Novel S1P-Receptor Modulator Shows Promise in Phase 2b AD Trial

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A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Guttman-Yassky said. “I think the data will be even better in a longer study.”

In regard to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Guttman-Yassky is a paid consultant and researcher for Arena.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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