FDA approves Roche’s Evrysdi (risdiplam) for treatment of spinal muscular atrophy (SMA) in adults and children 2 months and older

In two clinical trials, Evrysdi improved motor function in people living with SMA over a broad spectrum of ages and levels of disease severity, including Types 1, 2, and 3 SMAEvrysdi helped infants survive without permanent ventilation and achieve the ability to sit without support, a key motor milestone not normally seen in the natural course of the diseaseEvrysdi is the first and only medicine for SMA that can be taken at home             
Basel, 10 August 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) Roche announced today that the U.S. Food and Drug Administration (FDA) has approved Evrysdi™ (risdiplam) for the treatment of spinal muscular atrophy (SMA) in adults and children 2 months of age and older. 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.41% (7/17) of infants treated with the therapeutic dose achieved the ability to sit without support for at least 5 seconds as measured by the BSID-III gross motor scale.90% (19/21) of all infants were alive without permanent ventilation* and reached 15 months of age or older81% (17/21) of all patients were alive without permanent ventilation* after a minimum of 23 months of treatment and reached an age of 28 months or older (median 32 months; range 28 to 45 months) * Permanent ventilation defined as tracheostomy or ≥16 hours of noninvasive ventilation per day or intubation for ≥21 consecutive days in the absence of, or following the resolution of, an acute reversible event.

SUNFISH (NCT02908685)
SUNFISH, a two-part placebo-controlled multicenter pivotal trial, was designed to assess Evrysdi safety, tolerability, efficacy, PK and PD in people with Type 2 or 3 SMA aged 2 to 25, including those with scoliosis (67% in Part 2) and joint contractures at baseline. In Part 2, after 12 months, Evrysdi treatment led to:A clinically-meaningful and statistically significant improvement in motor function among children and adults, as measured by a change from baseline in the MFM-32 total score (1.55 point mean difference; p=0.0156), at 12 months as compared to placebo (1.36 points [95% CI: 0.61, 2.11]; -0.19 points [95% CI: 1.22, 0.84], respectively). MFM-32 assesses 32 different motor functions across a wide range of people with SMA.Improved upper limb motor function compared to baseline, as measured by the Revised Upper Limb Module (RULM), a secondary independent motor function endpoint of the study (1.59 point difference; p=0.0028).
Pivotal Trial Safety Data
The safety profile of Evrysdi was established across the FIREFISH and SUNFISH pivotal trials. The most common adverse reactions in later-onset SMA (incidence of at least 10% of patients treated with Evrysdi and more frequently than control) were fever, diarrhea, and rash. The most common adverse reactions in infantile-onset SMA were similar to those observed in later-onset SMA patients. Additionally, the most common adverse reactions (incidence of at least 10%) were upper respiratory tract infection, pneumonia, constipation, and vomiting.

About the Evrysdi Clinical Trial Program
In addition to FIREFISH and SUNFISH, Evrysdi is being evaluated in a broad range of people with SMA, including in:JEWELFISH (NCT03032172): an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. Recruitment for this study is complete with 174 people enrolled.RAINBOWFISH (NCT03779334): an open-label, single-arm, multicenter study investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Evrysdi in infants (~n=25), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.
About SMA
SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.
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