Adverse reactions : תופעות לוואי

6 ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5%) reported in clinical studies were vomiting, nausea, liver function test increased, pyrexia, and thrombocytopenia.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Acute serious liver injury [see Warnings and Precautions (5.1)]
• Immune-mediated myositis [see Warnings and Precautions (5.2)]
• Myocarditis [see Warnings and Precautions (5.3)]

6.1 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.

The safety data described in this section reflect exposure to a one-time intravenous infusion of ELEVIDYS in 85 male subjects with a confirmed mutation of the DMD gene in three on-going clinical studies, including two open-label studies and one study that included a double-blind, placebo-controlled period. Prior to ELEVIDYS infusion, patients in the ELEVIDYS treatment group had a mean age of 7.08 years (range: 3 to 20) and mean weight of 25.91 kg (range: 12.5 to 80.1). 73 subjects received the recommended dose of 1.33 × 1014 vg/kg, and 12 received a lower dose. Table 3 below presents adverse reactions from these three clinical studies.

The most common adverse reactions (incidence ≥5%) across all studies are summarized in Table 3.

Adverse reactions were typically seen within the first 2 weeks (nausea, vomiting, thrombocytopenia, pyrexia), or within the first 2 months (immune-mediated myositis, liver function test increased). Vomiting may occur as early as on the day of the infusion.

Table 3. Adverse reactions (Incidence ≥5%) following treatment with ELEVIDYS in Clinical Studies Adverse reactions                     ELEVIDYS
(N=85) %
Vomiting                                              61
Nausea                                                40
Liver function test increaseda                        37
Pyrexia                                               24 b
Thrombocytopenia                                      12
a
Includes: AST increased, ALT increased, GGT increased, GLDH increased, hepatic enzyme increased, transaminases increased, blood bilirubin increased b
Transient, mild, asymptomatic decrease in platelet counts

In the double-blind, placebo-controlled trial (Study 1 Part 1), subjects 4 to 7 years of age (N=41) received either ELEVIDYS (N=20) at the recommended dose of 1.33 × 1014 vg/kg (n=8) or lower dose (n=12) or received placebo (N=21). Table 4 below presents the most frequent adverse reactions from Study 1 Part 1.

Table 4. Adverse reactions occurring in ELEVIDYS-treated subjects and at least 10% more frequently than in placebo in Study 1, Part 1
Adverse reactions             ELEVIDYS        Placebo
(N=20) %      (N=21) %
Vomiting                                   65            33
Nausea                                     35            10
Liver function test increaseda             25             0
Pyrexia                                    20             5 a
Includes: AST increased, ALT increased, GGT increased, GLDH increased, hepatic enzyme increased, transaminases increased, blood bilirubin increased.

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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il