A study in dogs has shown that crofelemer can provide symptomatic relief of diarrhoea associated with the irreversible pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor (TKI) neratinib (Nerlynx).
Puma Biotechnology’s Nerlynx is a pan HER TKI indicated for the extended adjuvant treatment of adult patients with early stage and metastatic HER2 positive breast cancer.
The study was conducted by Jaguar company Napo Pharmaceuticals in collaboration with Puma Biotechnology.
Cancer therapy-related diarrhoea (CTD) has the potential to cause dehydration, infections and non-adherence to treatment, and is a growing unmet medical need in cancer patients.
“We are very pleased with the results of this prophylactic study, which was undertaken to ‘model’ the human situation with neratinib,” said Lisa Conte, Jaguar’s President and CEO. “Crofelemer, our novel, oral, plant-based, non-opioid antidiarrhoeal prescription medication, is also the subject of OnTarget, Jaguar’s pivotal Phase III clinical trial for the follow-on indication of the preventative treatment of CTD, an indication we also refer to as chemotherapy-induced overactive bowel (CIOB).”
Dr Michael Guy, Jaguar’s Vice President of Preclinical and Nonclinical Studies, added: “The study demonstrated that crofelemer caused an approximate 30% reduction in the incidence and severity of diarrhoea associated with daily oral administration of neratinib, which was statistically significant.”
In a pilot Phase II study in humans, seven patients underwent treatment with crofelemer and loperamide, five of whom were able to control diarrhoea with crofelemer alone.
“Though this study involved a small number of patients, the results show activity of crofelemer for the management of neratinib-induced diarrhea, which warrants further investigation of crofelemer for treatment of cancer therapy-related diarrhea (CTD),” said study investigator Hope Rugo, Professor of Medicine and Winterhof Family Professor of Breast Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.