A revolutionary therapeutic, derived from the sap of an Amazonian rainforest tree, is showing significant promise as a potential treatment for rare and life-threatening intestinal failure conditions, offering a beacon of hope to patients and families navigating these complex medical challenges. Massimo Radaelli, President & CEO of Napo Therapeutics, shared insights into the development and potential impact of crofelemer, a plant-based drug poised to disrupt the landscape of gastrointestinal rare disease treatment.
Radaelli, a seasoned pharmaceutical executive with over three and a half decades dedicated to the innovation of therapies for rare diseases, leads Napo Therapeutics, an Italian company established in 2021 by California-based Jaguar Health. The company’s primary mission is to develop and commercialise crofelemer in Europe, with a strategic focus on rare gastroenterological disorders. His extensive experience and commitment to this field underscore the significance of this emerging therapeutic avenue.
The recognition of Radaelli’s work, including a recent Global CEO Excellence Award, highlights a lifelong dedication to advancing orphan medicines. This acknowledgement, he states, "recognises once more, at an international level, my lifelong commitment to the research and development of orphan medicines for the treatment of patients with rare diseases." This international validation signals a growing awareness and appreciation for the critical need to address conditions that affect a limited patient population but carry immense debilitating consequences.
Intestinal failure represents a particularly devastating medical condition, often necessitating patients, including infants and young children, to rely on life-sustaining intravenous administration of fluids, electrolytes, and nutrients. This regimen, known as total parenteral nutrition (TPN) combined with supplemental intravenous fluids, constitutes parenteral support. For many, this intensive treatment is a daily necessity, sometimes requiring up to 20 hours per day, seven days a week. While indispensable for survival, parenteral support is fraught with significant toxicities, mirroring some of the severe side effects associated with chemotherapy. These can manifest as life-altering health problems, including chronic infections, complex metabolic derangements, and damage to vital organs like the liver and kidneys. The long-term implications of such intensive treatment regimes place an immense burden on patients and healthcare systems alike.
The medical community has long sought effective treatments for intestinal failure, particularly for conditions like microvillus inclusion disease (MVID) and short bowel syndrome with intestinal failure (SBS-IF). Currently, MVID has no approved therapies. For SBS-IF, treatment options are limited, with teduglutide and GLP-2 analogs offering some relief to a subset of patients. Napo Therapeutics, in collaboration with Jaguar Health and its sister company Napo Pharmaceuticals, is advancing crofelemer, a first-in-class oral medication with demonstrated clinical proof-of-concept in these specific orphan indications. Radaelli explained that by potentially reducing the reliance on parenteral support, crofelemer could fundamentally alter the prognosis for MVID and SBS-IF patients, offering them a chance at a longer and potentially less burdened life. The current natural history of requiring prolonged parenteral support is associated with significant mortality risks, making any therapeutic that can mitigate this dependency a critical development.
Significant progress is being made in the clinical and business development of crofelemer for these rare diseases. An independent proof-of-concept study in pediatric intestinal failure patients is currently underway in the United Arab Emirates. The preliminary findings, presented in November 2025 at the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Annual Meeting, are highly encouraging. Patients in the study have now been receiving crofelemer for over a year, and the initial results indicate a modification of disease progression through a reduction in the required volume of parenteral support, ranging from a notable 12% to 37%.
Building on these positive outcomes, Jaguar Health’s ongoing pivotal placebo-controlled trial of crofelemer in pediatric MVID patients is anticipated to conclude in the second quarter of 2026. Given the ultra-rare nature of MVID and the absence of any approved treatments, the company is actively pursuing Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA). This designation would significantly accelerate the regulatory pathway to market in the United States. Simultaneously, Napo Therapeutics aims to qualify crofelemer for the European Medicines Agency’s (EMA) PRIME (priority medicines) programme, a critical step towards expediting approval within the European Union.
The strategic approach to bringing crofelemer to market involves seeking partnerships for development and commercialisation. Napo Therapeutics is actively exploring global or regional collaborations, including potential licensing agreements, co-promotion opportunities, or strategic product acquisition deals. The immediate focus for value generation is on MVID, owing to the potential for accelerated regulatory pathways. The estimated global prevalence of MVID is approximately 200 patients, meaning that a trial involving even a small cohort can yield statistically significant results to support regulatory approval. SBS-IF, the focus of an ongoing Phase two trial for crofelemer, represents a more substantial follow-on market opportunity, with an estimated patient population of around 12,000 in the United States alone.
The development pathway for botanical drugs like crofelemer offers distinct advantages. Crofelemer is sustainably sourced from the red bark sap of the Croton lechleri tree, a fast-growing species indigenous to the tropical forests of Colombia, Ecuador, Peru, and Bolivia. This sap has a rich history of traditional medicinal use by indigenous communities, providing a foundation of empirical knowledge. Crofelemer is the active compound in Mytesi, Jaguar Health’s FDA-approved prescription drug for the symptomatic relief of non-infectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. Mytesi holds the distinction of being the only oral product approved under the FDA’s Botanical Guidance.
This botanical drug development framework offers a unique form of intellectual property protection. Instead of protecting a specific chemical molecule, it safeguards the entire integrated manufacturing and quality control system that ensures the consistent delivery of the approved botanical drug product to patients. This comprehensive approach effectively creates a barrier to generic competition, as replicating the entire complex system is practically infeasible.
Furthermore, the established history of human exposure to botanical compounds can provide a pre-existing safety profile. This can lead to Investigational New Drug (IND) applications for botanical drugs having a lower probability of the late-stage safety failures that frequently lead to the termination of conventional New Chemical Entity (NCE) programs. This inherent characteristic effectively de-risks the clinical development process, potentially leading to more efficient and successful trials. The fusion of ancient botanical knowledge with cutting-edge scientific research and rigorous clinical development is paving the way for transformative treatments for some of the world’s most challenging rare diseases.
