Elizabeth Berry-Kravis, MD, PhD, Pediatric Neurologist at Rush University Medical Center, discusses the development of an investigational drug for Fragile X syndrome (FXS).

FXS is a rare genetic condition involving mutations in part of the X chromosome. This condition causes a range of developmental problems including learning disabilities and cognitive impairment. It is the most common form of inherited intellectual disability in males and a significant cause of intellectual disability in females. Other signs and symptoms may include symptoms of autism spectrum disorders, seizures, and characteristic physical features. FXS is caused by a change in the FMR1 gene. There are currently no approved therapies for the condition.

Zatolmilast (BPN14770) is the first and only selective PDE4D inhibitor being investigated for the treatment of FXS. The therapy has been granted Fast Track designation, as well as Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. Food and Drug Administration (FDA).

As noted by Dr. Berry-Kravis, a phase 2 clinical trial concluded that the drug was safe and effective in improving cognitive abilities in patients with FXS. Pivotal phase 2b/3 studies are now recruiting patients - one for adolescents (NCT05163808)  and one for adults (NCT05358886) across 15 sites in the US. To increase the accessibility of these studies to patients,  several protocols have been amended to the clinical program, including:

Lowering the eligibility age from 12 to 9 years
Reduced the number of on-site visits by adding remote options
Extending the open-label extension period
Covering travel services

Chapters:
Fragile X Syndrome Overview 00:00
Zatolmilast Drug Development 3:56