Drug Shows Promise Against “Unreachable Itch” Condition

Difelikefalin – a drug approved by the US Food and Drug Administration (FDA) for treating itching associated with chronic kidney disease (CKD) – has shown promise against the nerve disorder notalgia paresthetica (NP) in a clinical trial. The research is published in the New England Journal of Medicine.

No treatment for the “unreachable itch”

Ever have an itch that you just can’t seem to scratch? For some, the “unreachable itch” is actually a clinical condition. NP is a neuropathic syndrome where an itch and/or change in sensation occurs in the mid-upper back and can last for months to years. Currently, there are no FDA-approved drugs to treat the disorder and provide relief of the itching, which most often affects older women.

“For those who experience chronic itch of any kind, relief can sometimes seem unattainable,” says Dr. Brian S. Kim, a dermatology expert at the Icahn School of Medicine at Mount Sinai. Kim is also the principal investigator of a Phase II trial that has tested an already-approved FDA drug against NP.

The drug, difelikefalin, is a selective kappa-opioid receptor (KOR) agonist. These receptors were first associated with itching in the 20^th century, when animal studies demonstrated that KOR antagonists triggered scratching behaviors in mice. Difelikefalin is FDA-approved for the treatment of moderate-severe itching that occurs in patients with CKD and limits their quality of life. Whether this drug can be repurposed to treat other itching disorders required exploration.

Kim and colleagues recruited 126 NP patients to their double-blind, placebo-controlled trial, who were randomly assigned to receive either 2 mg of difelikefalin (n=62) or a placebo (n=63) twice per day for 8 weeks. One participant withdrew from the study and is therefore not included in the data analyses.

To understand whether the drug provides relief for NP patients, the study participants were required to complete a rating scale called the “Worst Itch Numeric Rating Scale” on a daily basis. The scale ranks levels of “itchiness” from 0 (no itch) to 10 (worst itch imaginable). The weekly average score for each participant was recorded for the duration of the trial, and then compared across the treatment and the placebo groups. Data on sleep and quality of life was also collected.

Encouraging results

Kim and colleagues found that the baseline average score for the entire trial cohort was 7.6 – a “severe” itch. “The change from baseline score at week 8 was −4.0 points in the difelikefalin group and −2.4 points in the placebo group,” the researcher say.

Patients receiving the drug reported side effects including headache, constipation, dizziness and increased urine output, a secondary outcome that the researchers say is generally not supportive of the primary analyses.

Larger and longer trials will be required to continue assessments into the safety and efficacy of the drug for treating NP patients. Depending on its performance in a Phase III clinical trial, it could become the first FDA-approved drug targeting NP.

“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,” Kim says.

Reference: Kim BS, Bissonnette R, Nograles K, et al. Phase 2 trial of Difelikefalin in Notalgia Paresthetica. N Engl J Med. 2023;388(6):511-517. doi: 10.1056/NEJMoa2210699.

This article is a rework of a press release issued by the University of Sydney. Material has been edited for length and content.