Shionogi and Guardian Angels Launch First Human Drug Trial for Jordan’s Syndrome

Shionogi & Co., Ltd., based in Osaka, Japan, and Jordan’s Guardian Angels, a non-profit organization, are collaborating on a pioneering clinical trial targeting Jordan's Syndrome, also known as PPP2R5D syndrome. This rare genetic disorder, affecting developmental processes, will be the focus of a Phase 2 trial evaluating an investigational drug named zatolmilast (BPN14770), originally developed by Tetra Therapeutics before Shionogi's acquisition in 2020. Zatolmilast is a selective PDE4D inhibitor, which has also shown promise in treating Fragile X Syndrome, a leading cause of inherited intellectual disabilities, through ongoing trials in the United States.

The upcoming clinical study for Jordan’s Syndrome is set to begin in early 2025 and will include 30 participants aged 9 to 45 years, all confirmed to have a history of the PPP2R5D neurodevelopmental disorder. The trial design is randomized, double-blind, and placebo-controlled over a 24-week period, during which participants will receive a weight-adjusted dose of zatolmilast or a placebo. Following this, there is an opportunity for a 24-week open-label extension, allowing all participants to receive the investigational drug. The study aims to assess the drug's safety, tolerability, pharmacokinetics, and preliminary efficacy.

Jordan’s Guardian Angels was established to raise awareness and secure funding for research into Jordan’s Syndrome, an ultra-rare condition with symptoms ranging from developmental delays and seizures to vision problems and social challenges. As of now, no specific treatments exist for this disorder, which affects approximately 350 individuals globally. However, the actual number might be higher due to diagnostic challenges and symptom overlap with other conditions like autism. The diagnosis requires genetic testing to identify mutations in the PPP2R5D gene, a process that can be difficult to access.

This clinical effort is the result of collaboration among 10 research and academic institutions across the globe, and it is financially supported by the state of California. Joe Lang, who co-founded Jordan’s Guardian Angels and is the parent of one of the first diagnosed children, expressed optimism about the trial, highlighting its significance for the community and the advancement of treatments for rare diseases.

The U.S. Food and Drug Administration has granted zatolmilast a Rare Pediatric Disease Designation, acknowledging its potential to address serious conditions predominantly affecting children under 18, with fewer than 200,000 cases in the U.S. Such designation can accelerate the drug's development and review processes.

Dr. Wendy Chung from Boston Children’s Hospital and Harvard Medical School, a principal investigator in the study, emphasized the importance of collaborative research in reaching this milestone. Similarly, Dr. Stefan Strack from the University of Iowa highlighted preclinical research that laid the groundwork for this study, underscoring the drug’s potential to improve cognitive functions.

Shionogi’s Chief Medical Officer, Dr. Juan Carlos Gomez, expressed gratitude for the partnership with Jordan’s Guardian Angels, reaffirming the company's commitment to advancing treatments for rare conditions like Jordan's Syndrome. This trial, part of Shionogi's broader clinical program, aims to bring significant advancements to patients and families affected by this condition.