Study: Risdiplam as a Treatment for Spinal Muscular Atrophy (SMA)

Genentech has recently released the data from its SUNFISH trial, a study of the effects of risdiplam on spinal muscular atrophy (SMA) patients. Preliminary data from the JEWELFISH trial has also been analyzed and released, allowing us to learn even more about this new treatment.

About SMA

Spinal muscular atrophy (SMA) is rare genetic order that is characterized by muscle weakness and degeneration. It affects one in every 10,000 people but can vary in severity from person to person. A mutation in the SMN1 causes this condition, and it causes the loss of motor neurons in the spinal cord and brain stem. Due to this loss, muscles weaken and atrophy, specifically the muscles used for walking, breathing, swallowing, crawling, sitting up, and moving the head.

The symptoms of this condition depend on the severity and type of SMA. Type I is the most severe, and is diagnosed after birth. The symptoms of this type include developmental delay, the inability to sit up or move the head, and trouble with breathing and swallowing. Type II is diagnosed in children between six and twelve months old, and they experience trouble with standing and walking. Those who have type III are diagnosed between early childhood and adolescence and cannot walk or climb stairs independently. Type IV occurs in adults over 30 and is the least severe type. People with this form of SMA usually have mild muscle weakness, problems with breathing, twitches, or tremors.

Once these symptoms are noticed, a diagnosis is confirmed through neurological examination and genetic testing. While there is no cure for SMA, there are treatments available. Physical therapy, braces, and surgery can all help to improve movement. Noninvasive respiratory support and tracheostomies can address issues with breathing while gastrostomy can help with eating. Spinraza is the first FDA approved treatment for SMA, and Zolgensma has also recently been approved.

About Risdiplam

Risdiplam is an oral survival motor neuron-2 splicing modifier intended to improve the levels of SMN proteins within the body. It then sustains these numbers throughout the central nervous system (CNS) and surrounding tissues. There are currently four trials that are evaluating this treatment: SUNFISH, JEWELFISH, FIREFISH, and RAINBOWFISH.

About the Studies

The SUNFISH trial enrolled 231 people from the ages of two to twenty five, all of whom had SMA type 2 or 3. After a dose-finding phase, researchers moved on to test the efficacy of risdiplam over the course of 24 months. They utilized the Motor Function Measure (MFM) scale to do so.

After two years, the total change from baseline on the MFM scale was 3.99. This positive result was accompanied by a two-fold increase in SMN proteins in the blood. It is these results that make researchers confident that risdiplam can improve the lives of SMA patients.

In terms of the JEWELFISH study, 174 patients were enrolled, all of whom had received previous treatment. The goal was to evaluate safety and pharmacodynamics over twelve months. Like the SUNFISH study, researchers saw a two-fold increase in SMN proteins.

Because this treatment was granted Priority Review at the end of 2019, a decision should come from the FDA by the end of August. Researchers are very hopeful that approval will be granted, as they believe that risdiplam can improve lives.

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