What to Know: Phase 3 Findings on Promising Psoriasis Pipeline

Mark G. Lebwohl, MD, presents on what dermatologists need to know about the newest psoriasis studies during the Fall Clinical Dermatology Conference.

Phase 3 trial results suggest 3 psoriasis drugs—2 topicals and 1 oral—are promising investigational treatments and, if FDA approved, could become important options for patients, according to Mark G. Lebwohl, MD, professor of dermatology at Mount Sinai, New York, New York. Lebwohl presented on the newest psoriasis studies during the October 21-24 Fall Clinical Dermatology Conference in Las Vegas, Nevada.1

PSOARING 1 and PSOARING 2 are identically designed studies looking at use of tapinarof cream (GSK2894512; Dermavant), a once-daily topical aryl hydrocarbon receptor (AhR) agonist.

The 12-week, double-blind, placebo-controlled tapinarof trials show 20% of patients with mild disease; 40% with moderate plaque psoriasis; and 36% with severe disease responded to the topical.

Body surface area impacted—whether more or less than 10%—did not affect results, with more than 35% of patients responding to tapinarof, according to Dr. Lebwohl.

“Whether the patient had psoriasis for less than 5 years, 5 to 10 years or more than 10 years, the response rate fell between 35% and 39%,” Lebwohl said. “Males and females responded similarly. Interestingly, patients older than 65 responded a little bit better than younger patients. Of the responders, the proportion of patients that were clear were 40.9%, the proportion of patients that were clear or almost clear with a 2-grade improvement was 58%.”

Topical roflumilast (ARQ-151; Arcutis Biotherapeutics), a phosphodiesterase-4 (PDE4) enzyme inhibitor, was shown in phase 3 research to be highly effective and comparable to strong steroids for psoriasis, according to Lebwohl.

“Roflumilast was effective to an extraordinary degree for intertriginous psoriasis. This is a badly needed option for patients. We don’t like using steroids in the body folds, the groin, the armpits … so we need a nonsteroid medication, and it turns out roflumilast showed high efficacy in those sites,” he said.

Oral deucravacitinib (BMS-986165; Bristol-Myers Squibb) is a tyrosine kinase 2 (TYK2) inhibitor.

“Deucravacitinib is considered a janus kinase (JAK) inhibitor, but unlike the other JAK inhibitors which can cross react with one another because they bind to a common binding site on the janus kinase molecule, this one does not,” Lebwohl said. “This molecule binds to the regulatory domain of TYK2.”

Because the other JAK inhibitors bind to an ATP binding active site, they share certain side effects. Deucravacitinib appears to avoid those side effects, he said.

In 1 phase 3 study, more than half (53%) of psoriasis subjects taking deucravacitinib achieved a psoriasis area and severity index (PASI) 75. More than 58% achieved PASI 75 in another study. About half of those studied were clear or almost clear, according to Lebwohl.

“This is an oral molecule, which is an advantage over injections. It also works fairly quickly. Most of the benefit is in the first 4 weeks,” Lebwohl said. “Deucravacitinib is expected to be approved during 2022.”

In another update, Lebwohl noted that bimekizumab (BIMZELX; UCB), the first dual inhibitor of interleukin (IL)-17A and IL-17F for the treatment of psoriasis, was supposed to be approved in mid-October 2021. However, because of the pandemic, the FDA had to put off its investigation of the drug’s manufacturing facilities.2

“Bimekizumab is the first biologic we have that in placebo-controlled period of the pivotal trials gave PASI 100 to a majority of patients at the primary endpoint,” he said. “It is also very fast and durable.”

Disclosures:

Lebwohl is an employee of Mount Sinai and receives research funds from Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research & Development, Leo Pharmaceuticals, Ortho Dermatologics, Pfizer, and UCB, and is a consultant for Aditum Bio, Allergan, Almirall, Arcutis, Avotres Therapeutics, BirchBioMed, BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr Reddy’s Laboratories, Serono, Theravance, and Verrica.

References:

  1. Del Rosso J, Desai S, Lebwohl M. Clinical dermatology: what you need to know about the newest studies. Fall Clinical Dermatology Conference; October 21, 2021; Las Vegas and virtual.
  2. Reis J, Vender R, Torres T. Bimekizumab: the first dual inhibitor of interleukin (Il)-17a and il-17f for the treatment of psoriatic disease and ankylosing spondylitis. BioDrugs. 2019;33(4):391-399. doi: 10.1007/s40259-019-00361-6