New Evrysdi Data Shows Improvement in Motor Function Over Time for SMA Patients

Rare Daily Staff

Genentech said two-year data from part 2 of FIREFISH, its phase 2/3 global study evaluating Evrysdi in infants aged 1-7 months at enrollment with symptomatic type 1 spinal muscular atrophy, showed continued improvement to motor function between months 12 and 24, including the ability to sit without support.

The study also showed Evrysdi continued to improve survival, improve ability to feed orally and reduce the need for permanent ventilation. Exploratory data suggested Evrysdi continued to improve the ability to swallow and reduce hospitalizations compared to the natural course of Type 1 SMA.

The findings from FIREFISH Part 2 and will be presented at the 73rd American Academy of Neurology Annual Meeting being held virtually April 17 to 22.

“The natural course of type 1 SMA shows us that, sadly, without treatment children are never able to sit without support and typically don’t survive beyond the age of two,” said FIREFISH investigator Basil Darras, professor of Neurology at Harvard Medical School and director of the Spinal Muscular Atrophy Program at Boston Children’s Hospital. “It is encouraging to see that infants continued to improve after 12 months of treatment, with twice as many of those who received Evrysdi for two years able to sit without support for at least five seconds.

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

The U.S. Food and Drug Administration (FDA) approved Evrysdi for the treatment of SMA in adults and children 2 months of age and older in August of 2020. In March 2021, the European Commission approved Evrysdi for the treatment SMA in patients 2 months of age and older with mutations in chromosome 5q, with a clinical diagnosis of SMA type 1, type 2 or type 3 or with one to four SMN2 copies. Evrysdi has been approved in 39 countries and submitted in a further 33 countries.

The primary endpoint of the FIREFISH study was the percentage of infants able to sit without support for at least five seconds at month 12. At 12 months, infants treated with Evrysdi demonstrated improved ability to sit without support for at least five and 30 seconds.

Twenty-four month data showed continued improvements from month 12, with 61 percent vs. 29 percent able to sit without support for at least five seconds and 44 percent vs. 17 percent able to sit without support for at least 30 seconds, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III).

Infants treated with Evrysdi maintained the ability to feed orally (92 percent) at month 24. Further, exploratory data suggest similar maintenance in ability to swallow (95 percent). In the natural course of the disease, infants with type 1 SMA older than 12 months generally require feeding support.

 Ninety-three percent of infants were alive after 24 months of treatment. Eighty-three percent of patients were alive and free from permanent ventilation after 24 months, an improvement compared to the natural course of the disease. There were no new deaths between months 12 and 24. Without treatment, the median age of death or permanent ventilation is 13.5 months.

In addition, fewer hospitalizations were observed during the second year of treatment with Evrysdi compared with the natural course of the disease, with 34 percent of infants not requiring hospitalization during 24 months of treatment.

Safety for Evrysdi was consistent with its established safety profile.

“These data highlight the real-world impact of this transformative medicine in babies with the most severe form of SMA. For example, all infants alive after 24 months of treatment were able to swallow which can help them to feed orally rather than through a tube,” said Levi Garraway, chief medical officer and head of Global Product Development. “These results increase our understanding of how this first-of-its-kind treatment can extend the lives of babies with type 1 SMA, providing much needed hope for their families.”

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