Risdiplam Improvements in Motor Function Continue Over 1 Year of Treatment in Infancy to Adulthood

In the JEWELFISH study (NCT03032172), individuals age 1 to 60 years with spinal muscular atrophy (SMA) who were treated with risdiplam (Evrysdi; Genentech, South San Francisco, CA) had more than a twofold increase in SMN protein levels. Interim exploratory efficacy data showed stabilization in motor function at 1 year of treatment as measured by change from baseline in motor function measure (MFM-32). 

In the RAINBOWFISH open-label study (NCT03779334), evaluating risdiplam treatment in the first 6 weeks of life for infants with presymptomatic SMA, age-appropriate motor milestones occurred. All 5 infants treated for 12 months can sit without support, roll over, and crawl. Standing unaided and walking independently has been achieved by 4 of the 5 children. The maximum score on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) has been achieved by 4 of the children, and the fifth has a score of 63. 

“These data from JEWELFISH add to the growing body of evidence supporting the use of Evrysdi in patients from 1 to 60 years of age,” said Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of Global Product Development. “Moreover, the early findings from RAINBOWFISH in presymptomatic babies under 2 months old are very encouraging. Altogether, we are hopeful that Evrysdi will continue to help address unmet treatment needs of the diverse SMA community.”

In the RAINBOWFISH trial, 2 infants had 2 SMN copies and 3 had more than 2 copies. The JEWELFISH study enrolled participants with SMA types 1 through 3 who received prior treatment across a wide range of ages and disease severities. Of the 174 participants enrolled, 30% were teenagers and 35% were adults, and 62% had a Hammersmith Functional Motor Scale – Expanded (HFMSE) score of less than 10 at baseline, 80% had scoliosis, and 47% had undergone scoliosis surgery. 
 
The most common adverse events from risdiplam treatment in the studies were abdominal pain (17%), cough (25%), diarrhea (17%), eczema (17%), gastroenteritis (17%), nasal congestion (33%), papule (rash; 17%), pyrexia (fever; 17%), teething (25%), and vomiting (25%). There were no adverse events leading to withdrawal or study discontinuation.