A Phase 2, Placebo-Controlled, Randomized, Double-Blind Study of 2 Doses of Crofelemer for the Treatment of Adult Patients With Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC)

A 24-week, randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety and tolerability of crofelemer in patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF) without colon-in-continuity (CIC) requiring parenteral support (PS).
Blinded study drug will be administered orally (or enterally) three times daily (TID) as a novel crofelemer formulation, Crofelemer Powder for Oral Solution, or a matching placebo powder formulation for oral solution.
Patients will be randomized in a 1:1:1 ratio to crofelemer 3 mg/kg/dose TID, crofelemer 10 mg/kg/dose TID or placebo and randomization will be stratified by baseline PS volume (≤4 or >4 L/week).

Start Date29 May 2025

Sponsor / Collaborator

Napo Therapeutics SpA

NCT06721871

/ RecruitingPhase 2

Evaluation of Safety, Tolerability and Efficacy of Crofelemer Following Multiple Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Participants With Microvillus Inclusion Disease (MVID)

a 32-week study that will evaluate the safety, tolerability and preliminary efficacy of multiple ascending doses of crofelemer, compared to placebo, using a randomized cross-over design within each dose level, when administered to participants with MVID receiving parenteral support (PS, defined as TPN with or without supplementary IV fluid requirements). Blinded study drug will be administered as a novel crofelemer formulation, Crofelemer Powder for Oral Solution, or a matching placebo powder formulation for oral solution. Assigned study drug will be reconstituted and administered orally (or enterally) three times daily (TID) as a concentrated liquid formulation in each of the three dose levels

Start Date01 May 2025

Sponsor / Collaborator

Napo Pharmaceuticals, Inc.

NCT06326645

/ RecruitingEarly Phase 1IIT

Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome

The objectives of this study are to evaluate the efficacy and safety of crofelemer treatment in adults affected by Short Bowel Syndrome (SBS) with an ileostomy on parenteral support (PS) in reducing output or PS needs. Crofelemer will be provided as a powder three times daily for 12 weeks and a 4 week follow up. .

Start Date03 Mar 2025

Sponsor / Collaborator

The Cleveland Clinic Foundation

[+1]

100 Clinical Results associated with Crofelemer

100 Translational Medicine associated with Crofelemer

100 Patents (Medical) associated with Crofelemer

Literatures (Medical) associated with Crofelemer

01 Apr 2024·American journal of medical genetics. Part A

Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant

Author: Horton, Darlene ; Teng, Ru-Jeng ; Wong, Ian Guo Yi ; Scott, William ; Muriello, Michael ; Cramer, Jesse ; Basel, Donald ; Elkadri, Abdul

Abstract:

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate‐cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate‐cyclase 2C (GC‐C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology‐driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC‐C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi‐disciplinary family‐directed decision‐making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

16 Oct 2023·The Journal of clinical investigation

Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.

Article

Author: Kalashyan, Meri ; Thiagarajah, Jay R ; Bayer, Marie-Theres ; Roland, Joseph T ; Shub, Mitchell D ; Oller, Haley ; Kolobova, Elena ; Goldsmith, Jeffrey D ; Raghunathan, Krishnan ; Jimenez, Lissette ; Hagen, Susan J ; Kaji, Izumi ; Goldenring, James R

Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes. Multiplex immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking antidiarrheal drug crofelemer dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. γ-Secretase inhibition with DAPT recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum/glucocorticoid-regulated kinase 2 (SGK2) and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID.

01 Oct 2023·Clinical breast cancer

Crofelemer for the Management of Neratinib-Associated Diarrhea in Patients With HER2+ Early-Stage Breast Cancer.

Article

Author: Melisko, Michelle ; Quintal, Laura ; Rugo, Hope S ; Johnson, MacKenzie ; Jacob, Saya ; Chien, Amy Jo ; Roque, Brianna

BACKGROUND:

To evaluate the efficacy of crofelemer, a first in class anti-secretory anti-diarrheal agent, to manage neratinib-induced diarrhea in patients with early-stage breast cancer taking adjuvant neratinib.

PATIENTS AND METHODS:

This single center, open label trial enrolled patients with Stage 2 to 3 HER2+ breast cancer taking adjuvant neratinib. One cohort took prophylactic crofelemer 125 mg bid and loperamide in the first 2 cycles, and as needed in subsequent cycles. The second cohort took dose-escalated neratinib with loperamide as needed (DE cohort). The primary endpoint was incidence of grade ≥ 3 diarrhea in the first 2 cycles.

