EVRYSDI

What it is

Evrysdi is risdiplam, available as a powder for oral solution and film-coated tablet. The powder for oral solution is supplied as 60 mg per bottle. The film-coated tablet contains 5 mg of risdiplam. This medicinal product is subject to additional monitoring in Australia to allow quick identification of new safety information. Evrysdi is a survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier designed to treat spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that lead to SMN protein deficiency. It corrects the splicing of SMN2 to shift the balance from exon 7 exclusion to exon 7 inclusion into the mRNA transcript, leading to increased production of functional and stable SMN protein, thereby treating SMA by increasing and sustaining functional SMN protein levels. Risdiplam distributes evenly to all parts of the body, including the central nervous system by crossing the blood brain barrier.

Approved indications

— Treatment of 5q spinal muscular atrophy (SMA).

Dosing overview

The recommended once daily dose of Evrysdi for SMA patients is determined by age and body weight. For infants younger than 2 months of age, the dose is 0.15 mg/kg. For patients aged 2 months to less than 2 years, the dose is 0.20 mg/kg. For patients aged 2 years and older weighing less than 20 kg, the dose is 0.25 mg/kg. For patients aged 2 years and older weighing 20 kg or more, the dose is 5 mg. Evrysdi is taken once daily with or without food at approximately the same time each day. Treatment should be initiated as early as possible after diagnosis and initiated and monitored by a specialist medical practitioner experienced in the diagnosis and management of SMA.

Key safety warnings

Embryo-fetal toxicity has been observed in animal studies. Patients of reproductive potential should be informed of the risks and must use highly effective contraception during treatment and until at least 1 month after the last dose of Evrysdi in female patients, and 4 months after the last dose in male patients. Male patients should not donate sperm while on treatment and for 4 months after the last dose of Evrysdi due to reversible effects on male fertility based on observations from animal studies. Prior to initiating treatment, fertility preservation strategies should be discussed with male patients. Male patients may consider sperm preservation prior to treatment initiation or after a treatment-free period of at least 4 months. Male patients who wish to father a child should stop treatment with Evrysdi for a minimum of 4 months. Effects on retinal structure observed in non-clinical safety studies have not been observed in clinical studies with SMA patients. However, long-term data are still limited, and the clinical relevance of these nonclinical findings in the long-term has therefore not been established. The potential for synergistic effects of concomitant administration with retinotoxic drugs has not been studied. Caution in using concomitant medications with known or suspected retinal toxicity is recommended. Patients most likely to develop type 0 or IV SMA have not been included in the clinical development program. The decision to treat should be based on individualised expert evaluation of the expected benefits balanced against potential risk. The full benefits and risks are unknown among patients diagnosed with type 0 or IV SMA.

Contraindications

Evrysdi is contraindicated in patients with a known hypersensitivity to risdiplam or to any of the excipients.

PBS listing

The tablet 5 mg is listed on the PBS with 14 items, authority required restriction, at an ex-manufacturer price of A$25,297.74. The powder for oral solution 750 micrograms per mL, 80 mL is listed on the PBS with 20 items, authority required restriction, at an ex-manufacturer price of A$10,841.89.

Regulatory history

Evrysdi powder for oral solution 0.75 mg/mL was first registered on the ARTG on 2 June 2021. The film-coated tablet 5 mg was first listed on the ARTG on 29 September 2025. In March 2021, the PBAC recommended Evrysdi for spinal muscular atrophy in patients with SMA Types 1, 2 or 3a who are aged 18 years or under at treatment initiation. In March 2023, the PBAC recommended it for adults with 5q SMA and for pre-symptomatic patients aged less than 36 months with SMA1 deletion or mutation and SMN2 gene copy number of 1 or 2. In July 2024, the PBAC recommended Evrysdi for pre-symptomatic treatment initiation in patients aged less than 36 months, genetically diagnosed with SMA, who have a SMN2 gene copy number of 3.