Roche announced that the US Food and Drug Administration (FDA) has approved Evrysdi (risdiplam) for the treatment of spinal muscular atrophy (SMA) in adults and children two months of age and older. The company informed that Evrysdi showed clinically meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA. Infants achieved the ability to sit without support for at least 5 seconds, a key motor milestone not normally seen in the natural course of the disease. Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history. A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

“Given the majority of people with SMA in the US remain untreated, we believe Evrysdi, with its favourable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development.

Evrysdi is being studied in more than 450 people as part of a large and robust clinical trial program in SMA. The program includes infants aged two months to adults aged 60 with varying symptoms and motor function, such as people with scoliosis or joint contractures, and those previously treated for SMA with another medication. The approval is based on data from two clinical studies designed to represent a broad spectrum of people living with SMA: FIREFISH in symptomatic infants aged 2 to 7 months; and SUNFISH in children and adults aged 2 to 25 years. SUNFISH is the first and only placebo-controlled trial to include adults with Types 2 and 3 SMA.

In FIREFISH, 41 per cent (7/17) of infants treated with the therapeutic dose achieved the ability to sit without support for at least five seconds as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Additionally, 90 per cent (19/21) of infants were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older. As described in the natural history of untreated infantile-onset SMA, infants would not be expected to be able to sit independently, and only 25 per cent would be expected to survive without permanent ventilation beyond 14 months of age. In SUNFISH, children and adults treated with Evrysdi experienced a clinically-meaningful and statistically significant improvement in motor function at 12 months (1.55 point mean difference; p=0.0156) compared to placebo (1.36 points [95% CI: 0.61, 2.11]; -0.19 points [95% CI: -1.22, 0.84], respectively), as measured by a change from baseline in the Motor Function Measure-32 (MFM-32) total score.

Evrysdi demonstrated a favourable efficacy and safety profile, with the safety profile established across the FIREFISH and SUNFISH trials. The most common adverse reactions were fever, diarrhoea, and rash in later-onset SMA. In infantile-onset SMA, the most common adverse events were similar and also included upper respiratory tract infection, pneumonia, constipation, and vomiting. There were no treatment-related safety findings leading to withdrawal from either study.

Evrysdi is designed to treat SMA by increasing production of the survival of motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.