Detailing findings from the secondary end points of the FIREFISH trial at 24 months, the researchers found that risdiplam treatment was associated with continued improvements in motor function and the achievement of development motor milestones.
Additional findings from the FIREFISH study have showed that infants receiving risdiplam for spinal muscular atrophy (SMA) continue to benefit from the treatment through 2 years of treatment.
The newly published results1 build on previous findings from the ongoing FIREFISH study, including safety and dose-finding data from FIREFISH part 1 and positive safety and efficacy data over 12 months of treatment from the FIREFISH part 2 primary analysis.
Detailing findings from the secondary end points of the trial at 24 months, the researchers found that risdiplam treatment was associated with continued improvements in motor function and the achievement of development motor milestones. Data from 38 infants were available at 24 months, showing that 44% were able to sit without support for at least 30 seconds, significantly higher than the 5% performance criterion.
“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,” wrote the researchers.
Gains made at 12 months continued through month 24, with an increase in the number of infants able to sit without support for at least 5 seconds—the primary end point of the FIREFISH 2 primary analysis. By 24 months of treatment, 13 more infants were able to sit without support for 5 seconds. Eight more patients achieved a Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorder score of at least 40 points—a secondary end point of the primary analysis. Most of the infants maintained their ability to swallow and feed orally at 24 months.
In an accompanying commentary,2 it was noted that improvements seen with risdiplam in the study are less pronounced than with other treatments. According to the author, milestones occurred later and among fewer patients compared with those seem among patients receiving nusinersen and onasemnogene abeparvovec in clinical trials. This difference, wrote the author, could be due to patients being enrolled at a later age in the FIREFISH study and all patients having 2 copies of the SMN2 gene, indicating more sever disease.
In the FIREFISH analysis, no infants were able to independently stand or walk by 24 months of treatment, through the researchers suggested that some or part of these milestones may be achieved with longer treatment, noting the greater number of infants having higher responses in certain Hammersmith Infant Neurological Examination, Section 2 (HINE-2) categories at 24 months than at 12 months. Three more infants were considered HINE-2 motor milestone responders by 24 months of treatment.
Reflecting on the lack of independent standing and walking seen in their patients, the researchers wrote: “This might be related to the age at disease onset, age at treatment initiation (treatment initiated 1 day after enrolment; median age at enrolment 5.3 months, IQR 4.2-6.8), and disease severity when patients started treatment (median disease duration, defined as time from symptom onset to first dose, 3.4 months, IQR 2.5-4.9).”
Throughout the course of treatment, no infants discontinued from the study due to drug-related adverse events, which occurred in 17% of infants.
The most frequently occurring adverse event was upper respiratory tract infection, reported in 54% of infants. The most common serious adverse events were pneumonia (39%), which dropped in incidence from the first year of treatment, and respiratory distress (7%).
1. Masson R, Mazurkiewicz-Bełdzińska M, Rose K, et al. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet Neurol. 2022;21(12):1110-1119. doi:10.1016/S1474-4422(22)00339-8
2. Iannaccone S. New results for risdiplam in spinal muscular atrophy. Lancet Neurol. 2022;21(12):1065-1066. doi:10.1016/S1474-4422(22)00427-6