FDA Grants Orphan Drug Designation to PB-TURSO for Wolfram Syndrome

The Food and Drug Administration (FDA) has granted orphan drug designation for combination of phenylbutrate (PB) and tauroursodeoxycholic acid (TUDCA) (AMX0035; Amylyx Pharmaceuticals, Inc., Cambridge, MA) for  Wolfram syndrome, a rare autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, neurodegeneration, sensorineural deafness, and other conditions. 

Genetic and experimental evidence suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome. The prognosis of the disease is poor, and many patients die prematurely.  

The therapy is an investigational drug designed to reduce neuronal death and dysfunction. The drug targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and other neurodegenerative diseases.

“There is a critical unmet need for people living with Wolfram syndrome, a rare genetic disease in which many patients die prematurely with severe neurological disabilities,” said Fumihiko Urano, MD, PhD, professor of medicine, pathology, and immunology at Washington University School of Medicine. “Endoplasmic reticulum (ER) dysfunction is a critical component of Wolfram syndrome. AMX0035 is designed to target the ER stress, and preclinical data suggest that it may be a promising approach to halt the irreversible progression of optic nerve atrophy in patients with Wolfram syndrome.”