Infants with severe type 1 spinal muscular atrophy (SMA) treated with risdiplam continue to demonstrate modest improvements in motor function after two years of treatment, new research shows.
The FIREFISH study enrolled 41 infants aged 1-7 months with a genetically confirmed diagnosis of type 1 SMA and two SMN2 gene copies.
As previously reported in the limbic [link here], 29% of infants attained the ability to sit without support for at least 5 seconds after 12 months of risdiplam treatment.
Now, a study published in Lancet Neurology [link here], reports that 44% of infants were able to sit without support for at least 30 seconds after two years of treatment.
“Without treatment, children with type 1 spinal muscular atrophy are never able to sit without support, and thus the ability to achieve sitting is an important motor milestone in treated type 1 spinal muscular atrophy,” the study said.
It said that no infants could stand alone or walk alone after 24 months of treatment.
However, more infants had achieved “standing with support” (15% v 5%) and “cruising” (2% v 0%) after 24 months compared to 12 months of treatment.
The study said any clinically meaningful gains in motor function indicate “a clear deviation from natural history data” where achievement of major motor milestones is rarely observed.
Similar to after 12 months treatment, most children were able to feed orally after 24 months of treatment (85% v 83%) and were without permanent ventilation (90% v 92%).
A Comment article in the journal [link here] noted that risdiplam is the only oral agent for SMA.
“The administrative route can be a factor for adherence; for example, adherence to nusinersen, which is delivered intrathecally, can drop to less than 50% after 12 months of treatment,” it said.
“Finally, many patients and families see risdiplam as an option to add on after one or more other drugs have been used, although there is currently no scientific evidence that combining disease- modifying therapies for spinal muscular atrophy is either safe or effective.”
“An interesting and important observation when comparing results reported at month 12 with those reported at month 24, is that there is a cumulative effect over time—the more doses received, the better the motor outcome.”
“This effect was also seen with nusinersen. Therefore, the two key principles of treating spinal muscular atrophy are (1) the earlier the better and (2) prolonged use of disease-modifying therapy is better.”
It reiterated that newborn screening was crucial to allow for the earliest possible treatment.
It was also important to remember that none of the disease-modifying therapies or their combinations were curative, therefore multidisciplinary management of pulmonary, nutritional, orthopaedic, and cognitive complications remain essential for all patients.
Risdiplam, which increases the level of functional survival of motor neuron (SMN) protein, was listed on the PBS in August 2021 for <18 years.