Reforested Croton lechleri tree in the Amazon, near Iquitos, Peru © Steven King 
Interview with: Massimo Radaelli, President & CEO, Napo Therapeutics
Massimo Radaelli, PhD, is a European pharmaceutical industry leader and entrepreneur who has devoted more than 30 years to the innovation of therapies to treat rare diseases. He is President and CEO of Napo Therapeutics, a pharmaceutical company established in Milan, Italy, in 2021 by California-based Jaguar Health to develop and commercialise the plant-based drug crofelemer in Europe, with a particular focus on rare gastroenterological diseases. Radaelli explained to World Finance why a drug sustainably derived from an Amazon Rainforest tree may provide a novel therapeutic option for patients with intestinal failure due to microvillus inclusion disease and short bowel syndrome.
First of all, congratulations on your recent awards. What pleases you most about the recognition?
I am extremely honoured to have been recognised by European CEO as ‘2024 CEO of the Year in the Pharmaceutical Industry,’ and also to have been named ‘Best European Bio-pharmaceutical Innovator CEO of the Year 2024’ by The European. I believe this latest award – from European CEO (sister brand of World Finance) – recognises once more, at an international level, my lifelong commitment to the research and development of orphan medicines for the care and therapy of patients with rare diseases. I am grateful both for the recognition and to have been able to spend decades focused on helping patients suffering from rare diseases around the world.
Can you tell us about intestinal failure?
Intestinal failure is a condition where the intestines cannot adequately absorb the necessary water, macronutrients – carbohydrates, protein and fat – micronutrients, and electrolytes sufficient to sustain life. Patients with intestinal failure due to the rare diseases microvillus inclusion disease (MVID) and short bowel syndrome (SBS-IF) suffer from devastating diarrhea and dehydration caused by these debilitating, lifelong conditions and often require total parenteral nutrition (TPN) up to seven days a week for more than 12 hours a day.
The Croton lechleri sap…has a long history of medicinal use by indigenous peoples
TPN is a medical feeding method where nutrients are delivered directly into a vein through an IV line, bypassing the digestive system, and chronic TPN use carries the risk of morbidity, infections, metabolic complications, liver and kidney problems and neurodevelopmental delay. Limited therapeutic options exist for SBS-IF beyond TPN, and there are no approved drug treatments for MVID.
MVID and SBS-IF are devastating, lifelong conditions. The biggest impact one can have on a patient with intestinal failure is reduction in the quantity and time of TPN. We are always concerned about the quality of life of patients with MVID and SBS-IF, most of whom are children. They are not able to eat or drink and spend most of their waking hours hooked up to an IV.
Can you explain what type of product crofelemer is, and why it may provide a novel therapeutic option for patients with intestinal failure due to MVID and SBS-IF?
Crofelemer is a plant-based drug sustainably derived from the red bark sap of the Croton lechleri tree – a rapidly growing tree species common in tropical forests of Colombia, Ecuador, Peru and Bolivia. The Croton lechleri sap, commonly known as sangre de drago – which translates to ‘dragon’s blood’ in Spanish – has a long history of medicinal use by indigenous peoples. Crofelemer works by reducing chloride ion secretion into the gut lumen and normalising the electrolyte and fluid balance. It is the active ingredient in Jaguar Health’s FDA-approved prescription drug for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy, and in Jaguar Health’s FDA conditionally approved prescription drug for treatment of chemotherapy-induced diarrhea in dogs. As announced in April, the initial results of an ongoing investigator-initiated proof-of-concept trial of a novel liquid formulation of crofelemer in the UAE show that crofelemer reduced the required TPN and/or supplementary intravenous fluids – collectively referred to as parenteral support – in pediatric patients with intestinal failure due to MVID and short bowel syndrome by up to 27 percent and 12.5 percent respectively. This data also showed crofelemer reduced stool volume output and/or frequency of watery stools, and increased urine output – an indicator of improved nutrient oral absorption.
We are very excited about these initial results. While short bowel syndrome affects approximately 10,000 to 20,000 people in Europe and roughly the same number in the US, MVID is an ultra-rare condition – with an estimated prevalence of just a couple of hundred patients globally. Given this situation, initial results in a very small number of MVID patients showing benefit with crofelemer may allow us to explore pathways for expedited regulatory approval for this indication, including the European Medicines Agency’s PRIME programme and the FDA’s Breakthrough Therapy programme.
Crofelemer is currently the subject of five clinical efforts for MVID and SBS-IF in the US, EU and Middle East regions – two placebo-controlled Phase two studies that Napo Therapeutics is managing, and three investigator-initiated trials. Additional proof-of-concept results from investigator-initiated trials are expected throughout 2025.
