Jaguar Health's subsidiary Napo Pharmaceuticals has secured a meeting with the U.S. Food and Drug Administration (FDA) to discuss promising results from its Phase 3 OnTarget study, which showed significant benefits of crofelemer in preventing diarrhea specifically in breast cancer patients undergoing targeted therapy.
The FDA has granted Napo a Type C Meeting scheduled for the second quarter of 2025. The discussion will focus on the responder analysis in the prespecified subgroup of breast cancer patients, who represented a substantial portion of the study population—183 out of 287 total participants.
"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," said Lisa Conte, Jaguar's president and CEO. "We are very happy to have been granted a meeting with the FDA to review the positive OnTarget results in breast cancer patients and our goal is to discuss the most efficient pathways to make crofelemer available to this patient population."
Study Background and Significance
The OnTarget trial was a multicenter, double-blind, placebo-controlled pivotal clinical study investigating crofelemer for the prophylaxis of diarrhea in adults with solid tumors receiving targeted therapy with or without standard chemotherapy. While the initial top-line results did not meet the primary endpoint across all tumor types, subsequent analysis revealed significant benefits specifically in the breast cancer subgroup.
Crofelemer, marketed under the brand name Mytesi®, is already FDA-approved for symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. The potential expansion to cancer therapy-related diarrhea (CTD) in breast cancer patients could address a significant unmet need.
The American Cancer Society expects 316,950 new cases of breast cancer to be diagnosed in women in the US in 2025, and an estimated 4 million US women had a history of invasive breast cancer in 2022, highlighting the substantial patient population that could benefit from this treatment.
Upcoming Scientific Presentations
Napo has submitted a late-breaker abstract to the Multinational Association of Supportive Care in Cancer (MASCC) detailing additional significant results in adult breast cancer patients from the OnTarget study. The abstract has been accepted for presentation as an oral rapid e-poster at MASCC's Annual Meeting in Seattle, Washington, scheduled for June 26-28, 2025.
The abstract, titled "OnTarget: Crofelemer or Placebo for the Prophylaxis of Diarrhea in Adults with Solid Tumors Initiating Targeted Therapy +/- Chemotherapy," includes contributions from Pravin Chaturvedi, PhD, Jaguar's Chief Scientific Officer and Chair of Napo's Scientific Advisory Board, along with leading oncologists and cancer patient advocates.
Additionally, a second late-breaker abstract related to the results of a recent Napo-sponsored screening survey of cancer patients about oral mucositis and a follow-up focus group has also been accepted for presentation at the MASCC Annual Meeting. This abstract is titled "Beyond the Pain: Patient Insights on Oral Mucositis in Cancer Treatment."
Patient Perspective and Clinical Significance
Dr. Kelly Shanahan, a former clinician and current metastatic breast cancer patient who serves on Napo's Scientific Advisory Board, emphasized the importance of this development: "As a cancer patient, having options to manage the side effects of life-saving drugs is very important. I believe the published results of crofelemer for the prophylaxis of CTD are very exciting and compelling."
The responder analysis of breast cancer patients on targeted therapies showed that crofelemer prophylaxis resulted in a greater proportion of monthly responders with diarrhea improvement compared to placebo. Overall, crofelemer demonstrated significantly greater effectiveness than placebo in providing sustained response in breast cancer patients.
Potential Impact on Cancer Treatment
Cancer therapy-related diarrhea is not merely a quality-of-life issue—it can directly impact treatment outcomes. When patients experience severe diarrhea, oncologists often must modify treatment regimens by reducing dosages, delaying treatment cycles, or in some cases, discontinuing effective therapies altogether. These modifications can potentially compromise the efficacy of cancer treatment.
By preventing or reducing the severity of diarrhea, crofelemer could enable more patients to maintain their prescribed treatment regimens at full dosage and on schedule, potentially improving overall treatment outcomes.
Members of Napo's Scientific Advisory Board are expected to join Jaguar representatives at the FDA meeting, bringing both scientific expertise and patient perspective to the discussion about potential regulatory pathways for this indication.
About Crofelemer and Jaguar Health
Crofelemer is a novel, oral plant-based prescription medicine derived sustainably from the Croton lechleri tree in the Amazon rainforest. It works locally in the gut by normalizing ion and fluid transport across the intestinal epithelium, addressing the underlying mechanisms of watery diarrhea.
Jaguar Health, Inc. is a commercial-stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants for people and animals with gastrointestinal distress, specifically associated with overactive bowel symptoms. The company operates through several subsidiaries, including Napo Pharmaceuticals, which focuses on human prescription pharmaceuticals for essential supportive care.
If approved for cancer therapy-related diarrhea in breast cancer patients, crofelemer would represent an important addition to the supportive care arsenal for oncologists and their patients, potentially improving both quality of life and treatment outcomes for a substantial patient population.
