Mytesi (crofelemer) / Jaguar Health, Knight Therap - LARVOL DELTA

Jaguar Health Secures New Patent for Crofelemer in Short Bowel Syndrome, Strengthening Global IP Position Ahead of Additional Clinical Milestones (ACCESS Newswire) - "This new IP supports crofelemer's global exclusivity in rare pediatric intestinal failure coincident with published clinical data showing reductions in parenteral support requirements with crofelemer - supporting Jaguar's strategy to secure non-dilutive partnership funding."

Patent • Short Bowel Syndrome

Jaguar Health Completes Meeting with FDA for Advice on Development Pathways to Advance Ongoing Crofelemer Trial for Potential Approval for Treatment of Pediatric Indication Microvillus Inclusion Disease (MVID) (ACCESS Newswire) - "As stated above, the results of the ongoing investigator-initiated proof-of-concept trial in the UAE in a pediatric MVID patient demonstrate continued improvement of reduction of PS by 37% with a total parenteral nutrition (TPN) reduction of 30%. This improvement has been observed since reinitiation of crofelemer oral dosing following the protocol-mandated drug cessation at 12 weeks. The weekly reductions in PS and TPN of 37% and 30% are higher than the previously reported PS reduction of 27% at 12 weeks in this patient....An abstract describing partial results of the IIT in the UAE has been accepted for presentation at the upcoming North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Annual Meeting taking place November 5-8, 2025 in Chicago."

FDA event • P2 data • Genetic Disorders • Rare Diseases

Jaguar Health Submits Orphan Drug Designation Application to FDA for Crofelemer for Cancer Therapy-Related Diarrhea (CTD) in Patients with Breast Cancer with Metastasis Identified by FDA as a Distinct Condition (ACCESS Newswire)

Orphan drug • Gastrointestinal Disorder

ONTARGET: CROFELEMER OR PLACEBO FOR THE PROPHYLAXIS OF DIARRHEA IN ADULTS WITH SOLID TUMORS INITIATING TARGETED THERAPY ± CHEMOTHERAPY (TT/C) (MASCC-ISOO 2025) - P3 | "Conclusions A greater proportion of PBCs on crofelemer versus placebo achieved an earlier onset of DR status and sustained prophylaxis of CTD via MR analysis while on TT/C for 3 months. The sustained efficacy and favorable safety profile of crofelemer supports its use for CTD prophylaxis in PBCs receiving TT/C."

Clinical • Breast Cancer • Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Oncology • Respiratory Diseases • Solid Tumor • CFTR

Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID) (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Napo Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Pediatrics • Rare Diseases

CRO-SBS-IF: Safety and Efficacy of Crofelemer in Adult Patients With Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC) (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Napo Therapeutics, S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Short Bowel Syndrome

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 (Jaguar Press Release) - "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 plan to submit a protocol to the FDA for a pivotal treatment trial for a smaller number of metastatic breast cancer patients using crofelemer....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."

FDA event • New trial • P3 data • Breast Cancer

Metabolomic, Microbiome and Transcriptomic Study of Crofelemer or Loperamide in Rat Model of Afatinib-induced Intestine Epithelial Damage and Diarrhea (ATS 2025) - "Loperamide and crofelemer attenuate afatinib-induced diarrhea and intestinal damage in rats, possibly through regulating microbiota-metabolic axis. The current research shows the underlying protective mechanisms of antidiarrheal agents in TKI-induced diarrhea."

Late-breaking abstract • Preclinical • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR • IL17A • IL1B • IL6 • TNFA

Proof-of-Concept Data for Rare Disease Indications MVID and SBS-IF for Jaguar Health's Crofelemer to be Presented at April 2025 ELITE PED-GI Congress (ACCESSWIRE) - P2 | N=12 | NCT06721871 | Sponsor: Napo Pharmaceuticals, Inc. | "Jaguar Health...announced that preliminary results from the ongoing pediatric investigator-initiated trial (IIT) of a novel liquid formulation of crofelemer, Jaguar's novel plant-based anti-secretory prescription drug, for various congenital diarrheal disorders (CDD), including MVID and SBS with intestinal failure (SBS-IF), will be presented by Dr. Mohamad Miqdady at the April 24-26, 2025 Annual ELITE PED-GI Congress in Abu Dhabi in the United Arab Emirates...This ongoing proof-of-concept study is evaluating crofelemer's potential to be safely administered to patients with MVID, SBS-IF, and other CDDs in escalating doses, improve stool formation, improve the absorption of nutrients, and lower TPN needs - which have never been achieved in an MVID patient."

Clinical data • Gastrointestinal Disorder • Short Bowel Syndrome

CRO-SBS-IF: Safety and Efficacy of Crofelemer in Adult Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC) (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Napo Therapeutics, S.p.A.