RESULTS:

Seven patients in the crofelemer cohort and 4 in the DE cohort were enrolled. In the first 2 cycles, 2 patients (29%) in the crofelemer cohort and 2 patients (50%) in the DE cohort experienced grade 3 diarrhea lasting 1 day on average. After cycle 2, no additional patients in either cohort had grade 3 diarrhea. Five of 7 patients controlled diarrhea with crofelemer alone. There were no grade 4 diarrhea events in either cohort. Three patients in the crofelemer cohort dose-reduced neratinib due to diarrhea in the first 2 cycles. Patients in the crofelemer cohort had an average of 0.58 diarrhea episodes/day. 82% experienced constipation, all grade 1.

CONCLUSIONS:

This is the first study to investigate crofelemer for neratinib-induced diarrhea and demonstrates crofelemer activity in this setting. Further investigation of crofelemer for diarrhea secondary to cancer treatment is needed.

280

News (Medical) associated with Crofelemer

11 Jun 2025

·jaguarhealth.gcs-web.com

First Study Site Established for Jaguar Health Study of its FDA Conditionally Approved Canalevia-CA1 Prescription Drug for Dogs

Two parallel goals for Canalevia-CA1 (crofelemer delayed-release tablets): To obtain full approval of the drug for treatment of chemotherapy-induced diarrhea (CID) and to expand the indication of crofelemer from CID to treatment of general, non-infectious diarrhea in dogs Jaguar in discussions with potential partners to license and fund development and commercialization of crofelemer for the treatment of general, non-infectious diarrhea in dogs in the U.S. and/or globally Diarrhea is one of the most common reasons for veterinary visits for dogs and the second most common reason for visits to the veterinary emergency room, yet there are currently no FDA-approved drugs to treat general diarrhea in dogs SAN FRANCISCO, CA / ACCESS Newswire / June 11, 2025 / Jaguar Health, Inc. (NASDAQ:JAGX) (Jaguar), under its Jaguar Animal Health tradename for the veterinary market, today announced that the first study site has been established for Jaguar's field study of Canalevia-CA1, Jaguar's U.S. Food and Drug Administration (FDA) conditionally approved prescription drug for the treatment of chemotherapy-induced diarrhea (CID) in dogs. Jaguar has two parallel goals for Canalevia-CA1 (crofelemer delayed-release tablets): To obtain full approval of the drug for treatment of chemotherapy-induced diarrhea (CID) in dogs and to expand the indication of crofelemer from CID in dogs to treatment of general, non-infectious diarrhea in dogs. The company is in discussions with potential partners to fund development and commercialization of crofelemer for the treatment of general, non-infectious diarrhea in dogs in the U.S. and/or globally. "We've been pleased with the marketplace reception of crofelemer for treatment of CID in dogs, and believe there is clearly an unmet medical need for a product for the much larger market of treatment of general, non-infectious diarrhea in dogs," said Lisa Conte , Jaguar's Founder and CEO. "We estimate that U.S. veterinarians see approximately six million annual cases of acute and chronic diarrhea in dogs, and we look forward to identifying a partner to fund and execute development and commercialization of crofelemer for the treatment of general, non-infectious diarrhea in the U.S and/or globally. Forging a partnership for this purpose is a key focus of our business development efforts in 2025 and has been designated as a key potential catalyst for the company this year." "Jaguar's canine-focused business development efforts align with our ongoing business development efforts on the ‘human' side of the company for crofelemer - the catalysts for which are the pathways discussed with the FDA to bring crofelemer to metastatic breast cancer patients, a population we feel meets the requirements for orphan drug status; and the prompt establishment of an expanded access program for crofelemer for the ongoing important unmet medical need of cancer therapy-related diarrhea in breast cancer patients; and the initial proof-of-concept results from the ongoing investigator-initiated trial (IIT) of a novel liquid formulation of crofelemer in Abu Dhabi in pediatric patients with intestinal failure due to the orphan diseases microvillus inclusion disease (MVID) and short bowel syndrome (SBS-IF). As recently announced, the initial proof-of-concept results of this IIT show crofelemer reduced the required total parenteral nutrition (TPN) and/or supplementary intravenous fluids, collectively referred to as parenteral support, in patients with intestinal failure due to MVID and short bowel syndrome by up to 27% and 12.5% respectively." The objective of the prospective, randomized, open-label field study in dogs undergoing chemotherapy treatment across the U.S. is to collect real-world data to demonstrate real-world evidence of the clinical effectiveness for Canalevia-CA1 for the treatment of CID in dogs to support potential full FDA approval of the drug for this indication. Dogs enrolled in this study will be randomly assigned to receive a prescription of Canalevia-CA1 as a treatment for CID or be randomly selected to the control group. As announced, Jaguar established a new Investigational New Animal Drug (INAD) file with the FDA's Center for Veterinary Medicine for crofelemer to treat general, non-infectious diarrhea in dogs. Diarrhea is one of the most common reasons for veterinary office visits for dogs and is the second most common reason for visits to the veterinary emergency room, yet there are currently no FDA-approved drug to treat canine general, non-infectious diarrhea. According to the American Veterinary Medical Association , there were an estimated 89.7 million dogs in the United States in 2024, with nearly half (45.5%) of U.S. households owning a dog in 2024. Devastating diarrhea-related dehydration can occur rapidly for the animal, and the lack of control in urban settings where owners don't have easy access to outdoor facilities is a significant problem for families with dogs. Canalevia-CA1, a canine-specific formulation of crofelemer, Jaguar's novel, oral plant-based drug sustainably harvested from the Croton lechleri tree, is available from multiple leading