PTC Therapeutics announced the U.S. Food and Drug Administration (FDA) has approved Evrysdi? (risdiplam), the first at-home, orally administered treatment for spinal muscular atrophy (SMA) in adults and children 2 months and older. Evrysdi showed clinically meaningful improvements in motor function and obtainment of developmental milestones across two trials in patients age two months and above and across all levels of disease severity, including types 1, 2, and 3 SMA. Infants achieved key motor milestones not normally seen in the natural course of the disease, such as the ability to sit without support. Evrysdi also preserved vital functions and improved survival at 12 months. In particular, Evrysdi improved survival without permanent ventilation compared to natural history when measured at 12 and 23 months.

"Today marks an incredibly important moment for the broader SMA patient community that had been in dire need of safe and effective treatment options," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics. "We are appreciative of the patients, physicians and others involved with its development, and our partners at the SMA Foundation and Roche. We are proud that the first oral treatment for spinal muscular atrophy patients was discovered through our splicing platform. I believe that this is one of the most innovative products in the pharmaceutical industry and we are gratified to have played a key role in its discovery and development."

Evrysdi has been studied in a robust clinical trial program in SMA with more than 450 patients and subjects. The program includes infants aged 2 months to adults aged 60 with a range of symptoms and motor function including patients with scoliosis or joint contractures. Patients previously treated for SMA with other medications were also included. The approval is based on results from two clinical studies designed to represent a broad spectrum of patients living with SMA: FIREFISH in symptomatic infants aged 2 to 7 months; and SUNFISH, in children and adults aged 2 to 25 years. SUNFISH is the first and only placebo-controlled trial to include adults with types 2 and 3 SMA.

In FIREFISH, 41% (7/17) of infants treated with the therapeutic dose achieved the ability to sit without support for at least 5 seconds as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Additionally, 90% (19/21) of infants were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older. As described in the natural history of untreated infantile-onset SMA, infants would not be expected to be able to sit independently and only 25 percent of infants would be expected to survive without permanent ventilation beyond 14 months of age. In SUNFISH, children and adults treated with Evrysdi experienced a statistically significant and clinically meaningful improvement in motor function at 12 months (1.55 point mean difference; p = 0.0156) compared to placebo, as measured by a change in baseline on the Motor Function Measure-32 (MFM-32) scale.

Evrysdi demonstrated a favorable efficacy and safety profile, with the safety profile established across the FIREFISH and SUNFISH trials. The most common adverse reactions were fever, diarrhea, and rash in later-onset SMA. In infantile-onset SMA, the most common adverse events were similar and also included upper respiratory tract infection, pneumonia, constipation, and vomiting. There were no treatment-related safety findings leading to withdrawal from any study. Ophthalmological monitoring is not required.

Evrysdi will be available in the United States within two weeks for direct delivery to patients' homes through Accredo Health Group Inc., an Express Scripts specialty pharmacy.

Evrysdi will be marketed in the United States by Genentech, a member of the Roche Group, and received an orphan drug designation from FDA in 2017. Outside the United States, Roche holds global commercialization rights to risdiplam, and the European Medicines Agency (EMA) previously granted PRIME (Priority Medicines) designation to risdiplam in 2018 for the treatment of people with SMA and an orphan drug designation in 2019. The submission of a marketing authorization application (MAA) to EMA for risdiplam is pending. At this time, Roche has submitted applications for approval in Brazil, Chile, China, Indonesia, Russia, South Korea and Taiwan, China Region of China.

Evrysdi is a product of the SMA collaboration between PTC, the SMA Foundation, and Roche.

Evrysdi is a survival motor neuron 2 (SMN2)-directed RNA splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is designed to distribute evenly to all parts of the body, including the central nervous system (CNS). Evrysdi is administered daily at home in liquid form by mouth or feeding tube.