Phase III OnTarget trial results announced for crofelemer in prophylaxis of diarrhea for cancer supportive care

Crofelemer is an FDA-approved prescription drug for the symptomatic relief of diarrhea in adult HIV/AIDS patients receiving antiretroviral therapy. The initial results from the OnTarget study show that the multicenter, double-blind, placebo-controlled pivotal clinical trial did not meet its primary endpoint for the prespecified analysis of all tumor types in the trial.

"While the results of the OnTarget study did not achieve significance for all tumor types receiving various targeted therapies, I am pleased that the subgroup analyses show that crofelemer provides clinically meaningful improvement in the prespecified subgroups of breast and respiratory tumor patients. Clinical meaningfulness of these results is based on the information provided by solid tumor patients from a survey that informed us about the appropriate clinical study design and clinical endpoints, that are important to the patients in this prophylactic trial. We will continue to evaluate important OnTarget findings, with further analyses," said Pablo Okhuysen, MD, Professor of Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, who is the Principal Investigator of the OnTarget clinical trial. "It is important to note that the prespecified secondary outcomes for this study were based on outcomes that were considered to be meaningful by patients experiencing diarrhea due to targeted therapy."

Key Take-a-ways from the ONTARGET trial: i. Unprecedented OnTarget trial included patients with 10 different tumor types and 24 different targeted agents, with and without multiple standard cytotoxic chemotherapies. ii. Study did not meet prespecified analysis of primary endpoint for all tumor types. iii. Analysis did reveal clinically relevant signals for patients in the prespecified subgroups of breast and respiratory cancers, including lung cancer, who received targeted therapies. These subgroups of patients comprised over 75% of the patients in the trial. iv. Breast and lung cancers are two of the three most common cancers, with patients often remaining on targeted therapy over prolonged periods. v. A growing and urgent unmet medical need exists for novel non-opioid chronic agents to treat CTD. vi. Results indicate positive signals improved over the initial 12-week phase of study; vii.data for additional 12-week extension phase yet to be analyzed. viii.Company expects to engage with FDA after full review of data.

The unprecedented OnTarget trial included patients with 10 different tumor types and 24 different targeted agents, with and without multiple standard cytotoxic chemotherapies. It consisted of two 12-week stages: a 12-week double-blind treatment phase followed by a 12-week double-blind extension phase. The prespecified primary endpoint for the trial was defined as reducing the average number of weekly loose and/or watery stools for all tumor types receiving various targeted therapies over the initial 12-week period of this prophylactic study. Analysis of data for the initial 12-week stage revealed clinically relevant signals for crofelemer over placebo in the prespecified subgroups of breast and respiratory cancer patients, who comprised over 75% of the patients in OnTarget, and it appears that this benefit improved over the initial 12-week stage. The data for the study's 12-week extension phase has not yet been analyzed. The company will complete the analysis of full data for the first and second 12-week periods and will disclose the results in future presentations and publications.

Crofelemer was well tolerated in OnTarget, and the adverse event profile was similar to placebo. Most adverse events were related to the cancer therapy and/or the disease itself. The OnTarget findings are based on 287 patients representing all solid tumor types and 24 targeted agents, with or without cytotoxic chemotherapy. Included within the 287 enrolled patients were 37 respiratory cancer patients and 180 breast cancer patients or greater than 75%. The patients were enrolled from 49 sites and included investigators from oncology clinics in the United States, Argentina, Georgia, Serbia, and Taiwan.