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Short Bowel Syndrome

Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Lindsey Russell, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder • Short Bowel Syndrome

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea in Non-HIV Patients (clinicaltrials.gov) - P4 | N=93 | Completed | Sponsor: The University of Texas Health Science Center, Houston | Recruiting ➔ Completed | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial completion • Trial primary completion date • Infectious Disease

Natural history including the incidence, severity and management of diarrhea in patients with breast cancer receiving abemaciclib and pertuzumab-based therapies with or without standard chemotherapy: Data from placebo arm of the OnTarget study (SABCS 2024) - P3 | "Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and antidiarrheal or antibiotic use ≤7 days...Patients were randomized 1:1 to placebo (n=142) or crofelemer (n=145) to prevent diarrhea...In contrast, those receiving pertuzumab/trastuzumab/docetaxel and carboplatin [n=17] had maximum median grade diarrhea during cycle 1 with 7.1 LWS/week (IQR: 4.6-12.3), and 75% of these patients reported rescue loperamide use... This PRO-based prophylactic study on the incidence of diarrhea in patients with breast cancer receiving abemaciclib or pertuzumab-based therapies with standard chemotherapy over a 12-week period showed that most patients with breast cancer required dose modifications due to diarrhea and/or used rescue medications to remain on their cancer therapy. The use of real-time PRO data on CTD in adult patients with breast cancer shows that diarrhea remains a neglected and under-reported comorbidity of cancer..."

Clinical • Breast Cancer • Oncology • Solid Tumor

OnTarget crofelemer diarrhea prophylaxis trial: responder analysis of patients with breast cancer receiving targeted therapy with or without chemotherapy (SABCS 2024) - P3 | "Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and any antidiarrheal or antibiotic use ≤7 days...A total of 184 (64.1%) patients with breast cancer participated; median age 57 yrs [IQR: 48-65 yrs], 16.5% non-White); 96 (54.6%) received abemaciclib, 67 (38.1%) pertuzumab/trastuzumab, and 13 (7.4%) kinase inhibitors... In this 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, with better-sustained response in those with preserved functional status (ECOG 0-1)."

Clinical • Breast Cancer • Oncology • Solid Tumor • CFTR

Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID) (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Napo Pharmaceuticals, Inc.

New P2 trial • Pediatrics • Rare Diseases

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Neurolief Ltd. | N=57 ➔ 0 | Trial completion date: Jun 2025 ➔ Nov 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jun 2025 ➔ Nov 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • CNS Disorders • Migraine • Pain

Crofelemer Improves Symptoms of Chronic Idiopathic Diarrhea (ACG 2024) - "Outcomes were available for 19 patients with chronic idiopathic diarrhea who completed a 28-day course of crofelemer (74% female; mean age 57.2 years). Two patients (10.5%) described worsening diarrhea, 6 (31.6%) described a neutral effect, and 11 (57.9%) improved with crofelemer (Figure 1). Using a binary outcome, 58.8% (11/19) improved with crofelemer while 42.1% (8/19) did not improve."

Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases

Pilot Study of Crofelemer for Functional Diarrhea (ACG 2024) - "17 FDr patients completed the 4 week double blind period (crofelemer n=9, placebo=8). Average BSFS decreased from 5.88 +/- 0.35 (mean +/- SD) at baseline to 5.28 +/- 0.66 in the crofelemer group. Average BSFS decreased from 6.09 +/- 0.60 to 5.85 +/- 0.74 in the placebo group."

Clinical • Constipation • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Pain

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=57 | Not yet recruiting | Sponsor: Neurolief Ltd. | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

OnTARGET: Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy (clinicaltrials.gov) - P3 | N=287 | Completed | Sponsor: Napo Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Oct 2023 | Trial primary completion date: Apr 2024 ➔ Aug 2023

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Lindsey Russell, MD

New P1 trial • Gastrointestinal Disorder • Short Bowel Syndrome

OnTARGET: Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy (clinicaltrials.gov) - P3 | N=256 | Active, not recruiting | Sponsor: Napo Pharmaceuticals, Inc. | Trial primary completion date: Nov 2023 ➔ Mar 2024

Trial primary completion date • Oncology • Solid Tumor

Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for Preventive Treatment of Migraine (clinicaltrials.gov) - P=N/A | N=57 | Not yet recruiting | Sponsor: Neurolief Ltd. | Trial completion date: Aug 2024 ➔ Dec 2024 | Initiation date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Aug 2024 ➔ Dec 2024

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Migraine • Pain

Effects of orally administered crofelemer on the incidence and severity of neratinib-induced diarrhea in female dogs. (PubMed, PLoS One) - "The average number of weekly loose/watery stools were not different between the crofelemer BID and QID treatment groups (p = 0.84). This study showed that crofelemer prophylaxis reduced the incidence/severity of neratinib-associated diarrhea in female beagle dogs without the need for any loperamide administration."

Journal • Breast Cancer • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • EGFR