Two-year data from part two of FIREFISH, a Phase II/III global study by Roche evaluating Evrysdi (risdiplam) in infants aged 1-7 months at enrolment with symptomatic type one spinal muscular atrophy (SMA), showed that Evrysdi continued to improve motor function between months 12 and 24, including the ability to sit without support. The results also showed Evrysdi continued to improve survival and the ability to feed orally, and reduced the need for permanent ventilation, with an established safety profile.

The primary endpoint of the study evaluated the percentage of infants able to sit without support for at least five seconds at month 12. Results showed that at 12 months, infants treated with Evrysdi demonstrated improved ability to sit without support for at least five seconds and at least 30 seconds. In the 24-month data, results showed improvements from month 12, with 61% able to sit without support for at least five seconds and 44% able to sit without support for at least 30 seconds, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III).

Infants treated with Evrysdi maintained the ability to feed orally (92%) at month 24; infants with type one SMA older than 12 months generally require feeding support.

Around 93% of infants were alive after 24 months of treatment, with 83% free from permanent ventilation. The most common adverse events were upper respiratory tract infection (54%), pneumonia (46%), pyrexia (44%), constipation (29%), nasopharyngitis (17%), bronchitis (15%), diarrhea (15%) and rhinitis (12%).

Evrysdi aims to modulate the splicing mechanism of messenger ribonucleic acid (mRNA) to increase the production of functional survival motor neuron (SMN) proteins. Its mechanism is similar to Biogen ’s Spinraza (nusinersen), the first drug approved for SMA. The major difference is that Evrysdi is administered orally, rather than as an intrathecal injection. Oral administration minimises the use of institutional resources, enables SMA patients with scoliosis to be prescribed such drugs without the risk posed by a lumbar puncture, and is expected to increase the levels of functional SMN proteins in peripheral tissues as well as in the central nervous system.

Evrysdi was approved by the US Food and Drug Administration (FDA) last July and received a recommendation from the European Medicines Agency (EMA) in March. It was, however, expected to face challenges eroding Spinraza’s SMA market share, despite its convenient oral dosing, because of safety concerns and lack of long-term data. These positive long-term data, particularly in the context of the Covid-19 pandemic, give Evrysdi a significant competitive advantage. Evrysdi’s non-invasive oral treatment can provide a convenient at-home treatment and is seen as a strong contender in the SMA market.