FDA Grants Orphan-Drug Status to Jaguar's Crofelemer for Cholera Diarrhea Treatment

Cholera, a severe diarrheal disease caused by Vibrio cholerae, remains a significant global health challenge. According to the World Health Organization (WHO), cholera outbreaks have been classified at the highest emergency level due to their global resurgence. The disease affects millions annually, with estimates ranging from 1.3 to 4 million cases and 21,000 to 143,000 deaths worldwide. Cholera is characterized by acute watery diarrhea, vomiting, and severe dehydration, potentially leading to death if untreated.

In a recent development, Jaguar Health's subsidiary, Napo Pharmaceuticals, announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation (ODD) to crofelemer for the treatment of diarrhea associated with cholera. Crofelemer, a plant-based drug, offers a novel approach to managing this life-threatening condition. This designation recognizes the drug's potential to address an unmet medical need, especially in the context of its rare occurrence in the United States, where cholera is considered an orphan disease.

The orphan-drug designation provides several incentives for further development and potential commercialization. These include tax credits for clinical trials, exemption from certain regulatory fees, and a period of market exclusivity upon approval. Jaguar Health aims to secure similar designation from the European Medicines Agency (EMA) to facilitate the drug's availability in Europe.

Crofelemer is not only being explored for cholera but also for other rare conditions such as short bowel syndrome with intestinal failure (SBS-IF) and microvillus inclusion disease (MVID). Five clinical studies, including investigator-initiated trials and Phase 2 studies, are underway to evaluate its efficacy in these diseases across different regions, including the United States, Europe, and the Middle East/North Africa. Initial dosing in these trials is anticipated between December 2024 and the first quarter of 2025, with preliminary results expected by mid-2025.

The pursuit of orphan-drug designation underscores the importance of crofelemer in addressing significant health challenges. Additionally, Jaguar Health is exploring the use of NP-300, another plant-derived compound, for cholera treatment. They aim to obtain a Tropical Disease Priority Review Voucher from the FDA, which could significantly expedite the drug's review process and provide substantial financial returns.

While cholera remains a rare disease in the U.S., its global impact is vast. The Centers for Disease Control and Prevention (CDC) reports that about 10% of infected individuals experience severe symptoms, leading to rapid dehydration and shock. Prompt medical intervention is critical to prevent fatalities. Cholera is endemic in many parts of the world, and recent data from WHO highlight its widespread occurrence, with over 300,000 cases and more than 2,300 deaths reported across multiple countries in just the first half of 2024.

The WHO continues to assess the global cholera risk as very high, exacerbated by outbreaks, geographical spread, and limited vaccine supplies. This sustained threat necessitates innovative treatments like crofelemer to complement preventive measures and improve patient outcomes.

Jaguar Health, through its subsidiaries, is committed to developing sustainable, plant-based pharmaceuticals for gastrointestinal disorders. Their efforts in making crofelemer accessible for rare diseases reflect a broader mission to address neglected health conditions through eco-friendly solutions. With ongoing research and regulatory efforts, crofelemer represents a promising therapy for those impacted by cholera and other severe gastrointestinal diseases.