Preston Klassen, MD, head of research and development at Arena Pharamaceuticals, discusses mucosal healing and histologic remission in patients with ulcerative colitis receiving etrasimod.
A recent phase 2 study found that patients with ulcerative colitis receiving etrasimod saw greater rates of histologic remission, endoscopic improvement, and histologic improvement compared to patients receiving placebo.
The results of the randomized, placebo-controlled study were presented at Digestive Disease Week 2019. Preston Klassen, MD, executive vice president and head of research and development at Arena Pharmaceuticals, sat down with MD Magazine® to discuss the findings of that study and the impact of etrasimod on mucosal healing and histologic remission in patients with moderate to severely active ulcerative colitis.
MD Mag: What were the findings of your study into use of etrasimod in patients with moderately to severely active ulcerative colitis?
Klassen: So, this year at DDW we had a variety of analyses and poster presentation talking about both etrasimod and olorinab. One of the oral presentations was presented by Dr. Peyrin-Biroulet and he presented data on histologic remission and mucosal healing coming out of our phase 2 OASIS trial in patients with ulcerative colitis being treated with etrasimod. This is a secondary analysis of that OASIS trial and in that trial, which was about 150 patients — 50 per arm, roughly — 2 doses of etrasimod 1mg and 2mg and a placebo control group and the primary clinical end points from that phase 2 study were related to the Mayo Clinic score, either the 4 domain full total Mayo score or a modified 3 domain a total Mayo score. The primary results showed statistically significant and clinically meaningful improvements in both clinical remission and clinical response over 12 weeks of dosing.
So, this secondary analysis took an additional step further and looked at the more objective endpoints of endoscopic improvement or remission and histologic improvement or remission and then combined the 2 of them into a mucosal healing score. So, the analyses showed that both endoscopic improvement and remission and histologic improvement in remission and this histologic was analyzed out of tissue biopsies that were taken during study using the Gebos scale and so there's specific definitions for what constitutes improvement at a tissue level or remission at a tissue level and then what constitutes improvement at an endoscopic level.
So, we saw statistically significant and clinically meaningful improvements across all those, particularly the 2mt dose which is the highest dose tested. Then, when you combine them in terms of mucosal healing we saw that 20% of patients compared to 4% of patients in the placebo group 20% at 2mg demonstrated mucosal emission, which was defined as endoscopic improvement with histologic remission. So, overall these results are encouraging in terms of the very most objective measure of what the drug might be doing looking both at the tissue and at a more macro level at the endoscopic findings