Massimo Radaelli is a lifelong serial entrepreneur in the global pharmaceutical and biotech industries, with a particular focus on rare diseases.
First of all, congratulations on the awards. What pleases you most about this recognition?
I am extremely honoured to have been recognised by European CEO as “2024 CEO of the Year in the Pharmaceutical Industry,” and to have recently been named “Best European Biopharmaceutical Innovator CEO of the Year – 2024” by the magazine The European.
I believe this new award 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.
Please underline the importance of research in rare diseases, and why are they called orphan drugs?
While individual rare diseases might impact a small fraction of the global population, they are collectively a public health priority. There is increasing awareness about rare diseases and their diagnoses: roughly 8,000 have been identified, yielding a prevalence rate of 3.5 percent to 5.9 percent. Rare diseases affect an estimated 260-440 million people worldwide, and 70 percent of rare diseases exclusively start in childhood.
Innovations such as gene therapies, personalised medicines, and precision medicine approaches are gaining momentum in the field of rare disease treatment. In particular, the rise of orphan drugs has revolutionised the treatment landscape for rare diseases, offering new hope and possibilities to individuals and families affected by these often devastating and debilitating conditions.
An orphan drug is defined as a pharmaceutical agent developed specifically to treat rare diseases. The rarity of these diseases often results in limited commercial viability for drug developers, hence the term “orphan” drugs.
Please describe your position and activities and the company’s strategy
I’m the President and CEO of Napo Therapeutics and a board member of the company, and I am the President of Jaguar Health International. Napo Therapeutics is an independent European pharmaceutical company headquartered in Milan, Italy. Thanks to its partnership and license agreement with San Francisco, California-based Jaguar Health, Napo Therapeutics can benefit from the Jaguar leadership team’s decades of experience in plant-based prescription medicines and the strong international supply chain Jaguar has in place for crofelemer, its novel plant-based prescription drug product. Together, the aim of Napo Therapeutics and Jaguar is to improve the quality of life of people suffering from gastrointestinal rare diseases with high unmet needs through innovative solutions.
Can you explain in more detail what type of product crofelemer is and what are its potential therapeutic follow-on indications?
Crofelemer is the first FDA-approved oral botanical drug. It is a novel, first-in-class anti-secretory antidiarrheal drug that has a normalising effect on electrolyte and fluid balance in the gut, and this mechanism of action has the potential to benefit multiple disorders that cause gastrointestinal distress.
Crofelemer is purified from the red bark sap, also referred to as “dragon’s blood,” of the Croton lechleri tree in the Amazon Rainforest. Jaguar has established a sustainable harvesting programme, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for indigenous communities.
Crofelemer is a pipeline within a product with multiple potential follow-on indications, including cancer therapy-related diarrhea (CTD); intestinal failure due to the rare diseases microvillus inclusion disease (MVID) and short bowel syndrome (SBS-IF); diarrhea-predominant irritable bowel syndrome (IBS-D); and chronic idiopathic/functional diarrhea.
Please describe the objectives of the current rare disease-focused clinical trials
The most advanced programme of Napo Therapeutics is MVID. There are no approved drug treatments for this devastating disease. MVID is an ultrarare pediatric congenital diarrheal disorder (CDD) characterised by severe diarrhea and malabsorption that requires intensive parenteral support for nutritional and fluid management including total parenteral nutrition (TPN) – and TPN carries the risk of morbidity, infections, metabolic complications, liver and kidney problems, and neurodevelopmental delay.
Our other rare disease programme is for short bowel syndrome with intestinal failure (SBS-IF): A condition in which the body is unable to absorb enough nutrients from the foods the patients eat because the individual does not have enough small intestine.
MVID and SBS-IF patients suffer from malnutrition, dehydration, imbalances of fluids and salts, excessive intestinal fluid output, and risk of organ failure.
Crofelemer is the first FDA-approved oral botanical drug
The initial results of an ongoing investigator-initiated (IIT) proof-of-concept trial of a novel liquid formulation of crofelemer in Abu Dhabi in the United Arab Emirates 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.
These initial results were presented on April 26, 2025 at the Annual ELITE PED-GI Congress by Dr. Mohamad Miqdady, a recognised leader in pediatric gastroenterology who serves as the Chief of Pediatric Gastroenterology, Hepatology and Nutrition at Sheikh Khalifa Medical City in Abu Dhabi. He is the Principal Investigator for this ongoing exploratory, single-arm open label non-randomised study, and he is a member of the Scientific Advisory Board of Jaguar family company Napo Pharmaceuticals.
