Nearly one-third of participants in the 2 mg etrasimod group achieved clear or almost clear skin, as defined by the validated Investigator Global Assessment (vIGA), the FDA endpoint for Phase 3 registration, according to topline results from Arena’s Phase 2b ADVISE clinical trial evaluating etrasimod for the moderate-to-severe atopic dermatitis (AD).
Moreover, the vIGA improvement was statistically significant vs. placebo at 12 weeks
Across the Eczema Area and Severity Index (EASI), EASI-75 and peak change in pruritis, etrasimod 2 mg demonstrated early and statistically significant effect at week four, but Etrasimod did not meet the Ph 2b primary endpoint of EASI change from baseline at week 12 as compared to placebo, the study showed. Etrasimod will be proceeding into a Phase 3 registrational program.
Overall, the 12-week study showed no plateau of effect, and the safety profile was consistent with previous trials of etrasimod including low first dose heart rate effect with no titration, and no serious adverse events (SAEs) across the groups. In the etrasimod groups, there were no cases of venous thromboembolic events, opportunistic or serious infections, macular edema, conjunctivitis, acne or herpes zoster. Additionally, none of the other adverse events commonly associated with first-generation S1P receptor modulators were seen in this trial.
Between weeks 4-8, the trial was impacted by unwarranted dose interruption (not related to drug safety) in 19 percent (n=9) of the etrasimod 2 mg group. Adjusting for this dose interruption – a post-hoc Completer Analysis with participants receiving full therapeutic exposure – etrasimod 2 mg showed statistically significant effect on the EASI score compared to placebo (weeks 4 and 12), EASI-75 at week 4, vIGA at week 12 and pruritis through week 8.
The analysis of the participant cohort with dose interruption showed diminished clinical effect upon withdrawal and a recapture of effect upon reinstatement of study drug consistent with the pharmacodynamics (PD) of etrasimod.
"We believe the clinical benefits of etrasimod in this trial were impressive, especially given the challenges of conducting a Phase 2 trial with a novel MOA in atopic dermatitis," states Chris Cabell, MD, MHS, FACC, Executive Vice President, Head of Research and Development, and Chief Medical Officer at Arena, in a news release. "We look forward to advancing etrasimod into a Phase 3 program in atopic dermatitis."
"I was encouraged by etrasimod's ability to demonstrate early differentiation from placebo and continued improvement to week 12 and a favorable safety profile. These data support moving forward to the next stage of clinical development," says Emma Guttman, MD, PhD, Sol and Clara Kest Professor and the Incoming Chair at the Department of Dermatology, Director of the Center for Excellence in Eczema, and Director of the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.
"The results of the ADVISE trial are promising. In particular the efficacy as measured by improvement in vIGA will be important in determining the dose and design of the Phase 3 registrational program," adds Jonathan I. Silverberg, MD, PhD, MPH, Associate Professor of Dermatology, Director of Clinical Research, and Director of Patch Testing, at the George Washington University School of Medicine and Health Sciences.
Arena plans to submit additional data from the ADVISE trial to future medical meetings and for publication in a peer-reviewed journal.