Risdiplam improves motor function and milestones in infants: Lancet

A new study published in The Lancet Neurology suggests that over the course of a 24-month treatment with risdiplam, motor function and developmental motor milestones were consistently improved.

Risdiplam is an oral medication that treats spinal muscular atrophy by altering the pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene. In contrast to historical controls, the FIREFISH research compares the safety and effectiveness of risdiplam in treating babies with type 1 spinal muscular atrophy. After receiving therapy for 12 months, babies with type 1 spinal muscular atrophy were able to sit alone for at least 5 seconds, according to the study's primary outcome. Here, Riccardo Masson and team discuss the safety and effectiveness of risdiplam across a 24-month therapy period in FIREFISH part 2.

An ongoing, multicenter, open-label, two-part study is called FIREFISH. Eligible newborns were enrolled in FIREFISH part 2 at 14 hospitals across 10 nations in Europe, North America, South America, and Asia. For babies aged 5 months to 2 years, a dosage of 02 mg/kg of risdiplam was given orally once daily; after the child turned 2, the dose was raised to 025 mg/kg. When pharmacokinetic information was available for each child, the beginning dosage for infants under 5 months old was changed from 0 mg/kg to 0 mg/kg. The statistical hierarchy's primary and secondary outcomes, which were evaluated at month 12, have been previously published. The capacity to sit unaided for at least 30 seconds, to stand alone, and to walk unassisted, as measured by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale, are the remaining secondary efficacy endpoints that were presented here. A performance requirement of 5% was used to compare these three endpoints, and statistical significance was determined by whether the lower limit of the two-sided 90% CI was higher than the 5% cutoff. This performance criterion was based on the natural history of type 1 spinal muscular atrophy.

The key findings of this study were:

1. There were 41 newborns registered in FIREFISH phase 2 between March 13 and November 19, 2018.

2. After receiving therapy for 24 months, 38 infants remained in the research, and 18 of them were able to sit alone for at least 30 seconds.

3. After receiving therapy for 24 months, no infants were able to walk or stand by themselves.

4. Upper respiratory tract infections were the most commonly reported adverse event, affecting 22 infants (54%); pneumonia, affecting 16 infants (39%) and respiratory distress, affecting three infants (7%), were the most frequently reported serious adverse events.

Reference:

Masson, R., Mazurkiewicz-Bełdzińska, M., Rose, K., Servais, L., Xiong, H., Zanoteli, E., Baranello, G., Bruno, C., Day, J. W., Deconinck, N., Klein, A., Mercuri, E., Jaber, B., Kletzl, H., Gaki, E., … FIREFISH Study Group (2022). Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. The Lancet. Neurology. https://doi.org/10.1016/S1474-4422(22)00339-8