Summary of safety profile The assessment of adverse reactions was based on the exposure of 23 patients from 4 clinical trials, aged 5 months to 25 years, who received vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 187 weeks.
Nineteen patients were younger than 18 years of age. 7%). Most adverse reactions were mild to moderate in severity. 3%); the patient recovered without sequelae. Tabulated list of adverse reactions Table 1 lists the adverse reactions reported from 4 clinical trials in 23 patients treated with Mepsevii.
Adverse reactions are presented by System Organ Class and frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare ( ≥ 1/10,000 to < 1/1,000), and very rare (< 1/10,000).
Table 1 Adverse reactions reported in patients treated with Mepsevii MedDRA System Organ Class MedDRA Preferred Term (PT) Frequency Immune system disorders Anaphylactoid reaction Very common Nervous system disorders Febrile convulsion* Common Gastrointestinal disorders Diarrhoea Common Skin and subcutaneous tissue disorders Urticaria Rash** Pruritus Very common Very common Common General disorders and administration site conditions Infusion site extravasation*** Infusion site swelling**** Very common Common *Refer to description of selected adverse reactions for details on the febrile convulsion reported in 1 of 23 trial patients.
** Rash includes grouped PTs of rash, rash papular, rash pruritic, rash maculo- papular, papule, and macule *** Infusion site extravasation includes one PT of extravasation **** One adverse reaction of Peripheral swelling is included within the frequency of Infusion site swelling as the event is classified as intravenous catheter issue.
Description of selected adverse reactions Febrile Convulsion One patient receiving a vestronidase alfa dose of 4 mg/kg experienced a febrile convulsion during treatment at the week 66, within 3 days of diphtheria, tetanus, pertussis vaccination.
The infusion was stopped, the patient received anticonvulsants, antipyretics and antibiotics, and the febrile convulsion resolved. The patient subsequently was re-challenged without recurrence and continued on vestronidase alfa treatment.
This event was assessed as possibly related to vestronidase alfa due to the temporal association with the infusion. Immunogenicity Eighteen out of 23 patients (78%) from 4 clinical trials developed anti-recombinant human beta-glucuronidase (rhGUS) antibodies (ADA), ten of whom further developed neutralizing antibodies (NAb) on at least one occasion, but not consistently over time.
There is no definitive correlation between the antibody titre and neutralizing antibody development. In most patients, a pattern of attenuated immunogenicity with chronic exposure was suggested by declining antibody titres over time on continuous treatment.
The presence of ADA (non-NAb and NAb) does not appear to affect reduction in the pharmacodynamic marker, urinary glycosaminoglycans (uGAGs) and development of hypersensitivity reactions including infusion associated reactions. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.