Advances in Treatment of Atopic Dermatitis, Part 2

The growing pipeline of therapies for atopic dermatitis has dermatologists optimistic about the future for individuals living with this disease.  

Drug Pipeline

table 2

Dermatologists are excited about the growing pipeline of drugs in development for eczema/AD. The Table highlights some therapies in phase 2 and phase 3 development. New and emerging therapies include PDE4 inhibitors, systemic therapeutics targeting AD immune pathways, and Janus kinase inhibitors.7,8

Biologics in development include nemolizumab, an IL-13 receptor agonist that inhibits the itch pathway, which is a common symptom in individuals with AD (See article on page 16). A 12-week, randomized, double-blind, placebo-controlled, phase 2 study showed a decrease of pruritus on the visual analog scale of 63% in individuals receiving 2 mg/kg every 4 weeks.9

“Targeted biologic therapies have the potential to modify the disease and relieve itch more effectively, without the severity of general immune suppression of other systemic medications,” said Dr Bruckner, who is also pediatric dermatology director for the Pediatric Dermatology Fellowship, Children’s Hospital Colorado.

A second topical PDE4 inhibitor, OPA-15406, has completed phase 2 studies in individuals aged 10 to 70 years with mild or moderate AD. In a randomized, double-blind, vehicle-controlled dose-finding study, Hanifin and colleagues compared 2 concentrations of OPA-1506 (0.3% and 1%) and vehicle. The ointment was applied twice daily to the AD-affected sites for 8 weeks. The primary endpoint was an IGA of 0 or 1, with a 2-grade reduction in AD severity at week 4. The endpoint was achieved in the 1% group (P=.0165 vs vehicle).10

“There is a balance of risk and reward,” noted Dr Bruckner. “Some of the new topicals are promising and may attract patients afraid of or intolerant of topical steroids. However, they will be very expensive. The systemic medications have the potential to clear moderate to severe AD but will also be expensive and patients will need to give them via injection, which may be intimidating for some, especially children.”

Future Outlook

Dermatologists are optimistic about the future landscape of eczema/AD treatments. For example, Dr Siegfried noted the attention from the FDA. In March 2015, the FDA’s Dermatologic and Ophthalmic, Drugs Advisory Committee, “unanimously decided on the importance of including children in early phase clinical trials so that pediatric labeling would be sooner rather than later for drugs in development,” she said.

Additionally, Dr Siegfried and colleagues developed a guidance document for new drug development in AD in children, which was submitted to the FDA and posted on the agency’s website. She said they are working on disseminating the information. 

References

1. D’Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. Drug Des Devel Ther. 2017;11:1473-1480.

2. Facts about eczema. National Eczema Association website. https://nationaleczema.org/wp-content/uploads/2016/08/Media-Kit-FINAL-08.11.16.pdf?2b800d. Accessed September 13, 2017.

3. Hon KL, Leung AK, Barankin B. Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol. 2013;14(5):389-399.

4. 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 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults: J Am Acad Dermatol. 2016;75(3):494-503.e6.

5. The first biologic approved to treat moderate to severe AD. The Dermatologist. 2017;25(4):42-44.

6. Simpson EL, Beiber T, Guttman-Yassky E, et al; SOLO 1 and SOLO Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.

7. Eichenfield LF, Friedlander SF, Simpson, EL, Irvine AD. Assessing the new and emerging treatments for atopic dermatitis. Semin Cutan Med Surg.  2016;35(5 suppl): S92-S96.

8. Renert-Yuval Y, Guttman-Yassky E. Systemic therapies in atopic dermatitis: the pipeline. Clin Dermatol. 2017;35(4):387-397.

9. Ruzicka T, Hanifin JM, Furue M, et al; XCIMA Study Group. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med.  2017;376(9):826-835.

10. Hanifin JM, Ellis CN, Frieden IJ, et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016;75(2):297-305.