Adverse reactions : תופעות לוואי

4.8    Undesirable effects

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 randomized, 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 (≥ 1/1000 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
MedDRA                           MedDRA                            Frequency System organ class               Preferred term
Immune system disorders          Anaphylaxis                       Uncommon Hypersensitivity                  Common
Nervous system disorders         Headache                          Very common Dizziness                         Very common
Respiratory, thoracic, and       Dyspnoea                          Very common mediastinal disorders
Gastrointestinal disorders       Diarrhoea, vomiting,              Very common oropharyngeal pain, upper abdominal pain, abdominal pain,
nausea
Musculoskeletal and connective Myalgia                             Common tissue disorders                 Chills                            Very common General disorders and            Pyrexia                           Very common administration site conditions
Description of selected adverse reactions

Immunogenicity

All patients developed antibodies to elosulfase alfa in clinical trials. 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 trials, 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
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.he alth.gov.il ) or by email (adr@MOH.HEALTH.GOV.IL ).