Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Summary of safety profile

The most common adverse reactions (ADRs) associated with the administration of Spinraza were headache, vomiting and back pain.
The safety of Spinraza was assessed in clinical trials based on two Phase 3 clinical studies in infants (CS3B) and children (CS4) with SMA, together with one Phase 2 study in infants and children with SMA (CS7) and open-label studies including pre-symptomatic infants (CS5) genetically diagnosed with SMA and infants and children with SMA. Study CS11 enrolled infantile and later-onset patients including those who had completed studies CS3B, CS4 and CS12. Of the 352 patients who received Spinraza up to a maximum of 5 years, 271 patients received treatment for at least 1 year.

Tabulated list of adverse reactions

The safety assessment of Spinraza is based on data from patients from clinical trials and from post- marketing surveillance. The ADRs associated with Spinraza administration are summarised in Table 1.

The assessment of undesirable effects is based on the following frequency data: Very common ( ≥ 1/10)
Not known (cannot be estimated from the available data)

Table 1: Adverse reactions related to Spinraza administration

MedDRA System Organ Class                  Adverse reaction                      Frequency category 
Infections and infestations                Meningitis                            Not known Immune system disorders                    Hypersensitivity**                    Not known Nervous system disorders                   Headache*                             Very common Aseptic meningitis                    Not known
Gastrointestinal disorders                 Vomiting*                             Very common Musculoskeletal and connective             Back pain*                            Very common tissue disorders
*Adverse reactions considered related to the lumbar puncture procedure. These reactions can be considered manifestations of  post-lumbar puncture syndrome. These adverse reactions were reported in CS4 (later onset SMA) with an incidence at least 5% higher in patients treated with Spinraza (n=84) compared to Sham control.
**e.g. angiodema, urticaria and rash.

Events of communicating hydrocephalus have been observed in the post-marketing setting (see section 4.4).

Description of selected adverse reactions

Adverse reactions associated with the administration of Spinraza by lumbar puncture have been observed. The majority of these are reported within 72 hours of the procedure. The incidence and severity of these events were consistent with events expected to occur with lumbar puncture. No serious complications of lumbar puncture, such as serious infections, have been observed in the clinical trials of Spinraza.

Some adverse reactions commonly associated with lumbar puncture (e.g. headache and back pain) could not be assessed in the infant population exposed to Spinraza due to the limited communication appropriate for that age group.


Immunogenicity
The immunogenic response to nusinersen was determined in 346 patients with baseline and post-baseline plasma samples evaluated for anti-drug antibodies (ADA). Overall, the incidence of ADAs was low, with 15 (4%) patients classified as ADA positive overall, of which 4 had a transient response, 5 had a persistent response, and 6 patients had responses which could not be classified as transient or persistent at the time of data cut off. The impact of immunogenicity on safety was not formally analysed as the number of patients with ADAs was low. However, individual safety data for the treatment-emergent ADA-positive cases were reviewed, and no adverse events (AEs) of interest were identified.


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/