Chugai Pharmaceutical's Evrysdi (risdiplam) has received approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) for an expanded indication to include pre-symptomatic spinal muscular atrophy (SMA) and for use in infants under two months of age. This approval marks a significant advancement in the treatment landscape for SMA, allowing for earlier intervention and potentially improved outcomes for affected individuals.
The approval is based on data from the Phase II RAINBOWFISH study (NCT03779334), an open-label, single-arm, multicenter trial that evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of Evrysdi in infants (up to 6 weeks of age at first dose) with genetically diagnosed SMA who had not yet developed symptoms. The study included infants with two or more copies of the SMN2 gene, with lower copy numbers generally correlating with more severe disease.
RAINBOWFISH Study Details
The RAINBOWFISH study's primary endpoint was the proportion of infants who could sit without support for at least 5 seconds at 12 months, as assessed by the Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) gross motor scale. While specific data from the RAINBOWFISH study were not detailed in the announcement, the approval indicates that the results were compelling enough to warrant the expanded indication.
Clinical Significance
"We are very pleased that with this approval, we can now deliver Evrysdi to people with SMA of all ages after birth, regardless of symptom onset," said Chugai’s President and CEO, Dr. Osamu Okuda. He emphasized the importance of early intervention in SMA treatment, stating, "SMA treatment is expected to maximize its effect when intervention begins at an earlier stage. We are confident that this approval will allow Evrysdi to contribute even more to SMA treatment."
In SMA, motor neuron loss can begin before symptoms manifest, making early treatment crucial for better outcomes. Newborn screening plays a vital role in early diagnosis, and Evrysdi's availability allows for immediate treatment initiation upon diagnosis, irrespective of symptom onset.
Evrysdi: Mechanism of Action and Availability
Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in the 5q chromosome, leading to SMN protein deficiency. It works by increasing and sustaining the production of the SMN protein, which is essential for maintaining healthy motor neurons and movement. Evrysdi is administered orally once daily after a meal.
The approved dosage for patients less than 2 months of age is 0.15 mg/kg risdiplam. For patients 2 months to less than 2 years, the dosage is 0.2 mg/kg. For those older than 2 years, the dosage is 0.25 mg/kg for patients weighing less than 20 kg and 5 mg for those weighing 20 kg or more.
Future Developments
Chugai has also submitted an application for a tablet formulation of Evrysdi for patients 2 years and older weighing 20 kg or more. If approved, the tablet formulation would offer more convenient storage and administration, potentially improving treatment adherence and quality of life for patients and caregivers.