veterinary distributors in the U.S. , including Chewy. About Conditional Approval and Full Approval Canalevia-CA1 initially received conditional approval in December 2021 from the FDA for the treatment of CID in dogs. FDA's conditional approval allows a drug company to legally promote, advertise and sell the animal drug for the labeled uses before proving it meets the "substantial evidence" standard of effectiveness for full approval. The conditional approval is valid for one year. The drug company can ask the FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. To receive a renewal from the FDA, the company must show active progress toward proving "substantial evidence of effectiveness" for full approval. After collecting the remaining effectiveness data, the company then applies to the FDA for full approval. The FDA reviews the application and, if appropriate, fully approves the drug. About Chemotherapy-induced Diarrhea (CID) in Dogs According to the American Veterinary Medical Association , approximately 1 in 4 dogs will, at some stage in their life, develop cancer, and almost 50% of dogs over age 10 will develop cancer.1 According to the National Cancer Institute , which is part of the National Institutes of Health , roughly 6 million new cancer diagnoses are made in dogs each year in the U.S. Due to the increasing number of chemotherapeutic agents being adopted by veterinary oncologists and primary care veterinarians, chemotherapy is fast becoming the most widely used cancer treatment in veterinary medicine. Studies have found the incidence of CID to be one of the three most prevalent side effects in dogs undergoing cancer treatment,2 and managing side-effects such as diarrhea can be important to maintain successful cancer treatment. More than half of the U.S. veterinarians who responded to a Jaguar-sponsored survey reported that CID interferes with their patients' chemotherapy treatment plans, indicating an unmet need for an effective product for the treatment of CID. Canalevia-CA1 is a tablet that can be given orally twice a day and can be used for home treatment of CID in dogs. About Canalevia®-CA1 Canalevia-CA1 (crofelemer delayed-release tablets) is the first and only oral plant-based prescription product that is FDA conditionally approved to treat chemotherapy-induced diarrhea (CID) in dogs. Canalevia-CA1 is a canine-specific formulation of crofelemer, an active pharmaceutical ingredient isolated and purified from the Croton lechleri tree. Canalevia-CA1 is currently conditionally approved by the FDA under application number 141-552. Conditional approval allows for commercialization of the product while Jaguar continues to collect the substantial evidence of effectiveness required for full approval. Jaguar has also received Minor Use in a Major Species (MUMS) designation from the FDA for Canalevia-CA1 to treat CID in dogs. FDA has established a "small number" threshold for minor use in each of the seven major species covered by the MUMS act. The small number threshold is currently 80,000 for dogs, representing the largest number of dogs that can be affected by a disease or condition over the course of a year and still have the use qualify as a minor use. About Crofelemer Crofelemer is the only oral FDA-approved prescription drug under botanical guidance. It is plant-based, extracted and purified from the red bark sap of the Croton lechleri tree in the Amazon Rainforest. Napo Pharmaceuticals , a Jaguar family company, has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities. Important Safety Information About Canalevia®-CA1 For oral use in dogs only. Not for use in humans. Keep Canalevia-CA1 (crofelemer delayed-release tablets) in a secure location out of reach of children and other animals. Consult a physician in case of accidental ingestion by humans. Do not use in dogs that have a known hypersensitivity to crofelemer. Prior to using Canalevia-CA1, rule out infectious etiologies of diarrhea. Canalevia-CA1 is a conditionally approved drug indicated for the treatment of chemotherapy-induced diarrhea in dogs. The most common adverse reactions included decreased appetite, decreased activity, dehydration, abdominal pain, and vomiting. Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Use only as directed. It is a violation of Federal law to use this product other than as directed in the labeling. Conditionally approved by FDA pending a full demonstration of effectiveness under application number 141-552. About the Jaguar Health Family of Companies Jaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals (Napo) focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar's Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications. For more information about: Jaguar Health , visit https://jaguar.health Napo Pharmaceuticals , visit www.napopharma.com Napo Therapeutics, visit napotherapeutics.com Magdalena Biosciences, visit magdalenabiosciences.com Visit the Make Cancer Less Shitty patient advocacy program on Bluesky, X, Facebook & Instagram Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding Jaguar's expectation that it will identify a partner to fund and execute development and commercialization of crofelemer for the treatment of general, non-infectious diarrhea in dogs in the U.S and/or globally, Jaguar's expectation that the U.S. population of metastatic breast cancer patients meets the requirements for orphan drug status, Jaguar's expectation that it will promptly establish an expanded access program for crofelemer for cancer therapy-related diarrhea in breast cancer patients, and Jaguar's expectation that the field study of Canalevia-CA1 for the treatment of CID in dogs will support potential full FDA approval of the drug for this indication. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 1 "Cancer in Pets." American Veterinary Medical Association , 2021, https://www.avma.org/resources/pet-owners/petcare/cancer-pets 2 Mason SL, Grant IA , Elliott J, Cripps P, Blackwood L. Gastrointestinal toxicity after vincristine or cyclophosphamide administered with or without maropitant in dogs: a prospective randomised controlled study. J Small Anim Pract. 2014;55:391-398 Contact: hello@jaguar.health Jaguar-JAGX SOURCE: Jaguar Health, Inc.

