New formulation of FDA-approved drug shows encouraging results for treating a common itch condition

New York, NY (February 8, 2023) – 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 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).

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Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is ranked No. 14 nationwide in National Institutes of Health funding and in the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.