Shionogi and Guardian Angels Launch First-Ever Human Drug Study for Jordan’s Syndrome

Shionogi & Co., Ltd. and Jordan’s Guardian Angels announced a research collaboration between their organizations and the first-ever clinical trial evaluating an investigational drug for PPP2 syndrome type R5D (Houge-Janssens syndrome 1, HJS1), commonly referred to as Jordan’s Syndrome.

The Phase 2 randomized, double-blind, placebo-controlled study will evaluate the safety and tolerability of zatolmilast (BPN14770), an investigational selective PDE4D inhibitor, in people with Jordan’s Syndrome. The study will also explore preliminary assessments of efficacy and obtain pharmacokinetic and biomarker data.

Zatolmilast was discovered by Tetra Therapeutics, which was acquired by Shionogi in 2020. The drug is also being evaluated for Fragile X syndrome (FXS), the leading cause of inherited intellectual disabilities, in a pivotal Phase 2b/3 program in the U.S.

Jordan’s Guardian Angels, the only patient advocacy group for Jordan’s Syndrome, an ultra-rare genetic disorder, has dedicated the past eight years to raising awareness and securing funding for research. This clinical program is the result of an innovative, groundbreaking collaboration with 10 research and academic institutions: Columbia University, Seattle Children’s Hospital, Boston Children’s Hospital, UC Davis, University of South Alabama, Vanderbilt University, the University of Wisconsin Madison, Katholieke Universiteit Leuven, the University of Iowa and the University of Rochester, and was supported by funding from the state of California.

“When my daughter, Jordan, was finally diagnosed after years of testing, it became my family’s mission to cultivate and grow a supportive community with the shared goal of advancing the understanding of this disorder and progressing towards potential treatment options,” said Joe Lang, a co-founder of Jordan’s Guardian Angels and father of Jordan, one of the first patients to be diagnosed with the condition. “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.”

The Phase 2 study of zatolmilast in Jordan’s Syndrome will enroll 30 participants in early 2025 aged 9-45 years with a confirmed/documented history of PPP2R5D neurodevelopmental disorder. Participants will receive a weight-adjusted dose of the study drug or placebo twice daily during the 24-week double-blind period. Participants will have the opportunity to continue in a 24-week open-label extension period. The study is expected to conclude in late 2026. See ClinicalTrials.gov ID: NCT06717438 for additional study details and locations.

Jordan’s Syndrome is characterized by global developmental delays, seizures, physical abnormalities, vision problems, muscle weakness, attention disorder, social and sensory challenges commonly associated with autism, disordered sleep and feeding difficulties. Symptoms and severity vary depending on the individual.

There are currently no specific medications or curative treatments available for people with Jordan’s Syndrome. While only about 350 people have been diagnosed with Jordan’s Syndrome globally, it is estimated that many more go undiagnosed. Jordan’s Syndrome is difficult to diagnose because symptoms can vary widely, and the condition can co-exist with other developmental disorders like autism spectrum disorder. In addition, whole-exome sequencing or diagnostic testing for a panel of genes associated is needed to identify the specific mutation in the PPP2R5D gene to confirm a Jordan’s Syndrome diagnosis, a test that may be difficult to access.

“We are excited to embark on the next step in our journey to develop a treatment for Jordan’s Syndrome,” said Wendy Chung MD, PhD, Chief of the Department of Pediatrics at Boston Children’s Hospital, Professor of Pediatrics at Harvard Medical School and lead principal investigator of the study. “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.”

Stefan Strack, PhD, Vice Chair of Neuroscience and Pharmacology at the University of Iowa, led preclinical research involving zatolmilast to assess cognitive function and underlying disease processes in animal models for Jordan’s Syndrome, paving the way for this Phase 2 study.
“Shionogi is honored to partner with Jordan’s Guardian Angels on this historic study as we work together to advance our shared commitment to helping patients and families affected by Jordan’s Syndrome,” said Juan Carlos Gomez, MD, MBA, Chief Medical Officer, Shionogi & Co. Ltd. “Through this expansion of our zatolmilast clinical program, we hope to bring meaningful advances to the Jordan’s Syndrome community.”

The U.S. Food and Drug Administration (FDA) recently granted zatolmilast Rare Pediatric Disease Designation (RPD) for the treatment of Jordan’s Syndrome, a designation granted for serious and life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people in the United States.