Pipeline of Promise for Atopic Dermatitis

A steady stream of novel therapeutic agents is now navigating the atopic dermatitis (AD) pipeline.

Although Janus kinase (JAK) inhibitors have captured headlines as the FDA evaluates their efficacy and safety, there are more options on the horizon. A steady stream of novel therapeutic agents is now navigating the atopic dermatitis (AD) pipeline.

“In the past couple years,” says Peter Lio, MD, who spoke at the National Eczema Association’s Virtual Eczema Expo,1 “not only do we have some new treatments that have made a gigantic difference in patients’ lives already, but more importantly, that’s the tip of the iceberg.”2,3 He is a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine.

Oral JAK inhibitors

In mid-2021, the FDA extended Prescription Drug User Fee Act (PDUFA) dates for the following drugs.4-6 However, some oral JAK inhibitors hit a setback with the FDA’s September 1 decision to require warnings of serious health risks on JAK inhibitor tofacitinib (Xeljanz, Pfizer), which is used to treat rheumatoid arthritis among other conditions. The decision was expanded to include baricitinib (Olumiant, Eli Lilly and Company), and upadacitinib (Rinvoq, AbbVie) in the warning mandate.

"We eagerly await these new additions to the armamentarium for AD as we continue to have unmet needs and patients who have, quite literally, run out of options,” Lio says. “Although there are significant safety concerns with the JAK inhibitor class, I hope that we will be able to carefully review the specific safety data in the AD population so that we can better guide our patients in a shared decision-making process.”

Topical JAK inhibitors

Delgocitinib (LEO)—Phase 3 results in Japanese children show significantly greater reductions in modified Eczema Area and Severity Index scores versus vehicle.7 Stateside, delgocitinib has been FDA fast-tracked for chronic hand eczema.

Topical phosphodiesterase 4 (PDE4) inhibitor

  • Roflumilast (Arcutis)—Phase 3 results in patients age 6 years and up (NCT04773587, NCT04773600), and age 2 to 5 (NCT04845620) with mild-to-moderate AD are expected in late 2022.

Ayrl hydrocarbon receptor inhibitor

  • Tapinarof (Dermavant Sciences)—On September 9, Dermavant announced dosing of its first phase 3 patient with AD.8

Injectable biologics

  • Lebrikizumab (Eli Lilly and Company)—In mid-August, the FDA granted lebrikizumab fast-track designation in adults and adolescents with AD based on week 16 phase 3 results.9
  • Adtralza (tralokinumab, LEO Pharma)—FDA review continues after the agency requested additional data in April 2021.10
  • Nemolizumab (Galderma)—Phase 3 results in moderate-to-severe AD are expected in late 2022 (NCT03985943, NCT03989349) and late 2023 (NCT03989206).

References:

1. Lio P, Chovatiya R, Schoch J. Now hear this: the latest news in prescription treatments for eczema. National Eczema Association Virtual Eczema Expo; August 28, 2021.

2. Lio P. The latest news in Rx treatments for eczema. National Eczema Association Virtual Eczema Expo; August 28, 2021.

3. Lio P. Biologic treatments for eczema. National Eczema Association Virtual Eczema Expo; August 28, 2021.

4. Pfizer. Pfizer announces extension of review of New Drug Application of abrocitinib for the treatment of moderate to severe atopic dermatitis. Https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-extension-review-new-drug-application. April 7, 2021. Accessed September 10, 2021.

5. Eli Lilly. Lilly and Incyte provide update on supplemental New Drug Application for baricitinib for the treatment of moderate to severe atopic dermatitis. Https://investor.lilly.com/news-releases/news-release-details/lilly-and-incyte-provide-update-supplemental-new-drug. July 16, 2021. Accessed September 10, 2021.

6. AbbVie. AbbVie provides update regarding Rinvoq (upadacitinib) for the treatment of moderate to severe atopic dermatitis in the US. Https://news.abbvie.com/news/press-releases/abbvie-provides-update-regarding-rinvoq-upadacitinib-for-treatment-moderate-to-severe-atopic-dermatitis-in-us.htm?view_id=1310. July 16, 2021. Accessed September 10, 2021.

7. Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib ointment in pediatric patients with atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study [published online ahead of print, 2021 Jun 10]. J Am Acad Dermatol. 2021;S0190-9622(21)01116-6. doi:10.1016/j.jaad.2021.06.014 

8. Dermavant. Dermavant announces first patient dosed in ADORING, its pivotal phase 3 clinical program for tapinarof for the topical treatment of atopic dermatitis. https://www.dermavant.com/dermavant-announces-first-patient-dosed-in-adoring/. September 9, 2021. Accessed September 10, 2021.

9. Eli Lilly. Lilly's lebrikizumab significantly improved skin clearance and itch in people with moderate-to-severe atopic dermatitis in two phase 3 trials. Https://investor.lilly.com/news-releases/news-release-details/lillys-lebrikizumab-significantly-improved-skin-clearance-and. August 16, 2021. Accessed September 10, 2021.

10. LEO Pharma. Update on US FDA review of LEO Pharma’s Biologics License Application for tralokinumab for the treatment of adults with moderate-to-severe atopic dermatitis. Https://www.leo-pharma.us/Files/Billeder/leo-us/Press%20Release_FDA_Review_tralokinumab.pdf. April 29, 2021. Accessed September 10, 2021.

Disclosure:

Lio has been a speaker for Sanofi Genzyme, Regeneron Pharmaceuticals, Pfizer, Eli Lilly Company, LEO Pharma, Galderma, Incyte, and L'Oréal; an advisory board member for Almirall, ASLAN Pharmaceuticals, Dermavant Sciences, Sanofi Genzyme, Pfizer, LEO Pharmaceuticals, AbbVie, Eli Lilly and Company, Micreos, L'Oréal, Pierre Fabré, Johnson & Johnson, Level Ex, KP Away, Unilever, Menlo Therapeutics, Theraplex, IntraDerm, Exeltis, AOBiome, Realm Therapeutics, Altus Labs, Galderma, Verrica, Arbonne, Amyris, Bodewell, Yobee Care, Burt's Bees, MyOR Diagnostics, and Kimberly-Clark; a researcher for AOBiome, AbbVie, Regeneron Pharmaceuticals, and Sanofi Genzyme; a patent holder for Theraplex AIM (Splashe Brands, patent pending); and a stockholder in LearnSkin, Micreos, Yobee Care, Altus Labs, and KP Away.