Phase 2 Trial Setback of Investigational IBS Drug Prompts Arena to Ponder Strategic Alternatives

On March 2nd, Boston-based Arena Pharmaceuticals announced that Olorinab, a treatment for abdominal pain due to Irritable Bowel Syndrome (IBS), failed to meet its primary endpoint in a Phase 2b Trial. However, at the highest concentration tested, Olorinab provided a significant reduction in abdominal pain in patients with moderate to severe pain. In light of the news, at the end of the trading session, Arena’s stock had declined 4.62%, a larger loss than the -3.58% in the iShares Nasdaq Biotechnology ETF.

IBS is a common disorder that affects between 25-45 million people in the US. It is characterized by cramping, abdominal pain, and chronic diarrhea, constipation, or both. There is no cure for this disease, but several medications to manage the symptoms are available. However, not all treatments work for everyone, for this reason, new treatments are necessary to meet the need.

CAPTIVATE Trial

Olorinab is an orally available agonist of the cannabinoid receptor 2 (CB2). Its selectivity against the CB2 receptor could provide pain relief while minimizing the risk of psychoactive effects. Its efficacy and safety were determined on the multi-center, randomized, double-blind, placebo-controlled, Phase 2b CAPTIVATE trial.

Three different concentrations of Olorinab, 10 mg, 25 mg, and 50 mg, were tested. The study’s primary endpoint was to determine if Olorinab reduced pain in patients after 12 weeks compared to control. Changes in pain were measured using the Average Abdominal Pain Score (AAPS).

Results demonstrated that Olorinab failed to provide a significant reduction in AAPS in patients after 12 weeks. However, in a subgroup of patients with moderate to severe pain, Olorinab treatment resulted in a significant reduction in AAPS at the highest concentration, 50 mg. In addition, Olorinab was well tolerated, and no serious adverse events occurred.

“The CAPTIVATE study was the first study to examine a full agonist of CB2 in IBS pain. As a Phase 2 trial, we were evaluating safety in this population as well as looking for an initial signal of efficacy,” said Paul D. Streck, MD, Arena’s Senior Vice President, Clinical Development, and Chief Medical Officer. “We are encouraged by the signal in this moderate to severe group and look forward to sharing the full data from this well-executed trial at an upcoming medical meeting.”

Targeting the Cannabinoid System for Pain Relief

Targeting the cannabinoid system has been shown to be a viable option for treating chronic pain, chronic inflammation, and autoimmune diseases. Furthermore, specifically targeting the cannabinoid receptor 2 (CB2) has been shown to reduce pain and inflammation while avoiding any psychoactive effects. It has also been proposed as an alternative to opioids to treat chronic pain.

Apart from Olorinab, there are at least two more CB2 agonists currently in clinical trials. Lenabasum from Corbus Pharmaceutical for the treatment of autoimmune disease and cystic fibrosis, and CNTX-6016 from Centrexion Therapeutics to treat neuropathic pain.

Amit Munshi, President and Chief Executive Officer at Arena, said they expect to evaluate possible strategic options for Olorinab, including repurposing the drug for autoimmune diseases or other types of pain.

Related Article: Neurocrine, Takeda Look to Build on Positives Post Luvadaxistat’s Schizophrenia Trial Failure

Author

Daniel Ojeda