Arena Pharmaceuticals announced positive topline results from its Phase 2a trial of olorinab, an investigational, peripherally restricted, highly selective, full agonist of the cannabinoid receptor 2 (CB2) in development for the treatment of gastrointestinal pain.
This was a randomized, open-label, 8-week study investigating two doses of olorinab (25 mg and 100 mg) administered TID (three times daily). All patients were diagnosed with quiescent to mild active Crohn's disease associated with chronic abdominal pain defined as a baseline Average Abdominal Pain Score (AAPS) ≥4. Fourteen patients were enrolled with a mean baseline AAPS of 5.6.
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Reductions in pain were seen within the first week of treatment with olorinab and statistically significant improvement from baseline in AAPS was observed at weeks 4 and 8. In the 11 patients evaluable at 8 weeks of treatment (baseline AAPS of 6.0), there was an improvement in AAPS of -4.6 (p<0.001) from baseline at peak effect (1.5 hours post morning dose). At peak effect, 11 out of 13 patients (85%) with evaluable data at week 4, and 11 out of 11 patients (100%) with evaluable data at week 8, exhibited a clinically relevant improvement (≥30% change from baseline) in AAPS. Results in all patients randomized (intent-to-treat) demonstrated 11 out of 14 patients (79%) with clinically relevant improvement at both weeks 4 and 8. The improvement in pain was consistent at both the 25 mg and 100 mg olorinab dose levels and a statistically significant improvement in AAPS was also observed at trough levels (before the morning dose).
Olorinab appeared safe and generally well tolerated in this study with no clinically significant changes in heart rate or blood pressure, no psychotropic effects, and no discontinuations due to adverse events.
"There is a strong clinical need for non-opiate treatments for the management of chronic abdominal pain in patients with gastrointestinal disorders, including Crohn's disease, ulcerative colitis and irritable bowel syndrome," said Bruce Yacyshyn, MD, Professor Medicine in the Division of Digestive Diseases at the University of Cincinnati College of Medicine and Medical Director for Inpatient Gastroenterology at UC Health University Hospital. "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 GI pain. I look forward to the further development of this interesting compound as an aid in the management of this complex group of patients."
"The intent of this Phase 2a study of olorinab was to get directional information on the safety, tolerability and therapeutic potential to reduce gastrointestinal pain in patients with Crohn's disease and symptoms of chronic abdominal pain,” Preston Klassen, MD, MHS, Chief Medical Offer of Arena, said. “Despite its small size and uncontrolled design, 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. We look forward to providing additional detail on the development path forward during Arena's R&D Day on October 4th."