Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The most common adverse reaction reported was injection site reaction (35%).
Tabulated list of adverse reactions

Adverse reactions associated with lumasiran obtained from clinical studies are tabulated below. The adverse reactions are coded to preferred terms (PTs) under the MedDRA system organ class (SOC) and are presented by frequency. The frequency of the adverse reactions is expressed according to the following categories: 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).

Table 2: Adverse reactions
System organ class                             Adverse reaction                    Frequency a
Gastrointestinal disorders                              Abdominal pain                   Very common General disorders and administration                  Injection site reactionb              Very common site conditions a
Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and abdominal tenderness.
b
Includes injection site reaction, injection site erythema, injection site pain, injection site pruritus, injection site swelling, injection site discomfort, injection site discolouration, injection site mass, injection site induration, injection site rash, injection site bruising, injection site haematoma and injection site exfoliation.

Description of selected adverse reactions

Injection site reactions
In placebo-controlled and open-label clinical studies, injection site reactions were reported in 34 out of 98 patients (34.7%). The most commonly reported symptoms were erythema, swelling, pain, haematoma, pruritus, and discolouration.. The majority of injection site reactions started on the day of administration, with<2% of injection site reactions occurring 5 or more days after administration.
Injection site reactions were generally mild, resolved within two days, and did not result in interruption or discontinuation of treatment.

Abdominal pain
In the placebo-controlled study, abdominal pain was reported in 1 of 13 (7.7%) placebo-treated patients and 4 of 26 (15.4%) lumasiran-treated patients. In the placebo-controlled and open-label clinical studies, 16 of 98 patients (16.3%) reported abdominal pain, including upper or lower abdominal pain, abdominal discomfort, or abdominal tenderness. Most of the events have been mild, transient and resolved without treatment. None have resulted in discontinuation of treatment.


Immunogenicity
In patients with PH1 and healthy volunteers dosed with Oxlumo, in clinical studies, 7 of 120 (5.8%) individuals tested positive for anti-drug-antibodies (ADA). ADA titres were low and generally transient, with no impact on the efficacy, safety, pharmacokinetic, or pharmacodynamic profiles of the medicinal product.

Paediatric population

The safety profile of lumasiran was similar in paediatric (aged 4 months to 17 years) and adult patients with PH1.

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/