2% of patients. 5%) experienced a serious reaction that was considered related to pegunigalsidase alfa. Four of these reactions were confirmed IgE-mediated hypersensitivity (bronchospasm, hypersensitivity) that occurred at the first infusion of pegunigalsidase alfa and resolved within the day after occurrence.
Tabulated summary of adverse reactions The data described below reflects data from 141 patients with Fabry disease who received pegunigalsidase alfa in 8 clinical studies, following the posology of 1 mg/kg every two weeks or 2 mg/kg every four weeks for a minimum of 1 infusion up to 7 years.
Adverse reactions are listed in Table 3. Information is presented by system organ class. 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); frequency not known (cannot be estimated from available data).
Table 3:
Adverse reactions reported during treatment with pegunigalsidase alfa System organ class Frequency Common Uncommon Immune system disorders hypersensitivity* type I hypersensitivity* Psychiatric disorders agitation* insomnia Nervous system disorders paraesthesia* dizziness* headache* restless legs syndrome peripheral neuropathy neuralgia burning sensation tremor* syncope* Ear and labyrinth disorders vertigo Vascular disorders flushing hypotension* hypertension* lymphoedema 8 System organ class Frequency Common Uncommon Respiratory, thoracic and mediastinal disorders bronchospasm* sneezing* nasal congestion* dyspnoea* throat irritation* throat tightness Gastrointestinal disorders nausea* abdominal pain* diarrhoea vomiting* gastrooesophageal reflux disease gastritis dyspepsia flatulence Skin and subcutaneous issue disorders rash* erythema* pruritus* hypohidrosis Musculoskeletal and connective tissue disorders arthralgia musculoskeletal pain* Renal and urinary disorders membranoproliferative glomerulonephritis chronic kidney disease proteinuria Reproductive system and breast disorders nipple pain General disorders and administration site conditions asthenia* chills* chest pain* pain* influenza-like illness infusion site extravasation infusion site pain oedema Investigations body temperature increased* urine protein/creatinine ratio increased white blood cells urine positive blood uric acid increased weight increased Injury, poisoning and procedural complications infusion related reaction* Cardiac disorders supraventricular extrasystoles The following preferred terms have been grouped in Table 3: • hypersensitivity includes: drug hypersensitivity • agitation includes: nervousness • abdominal pain includes: abdominal discomfort • rash includes: rash maculo-papular and rash pruritic • musculoskeletal stiffness recorded as musculoskeletal pain includes: myalgia • asthenia includes: malaise and fatigue • chest pain includes: chest discomfort and non-cardiac chest pain • pain includes: pain in extremity • oedema peripheral recorded as oedema * Preferred terms considered as IRR as described in the section below.
Description of selected adverse reactions Infusion related reactions (adverse reactions within 2 hours of infusion) IRRs were reported in a total of 36 patients (25%): 26 patients (23%) treated with 1 mg/kg every two weeks and 10 patients (34%) treated with 2 mg/kg every four weeks.
The most commonly reported symptoms associated with IRRs reported for 1 mg/kg dosage were: hypersensitivity, chills, dizziness, rash and itching. For the 2 mg/kg dose the most commonly reported symptoms were pain, headache and nausea.
IRRs were mostly mild or moderate in intensity and resolved with continuous treatment; however, 5 patients (all male, 1 mg/kg dose) experienced 5 severe IRRs. These 5 IRRs were also 9 serious. Four of these events were confirmed type I hypersensitivity reactions and 3 led to the discontinuation from the study.
Another patient was later withdrawn from the study, after the occurrence of another moderate IRR. All 5 patients however recovered within the day after of occurrence with appropriate treatment. IRRs predominantly occurred within the first year of treatment with pegunigalsidase alfa and no serious IRR was observed during the second year and beyond.
4%) treated with 2 mg/kg pegunigalsidase alfa every four weeks developed treatment-induced anti-drug antibodies (ADAs). Membranoproliferative glomerulonephritis During the clinical development of pegunigalsidase alfa, one patient out of 141 reported a severe event of membranoproliferative glomerulonephritis after receiving treatment for more than 2 years.
The patient was ADA positive at the start of the infusions. The event led to a transitory reduction in the eGFR and an increase on the level of proteinuria, with no additional signs or symptoms. A biopsy revealed the immune-complex mediated nature of this event.
Upon discontinuation of the treatment, the eGFR values stabilised and the glomerulonephritis was reported as resolving. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.