Arena Pharmaceuticals Reports Topline Results from Atopic Dermatitis Trial

Arena Pharmaceuticals announced topline results from the Phase 2b ADVISE clinical trial evaluating etrasimod, a highly selective, once-daily, oral sphingosine 1-phosphate (S1P) receptor modulator, for the treatment of moderate-to-severe atopic dermatitis (AD).

"Today is an important day for Arena as we achieved our key objectives for the ADVISE trial which were to evaluate safety and efficacy of etrasimod in a dermatologic population, and to inform dose and design decisions for a pivotal Phase 3 program. 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," said Chris Cabell, MD, MHS, FACC, Executive Vice President, Head of Research and Development, and Chief Medical Officer at Arena. "We look forward to advancing etrasimod into a Phase 3 program in atopic dermatitis. We would like to thank the patients, trial coordinators and investigators who participated in this important trial."

In the ADVISE trial, the participants were representative of a moderate patient population (82.9% baseline vIGA 3) which constitutes upward of 40% of the AD market. In the primary analysis, 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. Importantly, 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 4. Etrasimod did not meet the Ph 2b primary endpoint of EASI change from baseline at week 12 as compared to placebo.

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% (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.

Importantly, 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.

Based on the compelling profile in this moderate AD population, etrasimod will be proceeding into a Phase 3 registrational program.

"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," said 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," said 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.