Recent interest in developing treatments for atopic dermatitis (AD) has created a cornucopia of new and pending product approvals, according to an expert at the 75th American Academy of Dermatology Annual Meeting, Orlando, Fla.
"Unlike the last decade," says Eric Simpson, M.D., "we finally have a lot to talk about in atopic dermatitis therapy. There's lots of interest and activity in developing new therapies for this disease." He is a professor of dermatology at Oregon Health Sciences University.
Researchers and investors are realizing the seriousness of AD and its high impact on many patients' quality of life, he says.
"And we're understanding the pathophysiology of the disease better. Companies are starting to take notice – finally," he adds.
Most recently, a phase 3 study of the novel phosphodiesterase (PDE) 4 inhibitor crisaborole showed that twice-daily application of crisaborole ointment for 28 days allowed 32.8% and 31.4% of treated patients in separate studies to achieve the primary endpoint, an Investigator's Static Global Assessment (ISGA) score of zero (clear) or 1 (almost clear) with 2-grade or greater improvement from baseline.1 The corresponding figures among placebo-treated patients were 25.4% and 18%, respectively (P = 0.038, P<0.001, respectively). Moreover, among patients who met the primary endpoint, the majority (51.7% versus 40.6% placebo, and 48.5% versus 29.7%; P = 0.005, P<0.001, respectively) were clear. Crisaborole-treated patients also achieved success in ISGA and pruritus scores earlier than those treated with placebo.
Approval of crisaborole by the U.S. Food and Drug Administration (FDA) in December 2016 has brought a new nonsteroidal treatment to the market, says Dr. Simpson, a pivotal study investigator.
"The biggest question is, will this replace other nonsteroidal eczema treatments like topical calcineurin inhibitors (TCIs) in terms of payer coverage? It's still unclear where it falls in the treatment paradigm. It's a safe, effective therapy that could potentially be first-line treatment. It's a great addition to the armamentarium because it has no steroid side effects and very little burning" of the type seen with TCIs. However, he cautions, crisaborole may have difficulty replacing low-cost, low potency steroids in payers' formularies.
"Another exciting new class of drugs is the JAK inhibitors. They've shown promise both topically applied, and in case reports of oral use in AD, and they are being further developed," he says. Topical tofacitinib has demonstrated positive phase 2 results, he adds, and oral baricitinib remains in phase 2.
Among targeted biologic drugs, Dr. Simpson says dupilumab showed efficacy and safety with 16 weeks' use — without concomitant topical steroids — in phase 3 results.2 In one study, the proportion of patients who achieved investigator global assessment (IGA) scores of clear or almost clear at 16 weeks were 38% and 37% for those who received dupilumab every two weeks and weekly, respectively, versus 10% for placebo (P<0.001 in both analyses). A second study showed similar results: 36% of patients who received the drug weekly or every other week met the primary endpoint, versus 8% who received placebo (P<0.001 in both analyses).
"This is a dramatic game-changer in dermatology because we've had no safe, approved drugs for moderate to severe AD. Dupilumab would represent the first FDA-approved medication (outside of oral corticosteroids) for these patients who have suffered for decades using systemic steroids or immunosuppressants that are not approved for the condition," he notes. The FDA plans to render a decision in March. "Looking at the safety and efficacy data, I would expect it to be approved."
Many studies involving younger patients and/or longer-term use of the drug are ongoing, he adds. "It's an exciting breakthrough for all of us who care for these suffering patients."
Meanwhile, "There are many other exciting biologics that target itch and other inflammatory mediators in development. It is a new era for atopic dermatitis," he says.
Disclosures: Dr. Simpson has been a consultant and clinical investigator for Pfizer (maker of crisaborole), Regeneron and Sanofi-Aventis, although he owns no stock and has received no speaking fees from these companies.
1. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.e4.