as described in the section below
Description of selected adverse reactions
Infusion-related reaction
IRRs (including hypersensitivity, nausea, vomiting, pyrexia, chills, feeling hot, malaise, urticaria,anaphylactoid reaction and hyperhidrosis) were reported in 9% of the patients (3 out of 33 patients) inclinical studies. All were mild or moderate in severity and none were reported as a serious adverseevent. All patients who experienced IRRs recovered.
Acute renal failureIn the clinical studies, one patient experienced acute renal failure considered possibly related to thestudy treatment. Acute renal failure was of moderate severity leading to temporary discontinuation ofthe study treatment and fully resolved within 3 months. Concomitant long-term treatment with highdoses of ibuprofen was noted as a potentially causative contributor to the occurrence of the event.
Loss of consciousness
In one patient, loss of consciousness considered related to the study treatment with recovery after afew seconds was reported. The patient received saline infusion in a hospital setting and was thendischarged after 6-hour observation.
The patient later experienced epileptic seizures that were considered not related.
Paediatric populationThe safety profile of velmanase alfa in clinical studies involving children and adolescents was similarto that observed in adult patients. Overall, 58% of patients (19 out of 33) with alpha-mannosidosisreceiving velmanase alfa in clinical studies were aged 6 to 17 years at the start of the study.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
4.9 Overdose
There is no experience with overdose of velmanase alfa. The maximum dose of velmanase alfa inclinical studies was a single administration of 100 units/kg (approximately corresponding to
3.2 mg/kg). During the infusion with this higher dose, fever of mild intensity and short duration(5 hours) was observed in one patient. No treatment was administered.
For the management of adverse reactions, see sections 4.4 and 4.8.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes.
ATC code: A16AB15.
Mechanism of actionVelmanase alfa, the active substance of Lamzede, is a recombinant form of human alpha-mannosidase.
The amino acid sequence of the monomeric protein is identical to the naturally occurring humanenzyme, alpha-mannosidase.
Velmanase alfa is intended to supplement or replace natural alpha-mannosidase, an enzyme thatcatalyses the sequential degradation of hybrid and complex high-mannose oligosaccharides in thelysosome, reducing the amount of accumulated mannose-rich oligosaccharides.
Clinical efficacy and safety
A total of 33 patients (20 males and 13 females, ranging in age from 6 to 35 years) were exposed tovelmanase alfa in five clinical studies. Patients were diagnosed based on alpha-mannosidase activity<10% of normal activity in blood leukocytes. Patients with the most severe rapidly progressingphenotype (with a deterioration within one year and central nervous system involvement) were
excluded. Based o |
