Treatment for Skin Disease Targeting Children Tested

Peyton Fleagle’s parents first noticed uncomfortable scales on his skin when he was a toddler. Scales eventually covered nearly all of Peyton’s body. Fleagle, now 12 years old, suffers from X-linked ichthyosis, a skin disease that commonly disfigures children. The illnesses, which are collectively referred to as congenital ichthyosis, are distinguished by body-wide patches of dry, scaly skin. Ichthyosis alters how the skin regenerates by accelerating the production of new skin cells or slowing down the shedding of old skin cells. The U.S. Food and Drug Administration has not yet approved any treatment for ichthyosis.

But this situation could change.

A promising new treatment—an ointment created by Timber Pharmaceuticals—is being tested at Yale. Retinoic acid receptors in the nucleus of skin cells are the target of the treatment. In order to reduce the retention of old cells and the hyperactivity of skin creation, the treatment normalizes the cycle of skin cells.

The results are promising for Peyton Fleagle, who is taking part in a phase three clinical trial for the novel therapy at Yale New Haven Hospital. As a participant in the ointment’s prior clinical trial, he saw dramatic results. “It was like magic,” said his mother Christina Fleagle, who lives in Agawam, Massachusetts. “His skin completely cleared up. All the scales were gone.”

“When I’m not itching, I just feel different. I feel better because I’m not constantly scratching,” Peyton said.

Christopher Bunick, associate professor of dermatology at Yale School of Medicine and principal investigator for clinical trials of the new treatment at Yale, said Peyton’s experience is not unique. “Several of my patients have seen transformative results, where their scale is entirely clear, the skin clear for the first time. It is remarkable,” Bunick said. “The studies show that when patients use the medicine as indicated, most of them show improvement. It is not a cure, however.”

Bunick is the co-author of three articles that present the findings of the clinical trials, one of which will be released soon. Additionally, last year, Bunick presented the trial’s findings at an American Academy of Dermatology gathering.

The research examined phase two clinical trials (there are three phases of trials prior to potential FDA approval), which were concerned with the new drug’s patient-care efficacy, tolerability, and safety. The first study examined the safety and tolerability of two therapy concentration levels on 19 individuals and was published in the Journal of the American Academy of Dermatology (JAAD). The lower concentration was out to be more effective, although both amounts were confirmed to be safe.

The second study, also published in JAAD, examined the efficacy of the treatment using 33 patients and two key metrics: the Visual Index for Ichthyosis Severity (VIIS) scale system, created by Yale’s Department of Dermatology Chair Keith Choate, and the Investigator Global Assessment (IGA) score, a five-point scale of disease status for a variety of diseases. All patients who received the medication at a concentration of 0.05% experienced a 50% decrease in VIIS and two or more levels of IGA improvement.

The most recent trial, which was published in the journal Clinical and Experimental Dermatology, examined the efficacy of the novel drug in treating lamellar ichthyosis and X-linked recessive ichthyosis, two distinct kinds of congenital ichthyosis. The study’s findings showed that all skin disease types responded equally well to the treatment, with all patients achieving both the VIIS and IGA objectives.

The most recent instance of Yale’s significance in ichthyosis research is the university’s participation in the clinical trials—Yale is the only U.S. site involved in all three trials. Leonard Milstone, an emeritus dermatology professor at Yale, established a clinic, dedicated to the skin disease ichthyosis, more than 20 years ago. In 2017, Keith Choate established an ichthyosis registry at Yale and created the VIIS scale system along with Milstone and other scientists.

“The deep roots of ichthyosis research and clinical care at Yale, and now via the clinical trials, are on the verge of helping bring to ichthyosis patients the first FDA-approved medication,” Bunick said.

Many of those patients, Bunick said, experience emotional and psychosocial trauma in addition to the disease’s physical effects.

“From a young age patients must endure chronic fissured and scaly skin, often red and inflamed as well, making them targets for jokes or bullying at school,” Bunick said. “These patients are always ‘different’ due to their appearance. They have constant shedding of scales in their bedding, their clothing—parents endure that, too.”

The skin disease, Ichthyosis has caused the Fleagle family to experience a decade of concern, annoyance, Epsom salt baths, lotions, and oils. Other members of the family, such as Christina Fleagle’s father and uncle, also suffer from X-linked ichthyosis, although Peyton’s condition is by far the most severe. “His skin gets so dry, especially in the winter when the heater is running, that it feels like tissue paper and has these red lines,” Christina Fleagle said. “Peyton used to call it ‘cracking.'”

Bunick said ichthyosis also makes wound healing more complicated for patients, who are prone to infection and slow healing.

Bunick’s research will now concentrate on the Yale phase three clinical trial, which is currently recruiting volunteers. Mahin Dawood-Saffa and Nicole Olszewski were also praised by Bunick for their efforts in managing different phases of the trials with the Yale Center for Clinical Investigation.

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