New Formulation of FDA-Approved Drug Shows Encouraging Results for Treating a Common Itch Condition
Positive Phase 2 clinical trial offers hope for patients with a common, yet underdiagnosed, nerve disorder known as notalgia paresthetica
Notalgia paresthetica—a nerve disorder characterized by a persistent itch in the upper back—is a common and underdiagnosed condition worldwide. To date, there are no FDA-approved treatments specifically targeting this disorder.
But a new study, published today in the New England Journal of Medicine, suggests that patients experiencing the moderate-to-severe itching associated with the disorder could potentially get relief with oral difelikefalin. The research was led by investigators at the Icahn School of Medicine at Mount Sinai.
Currently, difelikefalin—a selective kappa-opioid receptor agonist—is only FDA-approved as an injection for the treatment of moderate-to-severe itching associated with chronic kidney disease in adults undergoing hemodialysis.
“For those who experience chronic itch of any kind, relief can sometimes seem unattainable,” said principal investigator Brian S. Kim, MD, MTR, FAAD, the Sol and Clara Kest Professor of Dermatology, Vice Chair of Research, and Director of the Mark Lebwohl Center for Neuroinflammation and Sensation at Icahn Mount Sinai. “In this Phase 2 trial, treatment with difelikefalin resulted in a reduction in the intensity of itch in patients with notalgia paresthetica.”
In the double-blind, placebo-controlled trial, patients with moderate-to-severe itching from notalgia paresthetica were randomly assigned in a 1:1 ratio to receive oral difelikefalin 2 mg or a placebo twice daily for eight weeks. The primary outcome was the change over eight weeks in the weekly mean of the daily Worst Itch Numeric Rating Scale, in which 0 is “no itch” and 10 is “worst itch imaginable.” Secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.
Of 126 enrolled patients, 62 were assigned to receive difelikefalin and 63 to receive placebo. The baseline mean score on the Worst Itch Numeric Rating Scale was 7.6 (severe itch) in each group. The reduction from baseline in the worst itch score at week eight was 4.0 points in patients receiving difelikefalin versus 2.4 points for patients receiving placebo. Secondary outcomes were generally not supportive of the primary analysis. Headache, dizziness, constipation, and increased urine output occurred with difelikefalin.
Larger trials are needed to better assess the efficacy and safety of difelikefalin in notalgia paresthetica. If progress continues in a Phase 3 clinical trial, this medication would be the first FDA-approved drug specifically for people with notalgia paresthetica.
“The encouraging results achieved in this trial could reenergize the field and mark an important step toward improving symptoms of itch for patients with notalgia paresthetica,” said Dr. Kim, senior author of the paper, titled “Phase 2 Trial of Difelikefalin in Notalgia Paresthetica.”
Additional co-authors are Mark Lebwohl, MD (Icahn Mount Sinai); Robert Bissonnette; (Innovaderm Research), and Kristine Nograles, Catherine Munera; Nilam Shah; Alia Jebara; Josh Cirulli; Joana Goncalves; all with Cara Therapeutics, Inc., the funder of the trial and manufacturer of difelikefalin.
Dr. Kim and Dr. Lebwohl are paid consultants/advisors to Cara Therapeutics.
The trial is registered on ClinicalTrials.gov (NCT04706975).
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.