Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Summary of the safety profile

In infantile-onset SMA patients, the most common adverse reactions observed in Evrysdi clinical studies were pyrexia (54.8%), rash (29.0%) and diarrhoea (19.4%).

In later-onset SMA patients, the most common adverse reactions observed in Evrysdi clinical studies were pyrexia (21.7%), headache (20.0%), diarrhoea (16.7%), and rash (16.7%).

The adverse reactions listed above occurred without an identifiable clinical or time pattern and generally resolved despite ongoing treatment in infantile-onset and later-onset SMA patients.

Based on the primary analysis of RAINBOWFISH, the safety profile of Evrysdi in pre-symptomatic patients is consistent with the safety profile of symptomatic infantile-onset and later-onset SMA patients. The RAINBOWFISH study enrolled 26 patients with pre-symptomatic SMA between 16 and 41 days of age at the time of the first dose (weight range 3.1 to 5.7 kg). The median exposure duration


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was 20.4 months (range: 10.6 to 41.9 months). Limited post-marketing data are available in neonates <20 days of age.

See also section 5.3 for the effects of Evrysdi observed in nonclinical studies.

Tabulated list of adverse reactions
The corresponding frequency category for each adverse drug reaction is based on the following convention: 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). Adverse drug reactions from clinical studies (Table 2) are listed by MedDRA system organ class.

Table 2. Adverse drug reactions occurring in patients with infantile-onset and later-onset SMA based on Evrysdi clinical studies


System Organ Class
Infantile-onset SMA                        Later-onset SMA
(Type 1)                              (Type 2 and 3)
Gastrointestinal disorders
Diarrhoea                                  Very common                              Very common Nausea                                     Not applicable                             Common Mouth ulcerations and
Common                                    Common aphthous ulcers
Skin and subcutaneous tissue disorders
Rash*                           Very common                                         Very common Nervous system disorders
Headache                                   Not applicable                           Very common General disorders and administration site conditions

Pyrexia (including                         Very common                              Very common hyperpyrexia)
Infections and infestations
Urinary tract infection
Common                                    Common
(including cystitis)
Musculoskeletal and connective tissue disorders
Arthralgia                     Not applicable                                           Common *Includes dermatitis, dermatitis acneiform, dermatitis allergic, erythema, folliculitis, rash, rash erythematous, rash maculo-papular, rash papular

Safety profile in patients previously treated with other SMA-modifying therapies 
Based on the primary analysis of the JEWELFISH study, the safety profile of Evrysdi in SMA treatment non-naive patients who received Evrysdi for up to 59 months (including those previously treated with nusinersen [n=76] or with onasemnogene abeparvovec [n=14]) is consistent with the safety profile in SMA treatment-naive patients treated with Evrysdi in the FIREFISH, SUNFISH and RAINBOWFISH studies (see section 5.1).


Post-marketing experience


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Cutaneous vasculitis was reported during post-marketing experience. Symptoms recovered after permanent discontinuation of Evrysdi. The frequency cannot be estimated based on available data.

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/