As announced in June 2025, initial proof-of-concept results from the ongoing trial in Abu Dhabi show that crofelemer reduced the required total parenteral nutrition (TPN) and supplementary intravenous fluids in a third pediatric intestinal failure patient – a patient with SBS-IF.
Because MVID is so rare, initial results in a very small number of MVID patients showing benefit with crofelemer may allow us to explore pathways for expedited regulatory approval in the European Union for this indication. Crofelemer may qualify for participation in the European Medicines Agency’s PRIME programme for expediated and assisted regulatory approval in the EU and in the FDA’s Breakthrough Therapy programme for expedited regulatory approval in the US.
Crofelemer is the subject of four clinical efforts for MVID and SBS-IF in the US, EU, and Middle East regions: two proof-of-concept (POC) IITs and two placebo-controlled Phase 2 studies that Napo Therapeutics and I are managing. Additional POC results from IITs are expected throughout 2025.
Please tell us about the recently conducted Phase 3 OnTarget trial of crofelemer for cancer therapy-related (CTD)
OnTarget was a global Phase 3 prophylactic clinical trial of crofelemer conducted by Jaguar family company Napo Pharmaceuticals for diarrhea in adult patients with solid tumors receiving targeted therapy with or without standard chemotherapy. While the initial top line results from the study showed that this multicentre, double-blind, placebo-controlled pivotal trial did not meet its primary endpoint for the prespecified analysis of all tumor types, the subgroup analysis in adult breast cancer patients indicates that crofelemer achieved significant results in this subgroup. Patients with breast cancer accounted for 183 of the 287 participants in this study.
The results in breast cancer patients were the subject of a poster presentation on December 11, 2024, at the San Antonio Breast Cancer Symposium, and additional significant results in adult breast cancer patients from the OnTarget study were the subject of an oral rapid e-poster at the Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting in June 2025 in Seattle, Washington.
Napo Pharmaceuticals participated in an in-person Type C Meeting on May 28, 2025 with the Division of Gastroenterology of the FDA to discuss the statistically significant responder analysis results for adult patients with breast cancer in the OnTarget trial. Napo Pharmaceuticals proposed two simultaneous potential pathways during the meeting for making crofelemer available to metastatic breast cancer patients with the significant unmet medical need of cancer therapy-related diarrhea (CTD): conducting a pivotal treatment trial to facilitate approval of crofelemer for CTD in this focused patient population; and the prompt pursuit of authorisation to initiate an expanded access program for breast cancer patients with CTD who may not be eligible for this study, including breast cancer patients in the adjuvant and neoadjuvant settings. The FDA formally acknowledged both of these key discussion points in correspondence to Napo Pharmaceuticals, and Napo Pharmaceuticals plans to submit a protocol to the FDA for a pivotal treatment trial for a smaller number of metastatic breast cancer patients using crofelemer.
The rise of orphan drugs has revolutionised the treatment landscape for rare diseases
The currently estimated US metastatic breast cancer population potentially qualifies as an orphan population, in alignment with Jaguar’s core focus on orphan diseases. Jaguar therefore intends to request orphan drug designation from the FDA for the CTD indication in this population. Given crofelemer’s novel and paradigm-shifting mechanism of action, the company also plans to seek Breakthrough Therapy designation and/or Fast Track designation from the FDA to support potentially expedited regulatory approval in the US for crofelemer for CTD in metastatic breast cancer patients.
Diarrhea is a common side effect of targeted cancer therapies and can lead to dose changes, treatment delays, or cessation of treatment altogether, all of which can impact patient outcomes. In this responder analysis of OnTarget patients with breast cancer on targeted therapies, crofelemer prophylaxis resulted in a greater proportion of monthly responders of diarrhea improvement compared to placebo. Overall, crofelemer was significantly more effective than placebo in providing sustained response in breast cancer patients.
To conclude our interview please indicate the key aspects of a CEO’s role in the pharma sector today and summarise in a few words what qualities a CEO must possess
A CEO, in addition to being a team player, must facilitate the interaction of his or her company’s employees. A CEO must be very well prepared for the field on which their team is playing. Critical qualities for a CEO are emotional intelligence, compassion, and the ability to inspire greatness in employees. However, the most important and indispensable quality required to be an effective CEO: an ethical outlook.