Roche announces results from Evrysdi study in infants with Type 1 spinal muscular atrophy (SMA) published in NEJM

Roche announced that the New England Journal of Medicine has published Evrysdi (risdiplam) data from the dose finding Part 1 of the pivotal FIREFISH study in infants with symptomatic Type 1 spinal muscular atrophy (SMA)

The data show that treatment with Evrysdi at 12 months helped 90% (19/21) of these infants survive without permanent ventilation and 33% (7/21) sit without support for at least 5 seconds, which is not normally seen in the natural course of the disease. The study also found that treatment with Evrysdi increased the levels of survival of motor neuron (SMN) protein by a median 1.9-fold from baseline in the high-dose cohort at 12 months. The exploratory efficacy analysis found that after 12 months of treatment, seven (33%; 7/21) infants were able to sit without support for at least 5 seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III). All seven infants who achieved this milestone received the high dose (41%; 7/17), which was the dose selected for the confirmatory Part 2 of the study. Nine of the infants in the high-dose cohort (53%; 9/17) had upright head control after 12 months of treatment, and one infant (6%; 1/17) was able to stand (bearing weight), as assessed by the Hammersmith Infant Neurological Examination Module 2 (HINE-2).

In the low- and high-dose cohorts, no infant lost the ability to swallow over 12 months , and 86% (18/21) were able to feed orally, either exclusively or in combination with a feeding tube at 12 months. In addition, 90% (19/21) of infants were alive without permanent ventilation after 12 months of treatment with Evrysdi. Three infants experienced fatal complications of their disease after approximately one, eight and 13 months of treatment, respectively. An additional infant passed away after the data cut-off with death occurring approximately 3.5 months after receiving the last dose of study drug. None of these have been attributed by the investigator as related to Evrysdi.

The researchers also assessed motor function with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a scale used for infants with Type 1 SMA. Results showed that 11 out of the 21 infants (52%) had a CHOP-INTEND total score of 40 points or higher. The CHOP-INTEND scale ranges from 0 to 64, with higher scores indicating better function.

The most common adverse events included fever (pyrexia; 52%), upper respiratory tract infections (43%), diarrhea (29%), cough (24%), vomiting (24%), constipation (19%) and pneumonia (19%). In total, 24 serious adverse events were reported as of the clinical data cut-off, with the most common including pneumonia in three infants and respiratory tract infection, viral respiratory tract infection, acute respiratory failure and respiratory distress in two infants each.

Among the 21 infants enrolled in Part 1 of the FIREFISH study, the median duration of treatment was 14.8 months at the time of analysis. The median age at enrollment was 6.7 months and symptom onset between the ages of 28 days to 3 months.

See- “Risdiplam in Type 1 Spinal Muscular Atrophy”- Giovanni Baranello, M.D., Ph.D., Basil T. Darras, M.D., et al., for the FIREFISH Working Group-February 24, 2021 DOI: 10.1056/NEJMoa2009965.