Hypersensitivity Reactions Including Anaphylaxis

Patients treated with XENPOZYME have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, XENPOZYME should be discontinued immediately and appropriate medical treatment should be initiated. In patients with severe hypersensitivity reaction, a desensitization procedure to XENPOZYME may be considered.

Prior to XENPOZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration.

If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of readministering XENPOZYME following severe hypersensitivity reactions (including anaphylaxis). One patient has been rechallenged using slower infusion rates at a dosage lower than the recommended dosage. In patients with severe hypersensitivity reaction, a tailored desensitization procedure to XENPOZYME may be considered. If the decision is made to readminister XENPOZYME, ensure the patient tolerates the infusion. If the patient tolerates the infusion, the dosage (dose and/or the rate) may be increased to reach the approved recommended dosage.

If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dose reduced [see Dosage and Administration (2.5)].

Hypersensitivity reactions, including anaphylaxis, have been reported in olipudase alfa-treated patients. One 18-month-old XENPOZYME-treated patient experienced an anaphylactic reaction during the sixth infusion in the dose escalation period in Trial 2 [see Adverse Reactions (6.1)]. Additionally, a 16-month-old patient with ASMD type A, treated with a version of olipudase alfa manufactured from a different process, experienced two anaphylactic reactions during the fifth and sixth infusions in the dose escalation period; the patient received an immune tolerance induction therapy prior to treatment. In both of these pediatric patients who had anaphylaxis, anti-olipudase alfa-rpcp IgE (IgE ADA) and IgG (IgG ADA) antibodies were detected [see Adverse Reactions (6.1) and Clinical Pharmacology (12.6)].

Hypersensitivity related reactions that were mild to moderate in severity occurred in 10 (33%) XENPOZYME-treated adult patients and 4 (50%) XENPOZYME-treated pediatric patients in clinical trials. Hypersensitivity reactions in adults included urticaria, pruritus, erythema, rash, rash erythematous, eczema, angioedema and erythema nodosum. Hypersensitivity reactions in pediatric patients included urticaria, pruritus, rash, erythema and localized edema [see Adverse Reactions (6)]. 

• Consider testing for IgE ADA in XENPOZYME-treated patients who experienced severe hypersensitivity reactions, including anaphylaxis [see Adverse Reactions (6.1)]. Testing for antibodies against olipudase alfa-rpcp are available through Genzyme Corporation (at 1-800-745-4447).
• Consider other clinical laboratory testing such as serum tryptase and complement activation in patients who experience anaphylaxis.