Zatolmilast Clinical Trial Offers Hope for Jordan’s Syndrome Patients
Shionogi & Co., Ltd., in collaboration with Jordan’s Guardian Angels, has announced a groundbreaking research initiative and the first-ever clinical trial to evaluate an investigational drug for PPP2R5D-related neurodevelopmental disorder, commonly known as Jordan’s Syndrome. This Phase 2 randomized, double-blind, placebo-controlled study will assess the safety, tolerability, and preliminary efficacy of zatolmilast (BPN14770), a selective PDE4D inhibitor, in individuals with Jordan’s Syndrome. The trial, set to begin in early 2025, will also explore pharmacokinetic and biomarker data, marking a significant milestone in the quest for a treatment for this ultra-rare genetic disorder.
Zatolmilast, originally discovered by Tetra Therapeutics and later acquired by Shionogi in 2020, is also being investigated for Fragile X syndrome (FXS), the leading cause of inherited intellectual disabilities. The drug’s potential to address cognitive and developmental challenges in rare genetic disorders has garnered significant attention from the scientific community.
Jordan’s Guardian Angels, the sole patient advocacy group for Jordan’s Syndrome, has played a pivotal role in advancing research and raising awareness about the condition. Over the past eight years, the organization has collaborated with 10 leading research and academic institutions, including Columbia University, Boston Children’s Hospital, and the University of Wisconsin Madison, to lay the groundwork for this clinical trial. Funding from the state of California has further supported this innovative initiative.
Joe Lang, co-founder of Jordan’s Guardian Angels and father of Jordan, one of the first patients diagnosed with the syndrome, shared his perspective: “When my daughter was finally diagnosed after years of testing, it became our mission to build a supportive community dedicated to advancing understanding and treatment options for this disorder. This clinical trial represents a profound moment for our community, and we are hopeful for the future of our children and rare disease research.”
The Phase 2 study will enroll 30 participants aged 9-45 with a confirmed diagnosis of PPP2R5D-related neurodevelopmental disorder. Participants will receive a weight-adjusted dose of zatolmilast or placebo twice daily during a 24-week double-blind period, followed by an optional 24-week open-label extension. The trial is expected to conclude in late 2026, with additional details available on ClinicalTrials.gov (ID: NCT06717438).
Jordan’s Syndrome is characterized by a range of symptoms, including global developmental delays, seizures, vision problems, muscle weakness, attention disorders, and social and sensory challenges often associated with autism. The severity and presentation of symptoms vary widely among individuals, making diagnosis and treatment particularly challenging. Currently, there are no specific medications or curative treatments for the condition.
Diagnosing Jordan’s Syndrome requires whole-exome sequencing or diagnostic testing to identify mutations in the PPP2R5D gene, a process that is often inaccessible to many families. While approximately 350 individuals have been diagnosed globally, it is estimated that many more cases remain undiagnosed due to the syndrome’s overlap with other developmental disorders like autism spectrum disorder.
Dr. Wendy Chung, Chief of Pediatrics at Boston Children’s Hospital and lead principal investigator of the study, emphasized the significance of this milestone: “This trial represents the next step in our journey to develop a treatment for Jordan’s Syndrome. It would not have been possible without the collaboration of our research teams, the dedication of affected families, and our partnership with Shionogi, a company with a proven track record of scientific innovation.”
Preclinical research led by Dr. Stefan Strack at the University of Iowa demonstrated zatolmilast’s potential to improve cognitive function and address underlying disease processes in animal models of Jordan’s Syndrome, paving the way for this Phase 2 study.
Dr. Juan Carlos Gomez, Chief Medical Officer of Shionogi, expressed the company’s commitment to this initiative: “Shionogi is honored to partner with Jordan’s Guardian Angels on this historic study. Through the expansion of our zatolmilast clinical program, we aim to bring meaningful advances to the Jordan’s Syndrome community and uphold our mission to deliver breakthroughs for patients worldwide.”
The U.S. Food and Drug Administration (FDA) has granted zatolmilast Rare Pediatric Disease Designation (RPD) for the treatment of Jordan’s Syndrome, recognizing the urgent need for therapies for this serious and life-threatening condition that primarily affects children.
Commentary by SuppBase columnist Alice Winters
The announcement of the Phase 2 clinical trial for zatolmilast in Jordan’s Syndrome represents a beacon of hope for families affected by this ultra-rare genetic disorder. The collaboration between Shionogi, Jordan’s Guardian Angels, and a consortium of leading research institutions underscores the power of collective effort in addressing unmet medical needs.
From a scientific perspective, zatolmilast’s mechanism of action as a selective PDE4D inhibitor is particularly intriguing. PDE4D inhibitors have shown promise in modulating cognitive function and neurodevelopment, making them a compelling candidate for disorders like Jordan’s Syndrome and Fragile X syndrome. The drug’s dual focus on these conditions highlights its potential versatility in addressing a range of neurodevelopmental challenges.
However, the road ahead is not without challenges. The ultra-rare nature of Jordan’s Syndrome means that patient recruitment for clinical trials will be inherently difficult. Additionally, the variability in symptom presentation and severity complicates the assessment of efficacy. The inclusion of biomarker data in this study is a commendable approach, as it may provide deeper insights into the drug’s impact on underlying disease processes.
The involvement of Jordan’s Guardian Angels in driving this research forward is a testament to the critical role patient advocacy groups play in rare disease research. Their efforts to raise awareness, secure funding, and foster collaboration have been instrumental in bringing this trial to fruition.
While the trial’s results are still years away, the Rare Pediatric Disease Designation granted by the FDA is a significant regulatory milestone that could expedite the development and approval process. This designation not only underscores the urgency of addressing Jordan’s Syndrome but also highlights the broader need for innovative therapies in the rare disease space.
In conclusion, this clinical trial represents a pivotal step forward in the quest to improve the lives of individuals with Jordan’s Syndrome. It also serves as a reminder of the importance of sustained investment in rare disease research and the transformative impact of collaborative efforts between industry, academia, and patient advocacy groups. As we await the outcomes of this study, the hope it brings to the Jordan’s Syndrome community is immeasurable.
