VIMIZIM Concentrate for solution for infusion Ref.[114824] Active ingredients: Elosulfase alfa

Anaphylaxis and severe allergic reactions

Anaphylaxis and severe allergic reactions have been reported in clinical studies. Therefore, appropriate medical support must be readily available when elosulfase alfa is administered. If these reactions occur, immediately stop the infusion and initiate appropriate medical treatment. The current medical standards for emergency treatment are to be followed. For patients who have experienced allergic reactions during infusion, caution should be exercised upon re-administration.

Infusion reactions

Infusion reactions (IRs) were the most commonly observed adverse reactions in clinical studies. IRs may include allergic reactions. Patients should receive antihistamines with or without antipyretics prior to infusion (see section 4.2). Management of IRs should be based on the severity of the reaction and include slowing or temporary interruption of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids. If severe IRs occur, immediately stop the infusion and initiate appropriate treatment. Re-administration after a severe reaction should be carried out with caution and close monitoring by the treating physician.

Spinal/Cervical cord compression

In clinical studies, spinal/cervical cord compression (SCC) was observed both in patients receiving Vimizim and patients receiving placebo. Patients should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, urinary and faecal incontinence) and given appropriate clinical care.

Sodium restricted diet

This medicinal product contains 8 mg sodium per vial, equivalent to 0.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult, and is administered in sodium chloride 9 mg/ml (0.9%) solution for infusion (see section 6.6).

Sorbitol (E420)

This medicinal product contains 100 mg sorbitol in each vial which is equivalent to 40 mg/kg. Patients with hereditary fructose intolerance (HFI) must not be given this medicinal product unless strictly necessary.

Babies and young children (below 2 years of age) may not yet be diagnosed with hereditary fructose intolerance (HFI). Medicinal products containing sorbitol/fructose given intravenously may be life-threatening. The treatment benefit to the child compared to the associated risks must be fully evaluated prior to treatment.

A detailed history with regard to HFI symptoms has to be taken for each patient prior to being given this medicinal product.

No interaction studies have been performed.

Pregnancy

There are no data on the use of Vimizim in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryo-foetal development (see section 5.3). These studies however, are of limited relevance. As a precautionary measure, it is preferable to avoid the use of Vimizim during pregnancy, unless clearly necessary.

Breast-feeding

Available reproductive data in animals have shown excretion of elosulfase alfa in milk. It is not known whether elosulfase alfa is excreted in human breast milk, but systemic exposure via breast milk is not expected. Due to lack of human data, Vimizim should only be administered to breast-feeding woman if the potential benefit is considered to outweigh the potential risk to the infant.

Fertility

No impairment of fertility has been observed in nonclinical studies (see section 5.3) with elosulfase alfa.

Vimizim has minor influence on the ability to drive and use machines. Dizziness was reported during Vimizim infusions; if dizziness occurs after the infusion, the ability to drive and use machines may be affected.

Summary of the safety profile

The assessment of adverse reactions is based on the exposure of 176 patients with MPS IVA, ages 5 to 57 years old to 2 mg/kg elosulfase alfa once a week (n=58), 2 mg/kg elosulfase alfa once every other week (n=59), or placebo (n=59) in a randomised, double-blind, placebo-controlled study.

The majority of adverse reactions in clinical studies were IRs, which are defined as reactions occurring after initiation of infusion until the end of the day following the infusion. Serious IRs were observed in clinical studies and included anaphylaxis, hypersensitivity and vomiting. The most common symptoms of IRs (occurring in ≥10% of patients treated with Vimizim and ≥5% more when compared to placebo) were headache, nausea, vomiting, pyrexia, chills and abdominal pain. IRs were generally mild or moderate, and the frequency was higher during the first 12 weeks of treatment and tended to occur less frequently with time.

Tabulated list of adverse reactions

The data in Table 2 below describes adverse reactions from clinical studies in patients treated with Vimizim.

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

Table 2. Adverse reactions in patients treated with Vimizim:

Description of selected adverse reactions

Immunogenicity

All patients developed antibodies to elosulfase alfa in clinical studies. Approximately 80% of patients developed neutralizing antibodies capable of inhibiting the elosulfase alfa from binding to the cation- independent mannose-6-phosphate receptor. Sustained improvements in efficacy measures and reductions in urine keratan sulphate (KS) over time were observed across studies, despite the presence of anti elosulfase alfa antibodies. No correlations were found between higher antibody titres or neutralizing antibody positivity and reductions in efficacy measurements or occurrence of anaphylaxis or other hypersensitivity reactions. IgE antibodies against elosulfase alfa were detected in ≤10% of treated patients and have not consistently been related to anaphylaxis or other hypersensitivity reactions and/or treatment withdrawal.

Paediatric population

In patients <5 years of age, the overall safety profile of Vimizim at 2 mg/kg/week was consistent with the safety profile of Vimizim observed in older children.

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.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.