Mytesi Seeks FDA Orphan Drug Designation in Breast Cancer Diarrhea

Napo Pharmaceuticals has submitted an orphan drug designation application to the U.S. Food and Drug Administration (FDA) for novel prescription drug Mytesi (crofelemer) for the treatment of diarrhea among adult patients with breast cancer that has metastasized to the brain who are receiving targeted therapy with or without standard chemotherapy.

The development was announced in a news release issued by Jaguar Health, which explained that Napo Pharmaceuticals is a Jaguar family company.

"The FDA has identified the condition of breast cancer that has metastasized to the brain as an orphan indication. We have submitted this [orphan drug designation] application for [Mytesi] to treat diarrhea in these patients," said Lisa Conte, Jaguar's founder, president, and CEO in the news release. "Diarrhea is a common side effect of numerous targeted cancer therapies that can lead to dose changes, treatment delays or cessation of treatment altogether, all of which impact patient outcomes. Given [Mytesi] novel and physiological mechanism of action, we would plan to seek breakthrough therapy designation and/or fast track designation from the FDA to support potentially expedited regulatory pathways in the U.S. for [Mytesi] for this indication."

The FDA, as the agency explains on its website, has the authority to grant orphan drug designation to a drug or biological product that could be used to prevent, diagnose or treat a rare disease or condition. In turn, orphan drug designation qualifies sponsors for incentives such as tax credits, exemption from user fees and, if approved, potentially seven years of market exclusivity.

Mytesi has already received orphan drug designation in the United States for short bowel syndrome with intestinal failure and microvillus inclusion disease for a liquid formulation of the treatment, and it has also been granted an orphan drug designation for treatment of diarrhea in cholera in the U.S.

Mytesi, as explained in the news release, is a plant-based drug extracted and purified from the red bark sap of the medicinal Croton lechleri tree found in in the Amazon rainforest. Mytesi, according to the product’s website, is designed to work by restoring the balance of salts and water in the gut, normalizing the flow of water and resulting in less watery diarrhea.

Mixed results from the OnTARGET clinical trial

It was previously found that prophylaxis with Mytesi did not lead to a statistically significant improvement in the incidence of diarrhea versus placebo among adult patients with solid tumors who were being treated with targeted therapy with or without chemotherapy, hence missing the primary endpoint of the phase 2 OnTARGET clinical trial, as reported in 2024 by OncLive, a sister publication of CURE. But, it was noted that the time that a subgroup analysis also showed that clinically relevant signals for Mytesi were reported among patients with breast and respiratory cancers, including lung cancer.

“We believe the OnTARGET trial, designed boldly to address a broad array of [patients with] cancer undergoing therapy known to be associated with diarrhea, did not meet the primary end point given the heterogenous nature of the patients enrolled in the trial. Nevertheless, we are pleased that our preliminary analysis of the study data shows a clinically meaningful benefit in response to [Mytesi] in patients with breast and respiratory cancers, including lung cancer,” Lisa Conte, founder, president, and chief executive officer of Jaguar Health, stated in a news release.

“Breast and lung cancer are two of the top three most common cancer types, and treatment options for breast and lung cancer include the long-term use of targeted therapies that cause high incidences of diarrhea,” Conte continued. “We will continue to review data from prespecified and non-prespecified OnTARGET subgroups and then engage in discussions with the FDA to seek the most efficient pathway to bring [Mytesi] to these patients and address the important and debilitating side effect of cancer therapy–related diarrhea with the paradigm shifting mechanism of [Mytesi]. Patient dignity and the ability of patients to adhere with comfort to their cancer therapy is first and foremost in our ongoing development efforts."

References

1. “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,” news release; https://jaguarhealth.gcs-web.com/news-releases/news-release-details/jaguar-health-submits-orphan-drug-designation-application-fda
2. “How Does Mytesi Work?,” https://mytesi.com/how_mytesi_works/
3. “Crofelemer Misses Diarrhea End Point in Patients With Solid Tumors Receiving Targeted Therapy,” OncLive; https://www.onclive.com/view/crofelemer-misses-diarrhea-end-point-in-patients-with-solid-tumors-receiving-targeted-therapy

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