Roche today announced interim clinical data from the dose-finding parts of the pivotal FIREFISH and SUNFISH studies investigating risdiplam as a treatment for spinal muscular atrophy. The data were presented yesterday at the 23rd International Annual Congress of the World Muscle Society in Mendoza, Argentina.
FIREFISH Part 1
In Part 1 of the FIREFISH study in Type 1 SMA, six out of 14 enrolled infants were able to sit (with or without support), including three who achieved unassisted stable sitting after barely eight months of treatment. In addition, four infants demonstrated rolling to the side; seven kicking and six achieved upright head control. In HINE measurements, 8 out of 14 infants achieved a score of 40 or above at their eight month visit. Typically, an infant with Type 1 SMA does not demonstrate any motor improvement and can decline during this time period. The median CHOP-INTEND scores increased over time (37.5 at 6 months compared to 41.5 at 8 months). The median age at first dose in FIREFISH was 6.7 months and median treatment duration was 9.5 months. Nineteen out of 21 infants enrolled remain alive with two having discontinued due to the fatal progression of their disease. Three children are now over 24 months old. No infant has required a tracheostomy or permanent ventilation since study initiation, and no infant has lost the ability to swallow.
The most common adverse events observed during the study were fever (in 52.4% of participants), diarrhoea (26.8%), upper respiratory tract infections (19%), ear infections (14.3%), pneumonia (14.3%), constipation (14.3%), vomiting (14.3%), cough (14.3%) and upper respiratory tract inflammation (14.3%).
SUNFISH Part 1
In Part 1 of the SUNFISH study in Type 2 and 3 SMA, SMN protein median increases of greater than twofold, as measured in blood, were seen after 12 months. A very broad patient population aged between 2–24 years was included, ranging in functional status from weak non-ambulant to strong ambulant, and with varying degrees of scoliosis from none to severe. Twenty-one patients initially received lower doses of risdiplam for at least 12 weeks. Of the 30 participants treated with risdiplam for at least one year, the median change from baseline in Motor Function Measure (MFM) was a 3.1 point improvement. Sixty-three percent of patients experienced an improvement in MFM over baseline of three points or more after one year. Such improvements were seen both in the 17 participants under 12 years old and in the 13 participants above 12 years old. When considering patients who experienced any amount of improvement over baseline, the percentages were 70% overall – 76% for the younger age group and 62% for the older patients. Serious adverse events that occurred in two or more of the 51 patients exposed to risdiplam were nausea (in 4% of participants), upper respiratory tract infection (4%), and vomiting (4%). To date there have been no drug-related safety findings leading to withdrawal from any study.
Follow up is ongoing for the confirmatory Part 2 portions of both the FIREFISH and SUNFISH studies.
Read more about the ongoing risdiplam clinical trials on this page.