Drug ApprovalClinical ResultOrphan Drug

09 Jun 2025

·jaguarhealth.gcs-web.com

Jaguar Health Provides Update on Meeting with FDA Discussing Statistically Significant Results of Responder Analysis of Breast Cancer Patients in Phase 3 OnTarget Trial and Potential Approval Pathway for Crofelemer

Productive and collaborative discussion on proposed pathway by the company to bring crofelemer to approval for cancer therapy-related diarrhea (CTD) in patients with metastatic breast cancer receiving selected targeted therapies The currently estimated US metastatic breast cancer population would qualify as an orphan population, which aligns with company's core focus on orphan diseases Company plans to promptly pursue authorization to initiate expanded access program for patients with breast cancer who may not be eligible for a potential pivotal treatment trial with crofelemer in patients with metastatic breast cancer SAN FRANCISCO, CA / ACCESS Newswire / June 9, 2025 / Jaguar Health, Inc. (NASDAQ:JAGX) (Jaguar) family company Napo Pharmaceuticals (Napo) today provided a recap on the company's assessment of the in-person Type C Meeting on May 28, 2025 with the Division of Gastroenterology of the U.S. Food and Drug Administration (FDA) to discuss the statistically significant responder analysis results for adult patients with breast cancer in Napo's recently conducted Phase 3 OnTarget trial. "We were very happy to take part in the face-to-face Type C Meeting, the catalyst for which was the positive data in the subpopulation of breast cancer patients from our OnTarget trial," said Lisa Conte , Jaguar's founder, president, and CEO. "Napo proposed two simultaneous potential pathways during the meeting for making crofelemer available to metastatic breast cancer patients with the significant unmet medical need of CTD: conducting a pivotal treatment trial to facilitate approval of crofelemer for CTD in this focused patient population; and the prompt pursuit of authorization 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. We are pleased with the constructive and productive discussion that took place with the FDA during the meeting. Last week the FDA formally acknowledged both of these key discussion points in correspondence to Napo. We plan to submit a protocol to the FDA for a pivotal treatment trial for a smaller number of metastatic breast cancer patients using crofelemer." Patient advocates participated in the Type C Meeting to share their raw and personal experience with CTD, including a metastatic breast cancer patient with uncontrollable diarrhea who received a prescription for crofelemer. "The design of the protocol for OnTarget was based on a survey of cancer patients. Today there are close to 100 approved targeted cancer agents. Thanks to these amazing drugs, metastatic cancer patients are living longer, frequently rendering cancer, and CTD, chronic ailments with which to live. To deepen our understanding of the current population of metastatic cancer breast with CTD, and ensure the clinical meaningfulness of the design of the anticipated pivotal treatment trial, we plan to conduct a new survey of this cancer patient population," Conte said. The currently estimated US metastatic breast cancer population potentially qualifies as an orphan population, in alignment with the company's core focus on orphan diseases. The company 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. "Embracing a sharp strategic focus on orphan indications seems to fit with the new administration's efforts and philosophy," said Conte. "Dr. Marty Makary , the new Commissioner of the FDA, commented in April 2025 that the agency will open a new regulatory pathway based on what he called a ‘plausible mechanism,' focusing mainly on rare or incurable diseases." As expressed during the Type C Meeting, the data from the first-of-its-kind prophylactic OnTarget study is invaluable, providing new insights into the natural history of the important and debilitating side effect of CTD. Diarrhea is a common side effect of targeted cancer therapies and can lead to dose changes, treatment delays, and often cessation of lifesaving cancer therapy. The benefit to risk ratio of crofelemer is well-documented, as the active agent has been commercialized for the approved indication of HIV-related diarrhea since 2012, with no crofelemer-related reported serious adverse events. In both the US and European Union , crofelemer has been granted orphan drug designation for the orphan diseases of short bowel syndrome with intestinal failure and microvillus inclusion disease. Crofelemer has been granted orphan drug designation for treatment of diarrhea in cholera in the US, where cholera is an orphan disease. Orphan drug designation in the US qualifies the sponsor of a drug for various development incentives, including tax credits for qualified clinical testing and relief of filing fees. Additionally, orphan drug designation in the US provides a seven-year period of marketing exclusivity to the first sponsor who obtains marketing approval for the designated orphan drug. While the multicenter, double-blind, placebo-controlled OnTarget pivotal trial did not meet its primary endpoint, the subgroup of adult breast cancer patients achieved statistically significant results in the responder analysis. In the responder analysis of patients with breast cancer on targeted therapies, crofelemer CTD prophylaxis resulted in a greater proportion of monthly responders of diarrhea improvement compared to placebo. Patients with breast cancer accounted for 183 of the 287 participants in this unprecedented prophylactic clinical trial of crofelemer for diarrhea in adults with 10 solid tumor types receiving targeted therapy with or without standard chemotherapy. The OnTarget 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 have been accepted for presentation as an oral rapid e-poster at the Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting in June 2025 in Seattle, Washington . About Crofelemer Crofelemer is a novel, oral plant-based prescription medicine purified from the red bark sap, also referred to as "dragon's blood," of the Croton lechleri tree in the Amazon Rainforest. Napo has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for indigenous communities. About the Jaguar Health Family of Companies Jaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals (Napo) focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Napo's crofelemer is FDA-approved under the brand name Mytesi® for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar's Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications. For more information about: Jaguar Health , visit https://jaguar.health Napo Pharmaceuticals , visit www.napopharma.com Napo Therapeutics, visit napotherapeutics.com Magdalena Biosciences, visit magdalenabiosciences.com Visit the Make Cancer Less Shitty patient advocacy program on Bluesky, X, Facebook & Instagram Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding Jaguar's expectation that the currently estimated US metastatic breast cancer population qualifies as an orphan population, Jaguar's expectation that the company will submit a protocol to the FDA for a pivotal treatment trial for a smaller number of metastatic breast cancer patients using crofelemer, Jaguar's expectation that it will promptly pursue authorization to initiate an expanded access program for patients with breast cancer who may not be eligible for a potential pivotal treatment trial with crofelemer in patients with metastatic breast cancer patients, and that the expanded access program would potentially include breast cancer patients in the adjuvant and neoadjuvant settings, Jaguar's expectation that Napo will conduct a clinical trial of crofelemer for treatment of CTD in patients with metastatic breast cancer, Jaguar's 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, and Jaguar's expectation that additional significant results in adult breast cancer patients from the OnTarget study will be presented at the 2025 MASCC Annual Meeting. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to several risks, uncertainties, and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: hello@jaguar.health Jaguar-JAGX SOURCE: Jaguar Health, Inc.

