RARE Daily

FDA Approves Expansion of Evrysdi Label

May 31, 2022

The U.S. Food and Drug Administration has approved Genentech’s Evrysdi to treat babies with the rare neuromuscular disease spinal muscular atrophy less than two months of age, making it the first medicine administered at home for these patients.

Photo: Richard Finkel, RAINBOWFISH principal investigator and director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital.

The expanded approval was based on a priority review of a supplemental New Drug Application that included interim efficacy and safety data showing that the majority of pre-symptomatic babies treated with Evrysdi for at least one year achieved key milestones such as sitting, standing, and walking.

Spinal muscular atrophy (SMA) is a severe, progressive 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 survival motor neuron (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 SMN protein in the central nervous system (CNS) and peripheral tissues as demonstrated in animal models. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. It is currently approved in 81 countries and is under review in 27 countries.

Evrysdi was first approved in August 2020 for individuals with all types of SMA who are two months and older. To date, more than 5,000 people have been treated with Evrysdi in clinical trials, compassionate use or real-world settings.

Of the six babies with 2 or 3 copies of the SMN2 gene in the RAINBOWFISH study interim data set, all were able to sit after one year of treatment with Evrysdi, 67 percent could stand and half of infants could walk independently. All infants were alive at 12 months without permanent ventilation.

“The approval of Evrysdi for pre-symptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” said Richard Finkel, RAINBOWFISH principal investigator and director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital. “With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed.”

As part of the label extension, the Evrysdi prescribing information has also been updated to include recent two-year pooled data from Parts 1 and 2 of the FIREFISH study, which demonstrate long-term efficacy and safety in symptomatic infants with Type 1 SMA. The study enrolled 58 babies aged 1 to 7 months and after two years of treatment with Evrysdi at the recommended dose, 60 percent of infants were able to sit without support for 5 seconds, 40 percent for 30 seconds, and 28 percent of infants were able to stand. Without treatment, infants do not achieve these milestones in the natural history of the disease. There were no treatment-related adverse events leading to withdrawal. The most common adverse reactions were upper respiratory tract infection (including nasopharyngitis, rhinitis), lower respiratory tract infection (including pneumonia, bronchitis), constipation, vomiting, and cough.

Author: Rare Daily Staff

Stay Connected

Sign up for updates straight to your inbox.