Children Treated With Risdiplam Continue Having Improved Motor Function
In part 2 of the FIREFISH study (NCT02913482), infants aged 1 to 7 months with symptomatic type 1 spinal muscular atrophy (SMA) treated with risdiplam (Evrysdi; Genentech, South San Francisco, CA) continued meeting motor milestones. Between 12 and 24 months after treatment, the children gained the ability to sit without support for at least 5 or 30 seconds. Improved ability to swallow and reduced hospitalizations compared with the natural course of type 1 SMA were also observed.
At 24 months after treatment, children had continued improvement 44% (18/41) able to sit without support for at least 30 seconds, and 61% (25/41) able to sit without support for at least 5 seconds. The ability to stand with support has been achieved by 15% of those treated in infancy. This is 3 times the rate of achieving these motor milestons than is seen during untreated SMA. Infants treated with risdiplam also maintained the ability to feed orally (92%; 35/38) at month 24.
The survival rate for infants treated for 24 months was 93% (38/41) and 83% were free of permanent ventilation after 24 months, an improvement compared with the natural course of the disease. No new deaths occurred between months 12 and 24, compared with a median age of death or permanent ventilation of 13.5 months in the natural history of type 1 SMA. Rates of hospitalization were also lower than in the natural history, although 66% (27/41) of the children did have a hospitalization during the second year of treatment.
“The natural course of type 1 SMA shows us that, sadly, without treatment children are never able to sit without support and typically don’t survive beyond the age of 2 years,” said FIREFISH investigator Dr. Basil Darras, MD professor of Neurology at Harvard Medical School and director of the SMA Program at Boston Children's Hospital. “It is encouraging to see that infants continued to improve after 12 months of treatment, with twice as many of those who received Evrysdi for 2 years able to sit without support for at least 5 seconds. Infants treated with Evrysdi also experienced a range of improvements in motor function abilities, a reduction in serious events typically caused by disease progression, such as the need for permanent ventilation or hospitalization, and increased rate of survival.”
The most common adverse events of risdiplam in this trial have been bronchitis (15%), constipation (29%), diarrhea (15%), nasopharyngitis (17%), pneumonia (46%), pyrexia (44%), rhinitis (12%), and upper respiratory tract infection (54%). The most common serious adverse events were pneumonia (39%) and respiratory distress (7%). There were no drug-related adverse events leading to withdrawal or treatment discontinuation.
These data were presented at the virtual 2021 American Academy of Neurology (AAN) Virtual Annual Meeting April 17-22, 2021.