Clinical ResultOrphan DrugPhase 3Fast TrackDrug Approval

20 May 2025

·jaguarhealth.gcs-web.com

First Patient Randomized in Jaguar Health’s Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Crofelemer in Pediatric Patients with Microvillus Inclusion Disease (MVID)

As announced, initial proof-of-concept (POC) results from distinct ongoing investigator-initiated trial (IIT) in Abu Dhabi show crofelemer reduced total parenteral support in a pediatric MVID patient with intestinal failure by up to 27%; per the IIT protocol, patient was taken off crofelemer after 12 weeks of treatment for a period of 30 days, but was restarted on daily crofelemer treatment after just 8 days, as patient's symptoms were worsening Additional POC IIT results expected throughout 2025 for MVID; results from company's MVID Phase 2 study expected with completion of treatment in H2 2026 Ground-breaking results in single-digit number of MVID patients could potentially lead to expedited approval in the EU through PRIME and to Breakthrough Therapy designation in the US SAN FRANCISCO, CA / ACCESS Newswire / May 20, 2025 / Jaguar Health, Inc. (NASDAQ:JAGX) (Jaguar) family companies Napo Pharmaceuticals, Inc. (Napo) and Napo Therapeutics S.p.A. today announced that the first patient has been randomized in Napo's randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the safety and efficacy of the novel crofelemer oral powder for solution formulation in pediatric patients with intestinal failure due to the ultrarare disease MVID. Patients with MVID suffer from devastating diarrhea and dehydration caused by this debilitating, lifelong condition. These pediatric patients often require lifelong and life-sustaining total parenteral nutrition (TPN) with additional supplemental intravenous (IV) fluids, termed total parenteral support, which is the standard of care for MVID, for up to 7 days a week greater than 50% of the time each day to provide adequate nutrient and electrolyte support. While crucial for MVID patients, TPN carries a significant risk of morbidity and mortality due to infections, metabolic complications, liver and/or kidney disease, and a risk of neurodevelopmental delay. There are currently no approved drug treatments for MVID. As previously announced, and as presented last month at the 11th Annual ELITE PED-GI Congress in Abu Dhabi in the United Arab Emirates , the initial proof-of-concept results from the ongoing and independent proof-of-concept investigator-initiated trial (IIT) at Sheikh Khalifa Medical City (SKMC) showed that crofelemer reduced the required TPN and/or supplementary intravenous fluids - collectively referred to as parenteral support - in the first participating MVID patient by up to 27% at the end of 12-weeks of crofelemer treatment. In addition, this data showed that crofelemer reduced stool volume output and/or frequency of watery stools, and increased urine output - an indicator of improved nutrient oral absorption. Per the protocol for the IIT at SKMC, the pediatric MVID patient was taken off crofelemer after 12 weeks of treatment for a period of 30 days. After just 8 days, the patient's parents requested reinitiation of crofelemer dosing, as the patient's symptoms were worsening - evidenced by increased stool output and decreased urine output. Hence, the patient was restarted on daily treatment with crofelemer. "We're very happy that the first patient has been randomized in Napo's randomized, double-blind placebo-controlled Phase 2 clinical trial of crofelemer in pediatric MVID patients," said Lisa Conte , Jaguar's founder, president, and CEO. "This is another important milestone in development efforts for crofelemer for the treatment and management of intestinal failure related to this devastating ultrarare pediatric disease. For this study, randomization represents the key milestone of assigning a participating patient to either the crofelemer or placebo treatment group in a double-blind, placebo-controlled within-patient crossover study." "Additional proof-of-concept results for MVID from the ongoing IIT of crofelemer at SKMC in pediatric patients with intestinal failure due to MVID and other disorders are expected throughout 2025," Conte said. "The results of Napo's randomized double-blind, placebo-controlled Phase 2 study of crofelemer in pediatric MVID