Crofelemer Receives FDA Orphan Drug Designation for Cholera-Related Diarrhea
Key Insights
The FDA has granted orphan-drug designation to crofelemer for treating diarrhea (search) in cholera (search), a rare condition in the U.S.
This designation provides Jaguar Health with development incentives, including tax credits and marketing exclusivity.
Crofelemer is also being investigated for short bowel syndrome (search) and microvillus inclusion disease (search), with potential EU access.
Jaguar Health's family company, Napo Pharmaceuticals (search), has received orphan-drug designation (ODD) from the U.S. Food and Drug Administration (FDA) for crofelemer, a plant-based prescription drug, to treat diarrhea (search) in cholera (search). This regulatory decision aims to address a critical unmet need, particularly in regions where cholera remains a significant public health concern.
Steven King, PhD, Jaguar’s Chief Sustainable Supply, Ethnobotanical Research & IP Officer, stated, “We are very pleased that crofelemer has been granted orphan-drug designation for this important indication.” He also noted the company's previous presentation of Phase 2 data on crofelemer for treating dehydration in cholera (search) patients at the International Centre for Diarrhoeal Disease Research (icddr,b) in Bangladesh.
Clinical Significance and Global Impact
Cholera (search), caused by the bacterium Vibrio cholerae, results in acute diarrheal illness and severe dehydration. According to the Centers for Disease Control and Prevention (CDC), approximately 1 in 10 infected individuals develop severe symptoms, leading to potentially fatal dehydration and shock if left untreated. While rare in the United States, cholera affects 1.3 to 4 million people globally each year, resulting in 21,000 to 143,000 deaths.
The World Health Organization (WHO) has classified the global resurgence of cholera (search) as a grade 3 emergency, its highest internal level. From January to July 2024, 307,433 cases and 2,326 deaths were reported across 26 countries.
Development Incentives and Regulatory Pathway
The FDA's orphan-drug designation provides Jaguar Health with several development incentives, including tax credits for clinical testing, waived filing fees, and a seven-year period of market exclusivity in the U.S. if crofelemer is approved for this indication. Jaguar Health intends to pursue a similar designation from the European Medicines Agency (EMA).
Ongoing Clinical Efforts
Crofelemer is currently under investigation in five other rare disease-related clinical efforts, including three investigator-initiated trials (IITs) and two Phase 2 studies for short bowel syndrome (search) with intestinal failure (SBS-IF) and microvillus inclusion disease (search) (MVID) across the U.S., European Union, and Middle East/North Africa regions. Dosing of the first patient in each of these five studies is expected to occur throughout December 2024 and Q1 2025, with availability of IIT proof-of-concept results potentially in Q2 2025.
Additional Therapeutic Strategies
Jaguar Health is also planning to pursue orphan-drug designation and a Tropical Disease Priority Review Voucher for NP-300, a second-generation anti-secretory agent, for treating diarrhea (search) in cholera (search). Like crofelemer, NP-300 is derived from the Croton lechleri tree. Priority review vouchers are transferable and have been sold for significant values in past transactions, potentially providing a substantial return on investment upon approval.