In a landmark development for rare disease treatment, Shionogi & Co., Ltd. and Jordan's Guardian Angels have announced the initiation of the first-ever human drug trial for Jordan's Syndrome, an ultra-rare genetic neurodevelopmental disorder. The Phase 2 clinical study will evaluate zatolmilast (BPN14770), a selective PDE4D inhibitor, marking a significant milestone in addressing this challenging condition.
The trial, registered under ClinicalTrials.gov ID: NCT06717438, will assess the safety and tolerability of zatolmilast in 30 participants aged 9-45 years with confirmed PPP2R5D neurodevelopmental disorder. The study design includes a 24-week double-blind, placebo-controlled period followed by a 24-week open-label extension phase.
Understanding Jordan's Syndrome
Jordan's Syndrome, also known as PPP2 syndrome type R5D or Houge-Janssens syndrome 1, affects approximately 350 diagnosed individuals globally. The condition manifests through various symptoms, including global developmental delays, seizures, physical abnormalities, vision problems, and muscle weakness. Many patients also experience attention disorders and autism-like social and sensory challenges.
Dr. Wendy Chung, Chief of Pediatrics at Boston Children's Hospital and the study's lead principal investigator, emphasized the significance of this development: "This milestone would not be possible without the collaboration of our research teams, the dedication of our families, and this new partnership with Shionogi, an organization with a history of delivering scientific breakthroughs for patients around the world."
Innovative Research Collaboration
The clinical program emerged from a groundbreaking collaboration between ten prestigious research institutions, including Columbia University, Seattle Children's Hospital, and Boston Children's Hospital. Preclinical research led by Dr. Stefan Strack at the University of Iowa provided crucial data on cognitive function and disease processes in animal models, paving the way for this human trial.
Joe Lang, co-founder of Jordan's Guardian Angels and father of Jordan, one of the first diagnosed patients, shared his perspective: "While we know this is just the beginning, this is a profound moment for our community, and we are hopeful for our children's futures and the future of rare disease drug development."
Drug Development and Regulatory Status
Zatolmilast, discovered by Tetra Therapeutics (acquired by Shionogi in 2020), has already shown promise in treating Fragile X syndrome. The FDA has granted the drug Rare Pediatric Disease Designation for Jordan's Syndrome treatment, acknowledging the critical need for therapeutic options in this underserved patient population.
Dr. Juan Carlos Gomez, Chief Medical Officer at Shionogi, stated, "Through this expansion of our zatolmilast clinical program, we hope to bring meaningful advances to the Jordan's Syndrome community."
Trial Design and Timeline
The study will implement a weight-adjusted dosing regimen, with participants receiving the study drug or placebo twice daily. The comprehensive trial design aims to gather essential data on safety, efficacy, pharmacokinetics, and biomarkers. Expected to conclude in late 2026, this study represents a crucial step toward developing the first targeted treatment for Jordan's Syndrome.
The research community anticipates that this pioneering study could not only benefit Jordan's Syndrome patients but also contribute valuable insights to the broader field of rare disease drug development.