patients are expected to be available in the second half of 2026. Because the IIT of crofelemer for MVID is an unblinded, open-label study, results from this IIT are expected to be available sooner." Based on the initial proof-of-concept findings presented last month at the 11th Annual ELITE PED-GI Congress , crofelemer's novel antisecretory mechanism of action appears to have the potential to provide a novel therapeutic option to modify the disease progression associated with intestinal failure due to MVID in pediatric patients, as evidenced by the reductions in total parenteral support and potential to improve the quality of life of MVID patients. "Based on preliminary communications with European Medicines Agency (EMA) regulatory members that focus on PRIME (Priority Medicines), a program that provides enhanced interactions and early dialogue for development of novel medicines targeting unmet medical needs, we are excited by the initial findings from the IIT being conducted at SKMC," said Conte. "We are not aware of any other intervention that has shown the ability to reduce the required administration of life-sustaining parenteral support including TPN, thus potentially improving nutrient absorption in patients with MVID. Given the ultrarare nature of MVID, even a small number of MVID patients showing benefit with crofelemer may allow Napo to explore pathways for expedited regulatory approval in the European Union . Crofelemer may qualify for participation in PRIME in the European Union for MVID and potentially in the U.S. Food and Drug Administration's (FDA) Breakthrough Therapy program for this ultrarare pediatric indication. Additionally, in accordance with the guidelines of specific EU countries, published data from clinical investigations in MVID could support reimbursed early patient access to crofelemer for this debilitating condition." About Crofelemer Crofelemer is a novel, oral plant-based prescription medicine purified from the red bark sap, also referred to as "dragon's blood," of the Croton lechleri tree in the Amazon Rainforest. Napo has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for indigenous communities. About the Jaguar Health Family of Companies Jaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals (Napo) focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Napo's crofelemer is FDA-approved under the brand name Mytesi® for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar's Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications. For more information about: Jaguar Health , visit https://jaguar.health Napo Pharmaceuticals , visit www.napopharma.comNapo Therapeutics, visit napotherapeutics.comMagdalena Biosciences, visit magdalenabiosciences.com Visit the Make Cancer Less Shitty patient advocacy program on Bluesky, X, Facebook & Instagram Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding Jaguar's expectation that additional POC results for MVID from the IIT in pediatric patients with intestinal failure due to MVID and other disorders may be available throughout 2025, Jaguar's expectation that results from the company's MVID Phase 2 study will be available with completion of treatment in H2 2026, Jaguar's expectation that crofelemer's novel antisecretory mechanism of action may have the potential to provide a novel therapeutic option to modify the disease progression associated with intestinal failure due to MVID in pediatric patients and the potential to improve the quality of life of MVID patients, Jaguar's expectation that, given the ultrarare nature of MVID, even a small number of MVID patients showing benefit with crofelemer may allow Napo to explore pathways for expedited regulatory approval in the Europe Union , Jaguar's expectation that crofelemer may qualify for participation in PRIME in the European Union for MVID and potentially in the FDA's Breakthrough Therapyprogram, and Jaguar's expectation that, in accordance with the guidelines of specific EU countries, published data from clinical investigations in MVID could support reimbursed early patient access to crofelemer for this debilitating condition. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to several risks, uncertainties, and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: hello@jaguar.healthJaguar-JAGX SOURCE: Jaguar Health, Inc.

