Stay tuned for an exciting new module of Xtalks.com. We have also made a minor change to our updated privacy policy.

X

Arena Pharmaceuticals’ Selective CB2 Receptor Activator Drug Candidate Fights Pain in Irritable Bowel Syndrome

Arena Pharmaceuticals’ Selective CB2 Receptor Activator Drug Candidate Fights Pain in Irritable Bowel Syndrome

As olorinab advances through clinical testing, it may become the first drug to specifically relieve pain in people with irritable bowel syndrome.

Update (June 20, 2019): Earlier this week, Arena Pharmaceuticals announced the first patient has been dosed in the ELEVATE UC 52 trial, one of two pivotal trials in a Phase III program for etrasimod. One of etrasimod’s functions is to modulate immune cell trafficking, imparting some anti-inflammatory properties to the drug. If the Phase III program is successful, etrasimod will be Arena’s first internal drug candidate to advance into the market.

Dr. Preston Klassen, MHS, Executive Vice President of Research and Development Chief Medical Officer of Arena tells Xtalks more about the study:

“We are encouraged by the etrasimod data seen to date, which have provided important insights for the design of the ELEVATE UC pivotal program, giving us confidence that it will demonstrate clinically meaningful and market-leading evidence of efficacy and safety. The initiation of the ELEVATE UC 52 trial, which will be conducted in approximately 450 sites across more than 40 countries, brings us one step closer to delivering this novel, oral therapy to ulcerative colitis patients globally.”


Originally published on June 5, 2019: 

For about 12 percent of the world’s population living with the bowel movement disorder, irritable bowel syndrome, abdominal pain is a part of everyday life. While there are drugs available to treat symptoms like constipation and diarrhea, there is one complication that few irritable bowel syndrome drugs treat effectively.

“What’s common to all irritable bowel syndrome patients is the presence of abdominal pain, and it is probably the aspect of the condition that is most difficult to treat,” said Dr. Preston Klassen, Head of Research and Development and Chief Medical Officer at Arena Pharmaceuticals.

To treat abdominal pain, people with irritable bowel syndrome might take over-the-counter medication or prescription opioid for quick relief. But the high abuse potential of opioids and current epidemic in the US is triggering a search for non-opioid pain therapy alternatives.

Scientists at Arena Pharmaceuticals are hoping to address abdominal pain through a novel mechanism by targeting cannabinoid type 2 receptor (CB2) receptors.

“CB2 receptors are highly expressed in the gut and they are upregulated in GI conditions such as inflammatory bowel disease and irritable bowel syndrome,” explained Klassen in an interview with Xtalks.

These cannabinoid receptors should not be confused with CB1, the ones primarily associated with psychoactive effects such as euphoria of cannabis-based medications. In developing drugs that affect the endocannabinoid system, it’s important to make them as specific as possible to its target.

“Our compound is very specific to peripheral CB2 receptors and seems to predominantly impact pain fibers in the intestines,” said Klassen.

The company’s oral, peripherally-acting CB2 agonist, olorinab, has shown efficacy in preclinical and early clinical studies. In a Phase IIa study, patients with Crohn’s disease, a type of inflammatory bowel disease, reported a 30 percent or greater reduction in abdominal pain scores from baseline after eight weeks of olorinab therapy. These patients had mildly active Crohn’s disease but still exhibited daily abdominal pain, making the trial more of an examination of pain control rather than resolution of active inflammation. In preclinical studies of osteoarthritis or diabetic neuropathy, olorinab showed similar analgesic potential as morphine or gabapentin.

In conducting pain studies, researchers should factor in the placebo effect — a clinical response that arises from expectations of the patient rather than from the effects of the treatment. No placebo group was involved in this initial Phase IIa study, but Klassen says the magnitude of response is “unlikely due to chance or placebo, given the magnitude and consistency of the response.”

Moving forward, the company plans to begin a placebo-controlled Phase IIb trial later this year in patients with irritable bowel syndrome experiencing uncontrolled abdominal pain. As olorinab advances through clinical testing, it may become the first drug to specifically relieve pain in people with irritable bowel syndrome.

“We need to do our work to move into irritable bowel syndrome and understand the ability of the drug to impact pain,” said Klassen. “Everything we see today preclinically and clinically suggests that [olorinab] may have a high degree of analgesic activity in conditions like Crohn’s and irritable bowel syndrome.”

The anti-diarrheal drug Lotronex (alosetron) and the anti-constipation drug Linzess (linaclotide) are prescribed in irritable bowel syndrome predominantly for their effects on intestinal motility. Although these drugs may also have some effects on abdominal pain relief, Klassen believes that there is ample room for additional therapies targeting abdominal pain. He notes that to date, the evidence is strongest for the analgesic effects of olorinab, with little evidence for effects on intestinal motility or inflammation — eventually, it can potentially be used together with other remedies.

“Patients with irritable bowel syndrome can end up taking laxatives to control some of the motility issues or bulk fiber to control some of the diarrhea aspects,” he continued. “But everyone affected, by definition, has pain and could potentially benefit from a novel, effective and safe pain product. [Olorinab] can be an add-on therapy where needed.”

In addition to olorinab, Arena Pharmaceuticals is also investigating its oral, selective sphingosine 1 phosphate (S1P) receptor modulating drug candidate, etrasimod, due to be evaluated in a global Phase III ulcerative colitis study, a Phase IIb/III Crohn’s disease study, and Phase II atopic dermatitis study.


Preston Klassen
Dr. Preston Klassen, Head of R&D & CMO, Arena Pharmaceuticals