Risdiplam over 24 months improved motor function in infants with type 1 SMA

Daily treatment with risdiplam over 24 months resulted in improved motor function and achievement of developmental motor milestones in infants with type 1 spinal muscular atrophy, according to a study published in The Lancet Neurology.

“Type 1 spinal muscular atrophy is a severe form of spinal muscular atrophy with symptoms usually occurring by 6 months of age,” Riccardo Masson, MD, of the developmental neurology unit at the Carlo Besta Neurological Institute in Milan, and colleagues wrote. “Untreated infants are unable to sit without support and have reduced life expectancy.”

As a follow-up to the second part of the ongoing FIREFISH study, in which infants with type 1 SMA were able to sit unsupported for at least 5 seconds after 12 months of treatment with risdiplam, Masson and researchers sought to determine the safety and efficacy of risdiplam in study participants over 24 months of treatment.

The multicenter, open-label study included 41 infants aged 1 to 7 months, all of whom had a genetically confirmed diagnosis of SMA and two SMN2 gene copies, who were enrolled between March and November 2018 from 14 hospitals in 10 countries across Europe, North America, South America and Asia.

Oral risdiplam was given once a day at 0.2 mg/kg for infants aged 5 months to 2 years. At 2 years of age, the dose was increased to 0.25 mg/kg. Infants aged 1 to 3 months started at 0.04 mg/kg, while those aged 3 to 5 months started at 0.08 mg/kg. The starting dose was adjusted to 0.2 mg/kg once pharmacokinetic data were available for each infant.

Secondary outcomes of interest at 24 months included the ability to sit without support for at least 30 seconds, to stand alone and to walk alone, which were assessed by the Bayley Scales of Infant and Toddler Development (third edition gross motor subscale). Researchers compared these endpoints with a performance criterion of 5% based on the natural history of type 1 SMA.

At 24 months, 38 infants remained in the study, 18 of whom were able to sit without support for at least 30 seconds (90% CI, 31-58). No infants could stand alone or walk alone after 24 months of treatment. The most common adverse events included upper respiratory tract infection, reported in 22 infants (54%), while the most common serious adverse events were pneumonia in 16 infants and respiratory distress in three infants.

“These findings show meaningful gains in motor function beyond month 12, confirming that longer-term treatment with risdiplam benefited patients with type 1 spinal muscular atrophy,” Masson and colleagues wrote.