Phase 2Clinical ResultDrug ApprovalBreakthrough Therapy

100 Deals associated with Crofelemer

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KEGG	Wiki	ATC	Drug Bank
D03605	Crofelemer	A07XA06	DB04941

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diarrhea	United States	Napo Pharmaceuticals, Inc.	31 Dec 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Enteropathy	Phase 3	United States	Bausch Health Americas, Inc.	01 Oct 2007
HIV Enteropathy	Phase 3	Puerto Rico	Bausch Health Americas, Inc.	01 Oct 2007
Acquired Immunodeficiency Syndrome	Phase 3	United States	Shaman Pharmaceuticals, Inc.	31 Aug 2001
Acquired Immunodeficiency Syndrome	Phase 3	Puerto Rico	Shaman Pharmaceuticals, Inc.	31 Aug 2001
Short Bowel Syndrome	Phase 2	Germany	Napo Therapeutics SpA	29 May 2025
Short Bowel Syndrome	Phase 2	Italy	Napo Therapeutics SpA	29 May 2025
Microvillus Inclusion Disease	Phase 2	United States	Napo Pharmaceuticals, Inc.	01 May 2025
Microvillus Inclusion Disease	Phase 2	Italy	Napo Pharmaceuticals, Inc.	01 May 2025
Microvillus Inclusion Disease	Phase 2	United Arab Emirates	Napo Pharmaceuticals, Inc.	01 May 2025
Irritable bowel syndrome with diarrhea	Phase 2	United States	Bausch Health Americas, Inc.	01 Dec 2004

