Rare Daily Staff

Genentech reported preliminary efficacy data from its ongoing RAINBOWFISH study of Evrysdi showed babies from birth to 6 weeks with pre-symptomatic spinal muscular atrophy treated for 12 months achieved age-appropriate motor milestones.

These data were presented at the recent 2021 Virtual SMA Research & Clinical Care Meeting. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube. Evrysdi is designed to treat SMA by increasing and sustaining the production of the survival motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

The European Medicines Agency granted PRIME designation to Evrysdi in 2018. The U.S. Food and Drug Administration granted Evrysdi Orphan Drug designation in 2017. Evrysdi won approval in 44 countries and submitted in a further 32 countries.

The RAINBOWFISH data showed that of the five babies treated with Evrysdi for at least 12 months, all achieved sitting without support, rolling, and crawling. Of the five, two had 2 SMN copies and three had more than two copies. Four of the infants were able to stand unaided and walk independently. In addition, four babies reached a maximum score of 64 on the CHOP-INTEND scale, and one scored 63.

Data on the primary endpoint—the number of infants sitting without support for at least five seconds—will be reported when all primary analysis patients have reached one year of treatment. Recruitment for RAINBOWFISH is ongoing. 

The overall adverse events profile of Evrysdi treatment in pre-treated patients was consistent with that of treatment-naïve patients in FIREFISH and SUNFISH.

Genentech also reported interim data from its ongoing JEWELFISH study, an open-label study primarily evaluating the safety of Evrysdi in people aged 1 to 60 years who have been previously treated with another SMA-targeting therapy, including nusinersen and onasemnogene abeparvovec. It showed the safety profile of Evrysdi and increase in SMN protein levels are consistent with those observed in other Evrysdi studies.

The JEWELFISH study enrolled the broadest patient population ever studied in an SMA trial, including patients with SMA types 1-3 who received prior treatment across a wide range of ages and disease severities. Of the 174 people enrolled, 30 percent were teenagers and 35 percent adults. Seventy-six people had previously been treated with nusinersen and 14 with onasemnogene abeparvovec. Evrysdi led to a sustained greater than two-fold increase in median SMN protein levels versus baseline in all patients who received prior treatment, irrespective of which treatment was previously received or SMA type. 

“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, Genentech’s chief medical officer and head of Global Product Development. “Moreover, the early findings from RAINBOWFISH in pre-symptomatic babies under two months old are very encouraging.

Photo: Levi Garraway, Genentech’s chief medical officer and head of Global Product Development

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