Treatment for Pre-symptomatic Spinal Muscular Atrophy Patients Granted FDA Priority Review

PTC Therapeutics Inc. has just announced that their supplemental new drug application for Evrysdi (risdiplam) has been given priority review by the FDA. The aim is to expand the indication of Evrysdi so that it can be used as a therapy for patients under the age of 2 months who are diagnosed with spinal muscular atrophy (SMA) who haven’t yet experienced symptoms.

If this application is approved, it will become the very first therapy for pre-symptomatic SMA patients which can be administered at home.

Spinal Muscular Atrophy

SMA is a rare and progressive neuromuscular condition. It is the result of a mutation in the SMN1 gene which causes the body to be unable to produce the SMN protein.

In healthy individuals, this protein allows the muscles to be properly controlled and permits movement.

Without the protein, SMA patients have nerve cells which don’t function as they should. It causes progressive muscle weakness. This muscle weakness can affect mobility and every organ in the body.


Evrysdi is an SMN2-directed RNA splicing modifier. It works to increase the production of the SMN protein, which those with SMA are deficient in.

This therapy is administered either orally or via a feeding tube. This liquid treatment distributes evenly across the body and the central nervous system.

Evrysdi is FDA-approved as an SMA treatment for those over the age of 2 months.


The supplemental new drug application included interim data from the RAINBOWFISH clinical trial. This study has demonstrated that 80% of the SMA infants reached motor milestones after being given Evrysdi for one year. These milestones include rolling, sitting/standing without assistance, crawling, and walking without assistance.

This trial is still currently recruiting patients. It is an open-label, multi-center trial which is evaluating the safety, efficacy, pharmacodynamics, and pharmacokinetics of Evrysdi in 25 patients who are diagnosed with SMA but don’t yet have symptoms.

Other Clinical Studies


The FIREFISH trial had two parts. Both assessed Evrysdi as a therapy option for newborns with Type 1 SMA.

The first part was a dose-escalation phase including 21 patients. The aim of this part of the trial was to examine the safety of the therapy and which dose should be used in the second portion of the study.

The second part of the trial included 41 patients. All were treated for two years. Following the trial, there was an open-label extension for participants. The primary endpoint of this part of the trial was to examine the efficacy of Evrysdi (which was assessed by the ability to sit without support at the one-year mark). This trial achieved its primary endpoint.


This trial was also a 2 part investigation examining the therapy in patients between 2 and 25 years of age diagnosed with Type 2 and Type 3 SMA.

Part 1 included 51 patients and was a dose-escalation phase.

Part 2 of the trial included 180 patients. The primary aim was to evaluated motor function after 1 year of treatment. This trial achieved its primary endpoint.

Across the FIREFISH and the SUNFISH trial, the safety of Evrysdi was documented. Common AEs for those with late-onset SMA and infantile-onset SMA included rash, fever, and diarrhea. Other common AEs included constipation, vomiting, pneumonia, and upper respiratory tract infections.


The trial has just completed recruitment. 174 patients are participating in this investigation which will examine the safety, pharmacodynamics, pharmacokinetics, and tolerability of the treatment. All participants have diagnosed SMA, have tried other therapies within the 90 days preceding the trial, and are between the ages of 6 months and 60 years.

You can read more about these trials and this investigative therapy for SMA here.

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