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Company_Website Manual	Not Applicable	Microvillus Inclusion Disease	1	Crofelemer	zryfsvwequ(zsqrjdgvkx) = xifotysmll jocxgkeqwc (aiajqyzmdq )	Positive	20 May 2025
NCT04538625 (OnTARGET, Company_Website) Manual	Phase 3	Diarrhea	287	crofelemer	ntqviubqom(vznjutbkzi) = 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 oimgkpnhls (ayjmzfkgrv ) Met	Positive	27 Mar 2025
				Placebo
NCT04538625 (OnTarget, Company_Website) Manual	Phase 3	Diarrhea	287	Crofelemer	ftbthlwiva(lfdaqooaha) = mlydcxsbge gwdnfpjnfv (wxbfuxkixh )	Positive	12 Dec 2024
				Placebo	ftbthlwiva(lfdaqooaha) = hjihnomepu gwdnfpjnfv (wxbfuxkixh )
NCT04486326 (Company_Website) Manual	Phase 4	Diarrhea	-	Crofelemer	ishbbaurol(kyyiexrkxr) = statistically meaningful reduction toyoavwxpf (omnohayelk )	Positive	28 May 2024
				Placebo
NCT02910219 (Pubmed) Manual	Phase 2	HER2 Positive Breast Cancer HER2 Positive	51	crofelemer	tkybsfsotb(sxxfcxjqii) = keikfpwnsl xdumvodcpo (llkdlwrggu ) View more	Negative	25 Oct 2022
				no scheduled prophylactic medication	tkybsfsotb(sxxfcxjqii) = yxhbbrvfmh xdumvodcpo (llkdlwrggu ) View more
NCT02910219 (HALT-D, CTgov)	Phase 2	Diarrhea	53	Crofelemer (Crofelemer)	egzgdzehjk = vnhxryuiqc aqwonrveto (zgrtuzckjj, lbgmyjdymd - eueyggqxjh) View more	-	24 Oct 2022
				THP (Control)	egzgdzehjk = ohfpatbyqf aqwonrveto (zgrtuzckjj, ziddxgsitl - kxvzssnobj) View more
NCT02910219 (Halt-d, SABCS2022)	Phase 2	Breast Cancer Neoadjuvant \| Adjuvant HER2+	53	Crofelemer	iujnlehhwe(paoksltytj) = bfgjqitrre tsuesuykxb (tztzoywnze ) View more	Positive	15 Feb 2022
				Control	iujnlehhwe(paoksltytj) = ehfoztkude tsuesuykxb (tztzoywnze ) View more
NCT02910219 (HALT-D, Company_Website) Manual	Phase 2	Diarrhea	51	Crofelemer	tftinpeevy(ypssfyjxxt) = not statistically different for the two groups jzhiyrtzgy (dxupvagapz )	Negative	10 Dec 2021
				standard of care
NCT00547898 (ADVENT, CTgov)	Phase 3	HIV Enteropathy	374	Placebo (Placebo)	tfpwwkymoe(zcmjwoprkd) = gbmnwxkrhh ntvlyegpyr (bwrpovxayv, qvfegxsgcf - zrcwcjkufd) View more	-	03 Sep 2020
				Crofelemer 125 mg (Crofelemer 125 mg)	tfpwwkymoe(zcmjwoprkd) = sfcutetgcm ntvlyegpyr (bwrpovxayv, wsvofgdytd - urzmfihbop) View more
NCT01374490 (CTgov)	Phase 3	Diarrhea \| HIV Enteropathy	250	Crofelemer	yeegcdcyrc = mtohfyqqij feypnanmci (ggbwdjefjg, pdcrhsthmf - aichgsjdwk) View more	-	17 Aug 2020

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