Medicinal Products

ELAPRASE 2 mg / mL

Generic drug of the therapeutic class: Metabolism and nutrition
active ingredients: Idursulfase
laboratory: Shire HG Therapies Ltd

Solution for solution for IV infusion
Box of 1 bottle of 3 ml
All forms

Indication

Elaprase is indicated for the long-term treatment of patients with Hunter's syndrome (Mucopolysaccharidosis II, MPS II).

No clinical studies have been performed in heterozygous women.

Dosage ELAPRASE 2 mg / mL Concentrate for solution for infusion IV Box of 1 vial of 3 ml

Elaprase treatment should be supervised by a physician or other health professional experienced in the management of patients with MPS II or other inherited metabolic disease.

Dosage

Elaprase is administered at a dose of 0.5 mg / kg body weight each week by intravenous infusion for 3 hours, which can be progressively reduced to 1 hour if no infusion-related reaction is observed (see section 4.4). and precautions for use ).

Home-based infusion of Elaprase may be considered in patients who have received hospital treatment for several months and in whom good treatment tolerance has been observed. Home infusions will be performed under the supervision of a physician or other health professional.

Special populations

Elderly

There is no clinical experience in the subject over 65 years old.

Patients with renal or hepatic impairment

There is no clinical experience in patients with renal or hepatic impairment. See section Pharmacokinetic properties .

Pediatric population

The dose for children and adolescents is 0.5 mg / kg body weight per week.

Administration mode

For instructions on drug dilution before administration, see Instructions for Use, Handling and Disposal .

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under Composition .

Elaprase side effects

Summary of the security profile

Adverse events reported in 32 patients treated with 0.5 mg / kg of Elaprase weekly in the 52-week placebo-controlled Phase II / III TKT024 study were almost all of mild to moderate severity. The most common were infusion-related reactions: 202 were reported in 22 of 32 patients following administration of a total of 1, 580 infusions. In the placebo group, 128 infusion-related reactions were reported in 21 of 32 patients following administration of a total of 1612 infusions. Given that several infusion-related reactions may occur during a single infusion, the numbers mentioned above may overestimate the true incidence of infusion-related reactions. The infusion reactions that occurred in the placebo group were similar in nature and severity to those seen in the treated group. The most common infusion-related reactions included: skin reactions (rash, pruritus, urticaria), pyrexia, headache, and hypertension. The frequency of these infusion-associated reactions decreased over time with continued treatment.

Tabulated list of adverse effects

The adverse effects of the product are listed in the table below and presented by organ system class and frequency. The frequency is defined according to the following classification: very frequent (≥ 1/10) or frequent (≥ 1/100, <1/10). The occurrence of an adverse event in a single patient was considered a frequent event given the number of patients treated. Within each frequency group, adverse effects are presented in order of decreasing severity. Adverse reactions reported only during the post-marketing period are also presented in the following table, under the category "Frequency not known" (can not be estimated from the available data).

Class of organ system

Adverse effect of treatment (Preferred term)

Very common

Frequent

Undetermined

Immune system disorders

Anaphylactoid reaction

Nervous system disorders

headaches

Dizziness, tremors

Heart conditions

Cyanosis, arrhythmia, tachycardia

Vascular disorders

Hypertension, flushing

hypotension

Respiratory, thoracic and mediastinal disorders

Sibilance, dyspnoea

Hypoxia, tachypnea, bronchospasm, cough,

Gastrointestinal disorders

Abdominal pain, nausea, dyspepsia, diarrhea, vomiting

Swollen tongue

Skin and subcutaneous tissue disorders

Urticaria, rash, pruritus

Erythema,

Musculoskeletal and systemic disorders

arthralgia

General disorders and administration site conditions

Fever, chest pain, swelling at the infusion site

Edema of the face, peripheral edema

Injury, poisoning and procedural complications

Reaction in relation to perfusion

Description of some adverse effects

In the various studies, serious adverse events were reported in a total of 5 patients who received 0.5 mg / kg weekly or every 15 days. Four patients experienced a hypoxic episode during one or more infusions, requiring oxygen therapy in 3 patients with severe underlying obstructive bronchopneumopathy (2 with pre-existing tracheostomy). The most severe episode occurred during infusion in a patient with febrile respiratory distress syndrome with hypoxia and resulted in a short-term seizure. In the fourth patient, with a less severe underlying condition, spontaneous resolution was observed shortly after stopping the infusion. These events did not recur during the following infusions due to the implementation of a slower infusion rate and pretreatment prior to infusion (generally, low dose steroids, antihistamines and nebulized beta-agonists). ). In the fifth patient with pre-existing cardiac disease, ventricular extrasystoles and pulmonary embolism were diagnosed during the study.

Anaphylactoid reactions associated with Elaprase have been reported after marketing. For more information, see the Warnings and Precautions section .

Patients with a complete deletion / genotype rearrangement are more likely to have infusion-related adverse events (see Warnings and Precautions section ).

immunogenicity

In 4 clinical studies (TKT008, TKT018, TKT024 and TKT024EXT), 53/107 patients (50%) developed anti-idursulfase IgG antibodies at some point. The overall rate of neutralizing antibodies was 26/107 patients (24%).

A post-hoc analysis evaluating the immunogenicity data from the TKT024 / 024EXT studies showed that 51% (32/63) of the patients treated with a weekly dose of Elaprase of 0.5 mg / kg had a positive antibody result. anti-Elaprase on at least one blood sample and 37% (23/63) continued to show anti-drug antibodies for at least 3 consecutive study visits. Twenty-one percent (13/63) of patients had at least one neutralizing antibody positive result and 13% (8/63) continued to show neutralizing antibodies for at least 3 consecutive study visits.

Clinical study HGT-ELA-038 evaluated the immunogenicity profile of the product in children aged 16 months to 7.5 years. In this 53-week study, 67.9% of patients (19 of 28) tested positive for anti-Elaprase antibodies in at least one sample and 57.1% (16 of 28) tested positive for antibodies. during at least three consecutive visits. Fifty-four percent of the patients tested positive for neutralizing antibodies on at least one sample and half were tested positive for neutralizing antibodies in at least three consecutive visits.

Patients with a complete deletion / rearrangement genotype all developed antibodies and the majority of them (7/8) tested positive for neutralizing antibodies on at least 3 consecutive assays. Patients whose genotype had a reading frame shift / splice site mutation all developed antibodies, and 4 out of 6 patients were also tested positive for neutralizing antibodies in at least 3 consecutive visits . Patients tested negative for antibodies belonged exclusively to the group whose genotype contained a missense mutation (see sections Warnings and precautions for use and Pharmacodynamic properties ).

Pediatric population

The adverse effects observed in the pediatric population were generally similar to those reported in adults.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.

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