Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the clinical trials with ELELYSO, either as initial therapy or as therapy following a switch from imiglucerase (N=72), the most common ( ≥ 5%) adverse reactions included pruritus, flushing, headache, arthralgia, pain in extremity, abdominal pain, vomiting, fatigue, back pain, dizziness, nausea, and rash.
Clinical Trials of ELELYSO as Initial Therapy
Clinical Trial in Patients 19 Years and Older
The safety of ELELYSO at dosages of either 30 units/kg (n=16) or 60 units/kg (n=16) every other week was assessed in 32 adult treatment-naïve patients (aged 19 to 74 years) with Type 1 Gaucher disease in a 9-month randomized clinical trial.
Table 1: Adverse Reactions in ≥ 5% of Treatment-Naïve Adult Patients Treated with ELELYSO
|Preferred Term||Treatment-Naive Adults
|Abdominal pain||2 (6%)|
Similar adverse reactions were observed in patients who continued ELELYSO treatment during the extension trial for up to 24 months. One patient experienced a mild and intermittent Type III immune-mediated fixed drug eruption and continued in the study.
Clinical Trial in Patients 16 Years and Younger
The safety of ELELYSO at dosages of either 30 units/kg (n=4) or 60 units/kg (n=5) every other week was assessed in 9 pediatric treatment-naïve patients (aged 2 to 13 years) with Type 1 Gaucher disease in a 12month randomized clinical trial.
The most common adverse reaction ( ≥ 10%) was vomiting, which occurred in 4 of 9 patients. Two patients developed hypersensitivity reactions; one patient experienced severe vomiting and gastrointestinal inflammation, and 1 experienced mild throat irritation and chest discomfort. Both patients responded to treatment with antihistamines and continued ELELYSO treatment.
Clinical Trial in Patients Switching from Imiglucerase Treatment to ELELYSO
The safety of ELELYSO was assessed in 31 patients (26 adult and 5 pediatric patients), ages 6 to 66 years old, with Type 1 Gaucher disease who had previously been receiving treatment with imiglucerase for a minimum of 2 years. ELELYSO was administered for 9 months at the same number of units as each patient's previous imiglucerase dose.
Table 2: Adverse Reactions in ≥ 10% of Patients Switched from Imiglucerase to ELELYSO
|Preferred Term||Patients Switched from Imiglucerase
(N=31; 26 adults and 5 children)
|Pain in extremity||3 (10%)|
As with all therapeutic proteins, patients may develop anti-drug antibodies (ADA) to ELELYSO.
In clinical trials of treatment-naïve adults, 17 (53%) of 32 patients developed ADA during treatment with ELELYSO, and 2 (6%) of 32 patients tested positive for ADA at baseline prior to ELELYSO treatment. Of the 17 patients who developed ADA during ELELYSO treatment, 6 patients (35%) developed hypersensitivity reactions, 2 of whom met criteria for anaphylaxis. Two of the 17 patients who developed ADA during ELELYSO treatment discontinued treatment due to hypersensitivity reactions, one of whom had met criteria for anaphylaxis. Of the 2 patients who tested positive for ADA prior to initiation of ELELYSO treatment, one patient developed a hypersensitivity reaction during the first dose of ELELYSO and withdrew from the study. The second patient did not experience an adverse reaction.
In a clinical trial of treatment-naïve pediatric patients, 2 (22%) of 9 patients developed ADA during treatment with ELELYSO, and one of 9 patients was ADA-positive prior to initiation of ELELYSO. Two patients (1 who developed ADA during treatment and 1 who was ADA-positive at baseline) experienced hypersensitivity reactions. Both patients continued treatment with ELELYSO.
In a clinical trial of 31 patients (26 adult and 5 pediatric patients) who switched from imiglucerase to ELELYSO treatment, 4 adults (13% of patients) developed ADA during treatment with ELELYSO. Four additional patients (13%, 2 adults and 2 children) tested positive for ADA at baseline but became ADA-negative after the switch to ELELYSO. Two adult patients (1 patient who developed ADA after the switch and 1 who was ADA positive at baseline) experienced hypersensitivity reactions. Both patients continued treatment with ELELYSO.
The relationship between ADA and hypersensitivity reactions is not fully understood. Monitoring for ADA to ELELYSO may be useful in ADA positive patients or in patients who have experienced hypersensitivity reactions to ELELYSO or other enzyme replacement therapies.
Twenty-nine of the 30 adult and pediatric patients who tested positive for ADA were tested for neutralizing antibodies capable of inhibiting the enzymatic activity of ELELYSO. Neutralizing antibodies were detected in 3 (10.3%) of 29 patients, 2 treatment-naïve adult patients and 1 adult patient who switched from imiglucerase. Due to limited available data, it is not possible to determine a relationship between the presence of neutralizing antibodies and therapeutic response with ELELYSO.
Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to ELELYSO with the incidence of antibodies to other products may be misleading.
The following adverse reactions have been identified during post approval use of ELELYSO in countries where it is marketed. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders: Anaphylaxis [see WARNING AND PRECAUTIONS].