CHAPLE disease (complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy) was first discovered in 2016 by researchers at the National Institute of Allergy and Infectious Diseases (NIAID). The disease leads to a deficiency in the complement protein CD55 – which normally helps control the body’s defense response to infections, injuries, or other threats. Without enough of that protein, the body’s defense mechanisms turn against its own healthy tissues instead of invaders.

CHAPLE disease causes people to lose protein in their gut, which can lead to life-threatening complications like thrombosis and severe gastrointestinal problems. It can cause frequent and dangerous nausea and vomiting, malnourishment, and infections. In one case, a 15-year-old from Bolivia suffered several of those symptoms and was stricken with frequent lung infections.

Most people diagnosed with CHAPLE disease are children, who face severely debilitating symptoms and life-threatening complications that begin in infancy. 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. From there, the researchers were able to develop a treatment for patients with CHAPLE disease.

After the initial discovery of CHAPLE disease, NIAID researchers filed a patent application in 2017 for a method of diagnosing and treating it. After positive test results from off-label use of eculizumab in 16 people with CHAPLE disease, they initiated a Cooperative Research and Development Agreement (CRADA) to develop the technology. In 2020, NIAID entered a 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 disease.

The CRADA was extensively negotiated and went through numerous revisions and three subsequent amendments. Funding was secured under the CRADA to conduct a multi-site, 110-week Phase II/III trial examining the Regeneron compound in patients with CHAPLE disease. 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.

In August 2023, Veopoz® (pozelimab-bbfg) became the first FDA-approved treatment for CHAPLE disease. The NIAID team hopes that pozelimab’s discovery and development could be a model for future discoveries that might offer hope to the 25 to 30 million Americans who suffer from rare diseases.

And that teenager from Bolivia? He had his travel coordinated to the United States to participate in the trial at the NIH Clinical Center. Now, he is symptom-free and enjoying a life of normal eating and activities for the first time. A true, inspirational tech transfer success!

This technology received a 2025 FLC Impact Award.