Olorinab, an investigational compound being developed by Arena Pharmaceuticals, significantly reduced chronic abdominal pain in patients with Crohn’s disease, according to topline results from a Phase 2a clinical trial. The findings also revealed a positive safety profile.
Olorinab (APD371) is an oral, highly selective agonist of the cannabinoid receptor 2 (CB2) being developed as a therapy for visceral pain associated with gastrointestinal diseases, including Crohn’s.
Prior preclinical studies in models of chronic pain, including inflammatory bowel disease (IBD), indicated that olorinab has sustained efficacy. In addition, Phase 1 results revealed that the therapy is safe and well-tolerated.
The randomized, open-label trial (NCT03155945) examined the effects of a 25 or 100 mg dose of olorinab three times daily in 14 patients with quiescent (inactive) to mild active Crohn’s disease and chronic abdominal pain. All patients had a minimum initial average abdominal pain score of 4.
The trial’s primary goal was to determine the therapy’s safety over the eight-week treatment period. Secondary measures included the biological fate of olorinab, change in pain score, number of weekly responders — participants with a 30% or greater decrease in average abdominal pain score — and number of pain-free days, among others.
Olorinab’s impact on Crohn’s inflammatory markers and patient-reported outcomes/health questionnaires were also assessed.
Patients experienced a reduction in pain within the first week of treatment, and had significantly lower pain scores at the fourth and eighth weeks. The 11 patients with data able to be evaluated at week eight showed a 4.6 decrease from initial values in their average pain scores.
When olorinab was at its peak effect, 11 out of 13 patients (85%) with evaluable data at week four and all 11 patients at week eight revealed a clinically relevant improvement (30% or greater change from initial values) in their pain scores.
Importantly, pain reduction was similar between the 25 and 100 mg dose levels, and a significant decrease in pain scores was also observed when oloripab was at its lowest levels.
Olorinab treatment was safe and generally well-tolerated, with no clinically significant changes in heart rate or blood pressure, no psychotropic effects — in agreement with a Phase 1 study in healthy volunteers, indicating no risk of abuse or dependence — and no discontinuations due to adverse events.
“The exciting results from this initial Phase 2a study in patients with Crohn’s disease leaves me optimistic for the potential of olorinab as a novel approach for the management of [gastrointestinal] pain,” Bruce Yacyshyn, MD, a professor of digestive diseases at the University of Cincinnati College of Medicine, said in a press release.
Noting the strong medical need for non-opiate treatments for chronic abdominal pain in Crohn’s and ulcerative colitis — the two main forms of IBD — as well as in irritable bowel syndrome, Yacyshyn, also the medical director for inpatient gastroenterology at UC Health University Hospital, added that he looks forward “to the further development of this interesting compound as an aid in the management of this complex group of patients.”
“This trial provides early results that suggest a robust clinical response and supports continued, rapid development of olorinab, potentially targeting several diseases in which gastrointestinal pain is a hallmark.” said Preston Klassen, MD, Arena’s chief medical officer. However, he also mentioned the study’s small size and lack of controls.
“We look forward to providing additional detail on the development path forward during Arena’s R&D Day on October 4th,” Klassen said.
Besides olorinab, Arena is also developing etrasimod (APD334), which is expected to start a Phase 3 program for ulcerative colitis and a program for Crohn’s disease. The investigational therapy could be used in a wide range of immune and inflammatory conditions, according to the company.