Loargys · 4.8 Undesirable effects · 1

HOS-099741 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most commonly reported adverse reactions in patients in clinical trials were injection site reactions (13.6%) and hypersensitivity (12.5%). Tabulated list of adverse reactions Assessment of adverse reactions was based on exposure in 48 ARG1-D patients (8 adults and 40 children between the ages of 2 and 31 years at enrolment) with treatment duration of up to approximately 5 years across 3 clinical trials. Adverse reactions are listed by MedDRA system organ class and by frequency in Table 1 below. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Due to the small size of the medicinal product safety ARG1-D population database (N=48), the adverse reaction frequency for uncommon, rare and very rare could not be reliably estimated. Table 1. Adverse reactions System organ class Very common Immune system disorders Hypersensitivity General disorders and Injection site reactions administration site conditions Description of selected adverse reactions Hypersensitivity Hypersensitivity reactions with symptoms including facial swelling, rash, flushing and dyspnoea have been reported. In clinical trials, when administered intravenously, 6 of 48 (12.5%) Loargys-treated patients, experienced signs and symptoms either consistent with, or that may be related to a hypersensitivity reaction. The reactions generally occurred with the first few doses. The reactions were mild or moderate and resolved spontaneously, or rapidly after treatment with standard medical care. None of the reactions led to discontinuation of treatment. In the clinical trials, pre-medication with non- sedating antihistamines was considered on an individual basis prior to administration (see section 4.4). Post-marketing, hypersensitivity reactions were reported, even involving patients treated by subcutaneous administration who were pre-medicated with antihistamines. Injection site reactions 6 Injection site reactions were reported in 13.6% (6/44) of Loargys-treated patients after subcutaneous administration. Signs and symptoms included pain, erythema, swelling, irritation and rash at the injection site. The

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HOS-099737 · has-contraindication-information · PDF-Seite 4

Severe hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-099736 · has-indication-information · PDF-Seite 2

Loargys is indicated for the treatment of arginase 1 deficiency (ARG1-D), also known as hyperargininemia, in adults, adolescents and children aged 2 years and older.

HOS-099739 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. Pegzilarginase is a recombinant human enzyme and therefore no cytochrome P450 mediated drug-drug interactions are expected.

HOS-099740 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited data from the use of pegzilarginase in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Pegzilarginase is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding It is unknown whether pegzilarginase is excreted in human or animal milk. A risk to the breastfed new-born/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Loargys therapy taking into account the 5 benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility No human data are available. In animal studies, pegzilarginase produced effects on spermatogenesis and reduced female fertility (see section 5.3).

HOS-099738 · has-warning-information · PDF-Seite 4

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity reactions Hypersensitivity reactions (such as facial swelling, rash, flushing, dyspnoea) have occurred in Loargys treated subjects with intravenous and subcutaneous administration. The reactions generally occurred with the first few doses, but may also occur later in treatment, see section 4.8 for additional details. The initial administrations of Loargys should be performed under medical observation. If a hypersensitivity reaction occurs, appropriate medical treatment should be provided and the patient monitored until signs and symptoms are resolved. The management of hypersensitivity reactions may include temporarily interrupting the administration or lowering the infusion rate and/or treatment with 4 antihistamines and/or corticosteroids. In severe cases stopping the administration and adrenaline treatment may be necessary. Pre-medication with an antihistamine and/or corticosteroid should be considered in patients who previously have developed a hypersensitivity reaction in connection with pegzilarginase treatment. In case of home administration by a non-healthcare professional, the patient should be informed of the early signs of severe hypersensitivity reactions e.g., hives, generalised urticaria, tightness of the chest, wheezing and hypotension. Prescription of medication for treatment of a potential severe hypersensitivity reaction should be considered. Patients should also be advised what to do if symptoms of severe hypersensitivity occur which includes seeking immediate medical support. Monitoring of plasma arginine Pegzilarginase will interfere with routine arginine laboratory analysis, resulting in erroneous low measurements due to post-collection degradation of arginine. The testing laboratory should be informed that the patient is treated with a medicinal product that metabolises and reduces arginine levels. Alternative validated sampling procedures to measure arginine must be used in patients treated with Loargys. This includes CE-marked blood collection tubes containing the enzyme-blocker nor-NOHA. Populations not studied in clinical trials No data from clinical trials are available in middle-age and elderly patients with long-existing motoric impairment, or in patients with arginine levels near

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