Lamzede

The treatment should be supervised by a physician experienced in the management of patients with alpha-mannosidosis or in the administration of other enzyme replacement therapies (ERT) for lysosomal storage disorder. Administration of Lamzede should be carried out by a healthcare professional with the ability to manage ERT and medical emergencies.

Posology The recommended dose regimen is 1 mg/kg of body weight administered once every week by intravenous infusion at a controlled speed. The effects of treatment with velmanase alfa should be periodically evaluated and discontinuation of treatment considered in cases where no clear benefits could be observed.

Special populations Elderly No data are available and no relevant use in elderly patients is described. Renal or hepatic impairment No dose adjustment is necessary for patients with renal or hepatic impairment. 3 Paediatric population No dose adjustment is necessary for the paediatric population.

Method of administration For intravenous infusion use only. Instructions on reconstitution of the medicinal product before administration The reconstituted solution should be clear. 6). 22 μm filter. The infusion duration should be calculated individually considering a maximum infusion rate of 25 mL/hour to control the protein load.

The infusion duration should be a minimum of 50 minutes. A slower infusion rate may be prescribed when clinically appropriate according to the physician’s judgment, for example at the beginning of the treatment or in case of previous infusion-related reactions (IRRs).

6. The patient should be observed for IRRs for at least one hour after the infusion according to clinical conditions and the physician’s judgment. For further instructions, see section

Summary of the safety profile The most common adverse reactions observed were weight increase (15%), IRRs (13%), diarrhoea (10%), headache (7%), arthralgia (7%), increased appetite (5%) and pain in extremity (5%). The majority of these adverse reactions were non-serious.

IRRs include hypersensitivity in 3 patients and anaphylactoid reaction in 1 patient. These reactions were mild to moderate in intensity. A total of 4 serious adverse reactions (loss of consciousness in 1 patient, acute renal failure in 1 patient, chills and hyperthermia in 1 patient) were observed.

In all cases the patients recovered without sequelae. Tabulated list of adverse reactions The adverse reactions reflecting exposure of 38 patients treated with velmanase alfa in clinical studies are listed in the table 1 below. Adverse reactions are classified by system organ class and preferred term according to the MedDRA frequency convention.

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Frequency is 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) or not known (cannot be estimated from the available data).

6 Table 1: Adverse reactions reported from clinical studies, post-authorization safety studies and spontaneous reporting in patients with alpha-mannosidosis treated with velmanase alfa System organ class Adverse reaction Frequency Infections and infestations Bacterial disease carrier Not known Endocarditis Not known Furuncle Not known Staphylococcal infection Not known Immune system disorders Hypersensitivity(1) Common Anaphylactoid reaction(1) Common Metabolism and nutrition disorders Increased appetite Common Decreased appetite Not known Psychiatric disorders Psychotic behaviour Common Initial insomnia Common Agitation Not known Encopresis Not known Psychotic disorder Not known Nervousness Not known Apathy(1) Not known Nervous system disorders Loss of consciousness(2) Common Tremor Common Confusional state Common Syncope Common Headache Common Dizziness Common Ataxia Not known Nervous system disorder Not known Somnolence Not known Hypotonia(1) Not known Eye disorders Eyelid oedema Common Eye irritation Common Ocular hyperaemia Common Lacrimation increased Not known Ear and labyrinth disorders Deafness Not known Cardiac disorders Cyanosis(1) Common Bradycardia Common Aortic valve incompetence Not known Palpitations Not known Tachycardia Not known Vascular disorders Hypotension Not known Vascular fragility Not known Pallor(1) Not known Respiratory, thoracic and mediastinal disorders Epistaxis Common Oropharyngeal pain Not known Pharyngeal oedema Not known Wheezing Not known Gastrointestinal disorders Diarrhoea Very common Vomiting(1) Common Abdominal pain upper Common Nausea(1) Common Abdominal pain Common Reflux gastritis Common Odynophagia Not known 7 System organ class Adverse reaction Frequency Skin and subcutaneous tissue disorders Urticaria(1) Common Hyperhidrosis(1) Common Angioedema Not known Erythema Not known Rash Not known Musculoskeletal and connective tissue disorders Arthralgia Common Pain in extremity Common Joint stiffness Common Myalgia Common Back pain Common Joint swelling Not known Joint warmth Not known Renal and urinary disorders Renal failure acute(2) Common General disorder and administration site conditions Pyrexia(1) Very common Chills(1) Common Catheter site pain Common Feeling hot(1) Common Fatigue Common Malaise(1) Common Asthenia Not known Investigations Weight increase Very common Injury, poisoning and procedural complications Procedural headache Common Infusion related reaction Not known (1) Preferred terms considered as IRR as described in the section below (2) Selected adverse reaction as described in the section below Description of selected adverse reactions Infusion-related reaction IRRs (including hypersensitivity, cyanosis, nausea, vomiting, pyrexia, chills, feeling hot, malaise, urticaria, anaphylactoid reaction and hyperhidrosis) were reported in 13% of the patients (5 out of 38 patients) in clinical studies.

4. Home infusion Infusion of Lamzede at home may be considered for patients who are tolerating their infusions well. The decision to have a patient move to home infusion should be made after evaluation and recommendation by the treating physician.

Patients experiencing infusion-related reactions, including hypersensitivity reactions or anaphylactic reactions, during the home infusion need to immediately reduce the infusion rate or to stop the infusion process considering the severity of the reaction and seek the attention of a healthcare professional.

Dose and infusion rate in home setting should remain the same used in the hospital setting; they could be changed only under the supervision of a healthcare professional and treating physician. Appropriate training should be given by the treating physician and/or nurse to the patient and/or caregiver prior to initiation of home infusion.

1. 4 Special warnings and precautions for use 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. General consideration on the treatment As the accumulation of end organ damage progresses over time, it is more difficult for the treatment to reverse the damage or to show improvements.

As with other enzyme replacement therapies, velmanase alfa does not cross the blood-brain-barrier. e. skeletal deformities, disostosis multiplex, neurological manifestations and impaired cognitive function). 4 Hypersensitivity Hypersensitivity reactions have been reported in patients in clinical studies.

Appropriate medical support should be readily available when velmanase alfa is administered. If severe allergic or anaphylactic-type reactions occur, immediate discontinuation of velmanase alfa is recommended and current medical standards for emergency treatment are to be followed.

1.