THE PROBLEM: In 2016, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) were the first to identify an extremely rare genetic disorder leading to a deficiency in the complement protein CD55, which normally helps control the body’s defense response to infections, injuries, or other threats. People with CHAPLE (which stands for complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy) disease have two defective copies of the CD55 gene, and the defense mechanisms in the body attack its own healthy tissues instead of invaders, leading to an entirely new cascade of life-threatening health problems. 

THE SOLUTION: The NIAID team observed promising test results using eculizumab, a Food and Drug Administration (FDA)-approved treatment for a different genetic disease in the same spectrum. Then, the NIAID team used those results to develop a treatment for patients with CHAPLE disease. In 2020, NIAID entered a Cooperative Research and Development Agreement (CRADA) with Regeneron to study the safety and efficacy of Regeneron’s proprietary compound pozelimab in a Phase II/III trial in people with CHAPLE. In August 2023, Veopoz (pozelimab-bbfg) became the first FDA-approved treatment for CHAPLE disease. 

THE TECH TRANSFER MECHANISM: After the initial discovery, NIAID researchers filed a patent application in 2017 for a method of diagnosing and treating CHAPLE disease. They collaborated to investigate the off-label use of eculizumab in 16 people with CHAPLE disease and, when positive test results were becoming clear, they initiated a CRADA to develop the technology. The diligent, meticulous work of the technology transfer team was instrumental in the success of the smooth and timely execution of the extensively negotiated CRADA, its numerous revisions, and three subsequent amendments. In 2020, funding was secured under the CRADA to conduct a multi-site, 110-week Phase II/III trial examining the Regeneron compound in a patient with CHAPLE disease at the NIH Clinical Center. After the trial was successfully completed, Regeneron filed a biologics license application with the FDA, which was accepted for priority review, given the significance of its anticipated impact on patient care. 

THE IMPACT: Most people diagnosed with CHAPLE disease are children who face severely debilitating symptoms and life-threatening complications that begin in infancy. In one case, a 15-year-old from Bolivia suffered severe gastrointestinal pain, nausea and vomiting, malnourishment, and frequent lung infections. Team members at the NIH Clinical Center coordinated his travel to the United States for the trial, and he is now symptom-free, enjoying a life of normal eating and activities for the first time. In broader terms, pozelimab’s discovery and development could be a model for future discoveries that could offer hope to the 25 to 30 million Americans who suffer from rare diseases.