Jaguar Health has announced that its subsidiary Napo Pharmaceuticals submitted an orphan drug designation (ODD) application to the U.S. Food and Drug Administration for crofelemer, targeting diarrhea treatment in adult patients with breast cancer that has metastasized to the brain receiving targeted therapy with or without standard chemotherapy.
FDA Recognition of Distinct Orphan Condition
The FDA's Office of Orphan Products Development has publicly acknowledged that brain metastasis of any cancer is considered a disease or condition separate and distinct from the primary site of origin. This recognition has led to significant regulatory precedent, with the OOPD awarding seven orphan drug designations for various therapies for the treatment of breast cancer that has metastasized to the brain between 2015 and 2024.
"The FDA has identified the condition of breast cancer that has metastasized to the brain as an orphan indication. We have submitted this ODD application for crofelemer to treat diarrhea in these patients," said Lisa Conte, Jaguar's founder, president, and CEO.
Clinical Significance and Treatment Impact
Diarrhea represents a common side effect of numerous targeted cancer therapies that can lead to dose changes, treatment delays, or cessation of treatment altogether, all of which impact patient outcomes. The company's application addresses this significant clinical challenge in a vulnerable patient population.
Given crofelemer's novel and physiological mechanism of action, Jaguar plans to seek Breakthrough Therapy designation and/or Fast Track designation from the FDA to support potentially expedited regulatory pathways in the U.S. for this indication.
Crofelemer's Regulatory History
Crofelemer has established a strong regulatory foundation with previous orphan drug designations. In both the US and European Union, crofelemer has received orphan drug designation for short bowel syndrome with intestinal failure and microvillus inclusion disease for a liquid formulation. The drug has also been granted orphan drug designation for treatment of diarrhea in cholera in the U.S.
Drug Development and Sourcing
Crofelemer is a botanical drug extracted and purified from the red bark sap, also referred to as "dragon's blood," of the medicinal Croton lechleri tree in the Amazon Rainforest. Napo Pharmaceuticals has established a sustainable harvesting program under fair trade practices for crofelemer to ensure quality, ecological integrity, and support for indigenous communities.
Regulatory Benefits
Orphan drug designation qualifies the drug sponsor for various development and regulatory incentives, including tax credits for qualified clinical testing and relief from filing fees. Furthermore, orphan drug designation in the U.S. provides a seven-year period of marketing exclusivity to the first sponsor.
The potential treatment for patients with breast cancer with metastasis to the brain with crofelemer would augment the significant responder analysis results for crofelemer in the prespecified subgroup of patients with breast cancer from the OnTarget study that were reported at the Multinational Association of Supportive Care in Cancer 2025 Annual Meeting and the 2024 San Antonio Breast Cancer Symposium.
