The guide also provides information about the immunosurveillance service made available by Sanofi in Canada.
ca). Immunogenicity Treatment emergent anti-drug antibodies (ADA) were reported in both treatment naïve (95%) and treatment experienced patients (62%) (see 8 ADVERSE REACTIONS, Clinical Trial Adverse Reactions, Immunogenicity). IARs and hypersensitivity reactions may occur independent of the development of ADA.
The majority of IARs and hypersensitivity reactions were mild or moderate and were managed with standard clinical practices. 3% in patients with […]