Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) today announced data at a late-breaking session at the American Academy of Dermatology VMX Experience. Etrasimod, a novel investigational drug candidate to treat moderate-to-severe atopic dermatitis (AD), demonstrated statistical significance in both clinician and patient reported outcomes in the ADVISE Phase 2b clinical trial. Etrasimod is a highly selective, once-daily, oral sphingosine 1-phosphate (S1P) receptor modulator. Today’s results are presented by Emma Guttman-Yassky, MD, PhD, Waldman Professor and Chairwoman, The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai.
“Etrasimod demonstrated clinically meaningful improvements in both clinical signs of atopic dermatitis and patient reported outcomes,” Dr Guttman said. “Additionally, patient reported outcomes were improved as early as 2 weeks after etrasimod treatment was initiated. Combined with a favorable safety profile, these results are promising for this new mechanism of action for the treatment of atopic dermatitis.”
In the ADVISE trial, Arena Pharmaceuticals evaluated the safety and efficacy of etrasimod in participants with moderate to severe eczema as well as to gain insight into design parameters for a potential pivotal Phase 3 program. Additionally, Arena quantified participants’ assessments of etrasimod’s efficacy using the peak pruritis numeric rating scale (PP-NRS), Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM). Given the statistically significant and clinically meaningful improvements in PROs coupled with the statistically significant improvements shown on the clinician-observed vIGA scale, Arena Pharmaceuticals expects to advance etrasimod into a pivotal registrational Phase 3 program for atopic dermatitis.
“The results reported today by Dr. Guttman-Yassky from the ADVISE trial have demonstrated impressive clinical benefit for patients living with moderate to severe atopic dermatitis,” said Paul D. Streck, MD, Senior Vice President, Clinical Development, and Chief Medical Officer. “Together with a favorable safety profile, both the clinician-based assessments and the patient reported outcomes provide a strong basis to advance etrasimod to a global Phase 3 program as a potential treatment for atopic dermatitis. If approved, etrasimod has the potential to bring a novel, easily dosed oral therapy to patients who currently face limited treatment options for this chronic and debilitating disease.”
Discussion of Trial
In the trial, 140 participants with chronic, moderate to severe eczema for at least a year were randomized into three equal cohorts for etrasimod 1 mg, etrasimod 2 mg, and placebo, treated once daily for 12 weeks. At the start of the trial, participants showed an Eczema Area and Severity Index (EASI) equal to or greater than 16, a vIGA score equal to 3 or more, and were affected by AD over 10% or more of their body surface. Of the etrasimod 2 mg participants, 29.8% successfully reduced their clinician-reported vIGA at 12 weeks to 0 or 1 (representing “clear” or “almost clear” skin) and improved by at least 2 points, compared to 13% for placebo (p=0.0450).
ADVISE also included three dermatology-specific patient reported outcomes. Participants gave regular evaluations of their peak pruritis numeric rating scale (PP-NRS), Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM).
- For the PP-NRS, individuals in the etrasimod 2 mg cohort showed a statistically significant improvement as early as Week 2, compared to placebo, in their PP-NRS percentage score from baseline at the start of the trial; the etrasimod 2 mg cohort reported peak pruritis dropped 15.3% compared to a drop for placebo of only 1.0% (p=0.0380) at Week 4. This early dramatic drop suggests a rapid onset of action for etrasimod. The PP-NRS also dropped numerically a greater amount at Week 12 for the etrasimod 2 mg cohort (34.1%) than for the placebo cohort (23.9%) (p=0.1549).
- The DLQI measures overall impairment due to a dermatologic condition on a scale of 0 to 30, with 30 representing an extremely large effect on a patient’s life. In assessing their overall DLQI, participants in the etrasimod 2 mg cohort saw statistically significant declines in their degree of impairment, dropping 7.6 points at Week 12 versus a drop of 4.2 points for placebo (p=0.0122).
- The POEM patient-reported measure of etrasimod’s efficacy also validated the investigational drug as a potential treatment for AD. The indexing of POEM indicates that as disease severity is reduced, the patient’s life improves. In ADVISE, the etrasimod 2 mg cohort experienced an 8.4 point reduction versus 4 points for placebo (p=0.0045), results that are both clinically and statistically significant.
Etrasimod showed a favorable safety profile in ADVISE. During the trial there were no serious adverse events or opportunistic or serious infections observed. The most common adverse events for participants of >5% and greater than placebo were nausea, constipation, back pain and dizziness.
Arena plans to submit data from the ADVISE trial for publication in a peer-reviewed journal.
Dr. Guttman-Yassky is a paid consultant and researcher for Arena Pharmaceuticals.