For AD, 2017 Marks Ushering In of 'New Era'

Vivian Y. Shi, MD, an assistant professor at the University of Arizona and the director of the university Eczema and Skin Barrier Research Program

Vivian Y. Shi, MD

With 2 new therapies on the market, and a robust pipeline following behind, atopic dermatitis (AD) was a beacon of light for drug developers in 2017.

With 2018 around the corner, optimism remains high, but researchers say a number of hurdles remain, including patient access to the new therapies.

Dupilumab, a subcutaneous biologic sold under the brand name Dupixent, was approved by the US Food and Drug Administration (FDA) in March to treat adults with uncontrolled moderate to severe AD. Crisaborole, a first-of-its-kind topical PDE inhibitor sold as Eucrisa, hit the market this year following its December 2016 approval. Eucrisa is approved for the treatment of mild to moderate AD in patients 2 years of age and older.

Vivian Y. Shi, MD, an assistant professor at the University of Arizona and the director of the university’s Eczema and Skin Barrier Research Program, noted that the approval of dupilumab comes 2 decades after the first psoriasis biologic was approved.

“There are multiple reasons for the delayed approval of treatments for AD,” Shi told MD Magazine.

First, she noted that it simply takes a lot of time (and money) to develop these kinds of small molecule drugs and biologics.

“Secondly, [the delay is] because AD is a disease that predominantly affects the pediatric population, and many believe that it’s a disease that children will grow out of,” she said. “On the contrary, up to 5% of the adults worldwide are afflicted by AD, and children suffering from AD can have poor school performance and quality of life.”

Pediatric drug candidates are subject to more stringent monitoring protocols, making it all the more difficult and time-consuming for drug developers, Shi noted.

Shi and colleagues published a review of new and emerging AD therapies in a July article for the Journal of Dermatological Treatment.

If the current moment in AD research represents something of a new era, the biggest opportunity for advancement is in the treatment of severe AD, according to another recent review.

“Although mild and moderate forms of the disease can be well controlled by the use of emollients, topical corticosteroids, and topical calcineurin inhibitors, treatment of severe is still a huge challenge,” wrote the authors of an August review in Archivum Immunologiae et Therapiae Experimentalis.

They wrote that a better understanding of the pathomechanism of AD is creating the opportunity for more targeted, “tailor-made” biologics.

A dozen new AD-focused biologics are currently in drug company pipelines. Most are in phase 2 trials, though 2 compounds, tralokinumab and lebrikizumab, are in phase 3 trials. Each of those target the IL-13 pathway.

Those efforts are catalogued in a study in the September issue of The Journal of Allergy and Clinical Immunology, but the authors also note that even if new scientific advances are made, there are other questions that need to be resolved for the drugs to have a major impact.

“Although these emerging new therapies have the potential to revolutionize AD care, the extent of their effect on patient care will depend on their affordability and accessibility to patients with AD from a broad range of socioeconomic groups and with different insurance status,” wrote the study’s authors.

For instance, when dupilumab hit the market in March, it came with a list price of $37,000 per year. A 2-ounce tube of Eucrisa has a list price of nearly $600.

The September study also noted that while these new advances are generally focused on disease control, patients must continue to wait for a true cure for AD.

As research intensifies, Shi said another issue will be coordinating and tracking research in an efficient manner. At the moment, she said, there is no comprehensive database of AD trials, though an international task force has been established to do just that. The database will help track adverse effects, harmonize data collection on patients in trials, and make available long-term post-approval data on therapies like dupilumab.

“A comprehensive registry can reduce heterogeneity between registries of individual countries, allow pharma companies and researchers to directly compare data among individual trials, and facilitate data pooling between countries,” she said. “If made accessible to the general public, this consensus will allow AD patients to be more informed regarding current and future drug investigations, and become more proactive with participating in clinical trials.”