Cara Therapeutics Announces Positive Topline Results From Phase 2 Trial of Oral Difelikefalin 

Cara Therapeutics, Inc. recently announced positive topline results from its Phase 2 proof-of-concept clinical trial (KOMFORT) evaluating oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica (NP), a nerve disorder characterized by chronic pruritus of the upper to middle back.

“We are pleased to have demonstrated clinical proof of concept for oral difelikefalin in the treatment of pruritus associated with notalgia paresthetica,” said Joana Goncalves, MD, Chief Medical Officer at Cara Therapeutics. “These topline results coupled with the results from our other programs support the broad development of oral difelikefalin across disease areas regardless of the underlying cause of pruritus. We look forward to completing our data analyses and discussing next steps with the US Food and Drug Administration.”

“With no approved treatments available for notalgia paresthetica, the condition is challenging to manage and burdensome for patients,” said Mark Lebwohl, MD, the lead investigator and Professor and Dean for Clinical Therapeutics and Chairman Emeritus of the Department of Dermatology at Icahn School of Medicine at Mount Sinai. “These are encouraging results that underscore the potential for oral difelikefalin to be the first treatment option to address pruritus associated with notalgia paresthetica.”

The Phase 2 multicenter, randomized, double-blind, placebo-controlled, 8-week study was designed to evaluate the efficacy and safety of oral difelikefalin for moderate-to-severe pruritus in approximately 120 patients with NP. Patients were randomized to oral difelikefalin 2 mg taken twice daily versus placebo for 8 weeks, followed by a 4-week active extension period.

The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour Worst Itch-Numeric Rating Scale (WI-NRS) score at Week 8. Other endpoints included the ≥4-point responder analysis, itch-related quality of life scores, and safety assessments.

Patients treated with oral difelikefalin achieved the primary endpoint (-4.0 difelikefalin vs. -2.4 placebo, p=0.001) with significant improvement observed as early as Week 1 and sustained through Week 8.

In addition, a statistically significantly greater proportion of patients treated with oral difelikefalin achieved a ≥4-point improvement in WI-NRS score at Week 8 vs. placebo (41% difelikefalin vs. 18% placebo, p=0.007).

Oral difelikefalin was generally well tolerated with a safety profile consistent with that seen in earlier clinical trials. The most common treatment-emergent adverse events reported in ≥5% of patients treated with oral difelikefalin and greater than placebo were: nausea, headache, dizziness, constipation and urine output increased.

Notalgia paresthetica is a common, although under-recognized, chronic, sensory neuropathy affecting the upper back. It is estimated that chronic pruritus affects up to 13% of the population in the US, and about 8% of these patients suffer from neuropathic itch, including NP. One of the hallmark features of NP is chronic pruritus, which can be significantly burdensome and undermines the affected patients’ quality of life and overall well-being. The exact etiology of NP still has not been fully elucidated; however, it is widely accepted that NP is a sensory neuropathy caused by alteration and damage to thoracic spinal nerves.

The management of NP is challenging and is often resistant to multiple therapies. There is currently no approved treatment for NP and conventional treatments for pruritus, such as antihistamines and topical steroids, are largely ineffective.

Cara Therapeutics is a commercial-stage biopharmaceutical company leading a new treatment paradigm to improve the lives of patients suffering from pruritus. The company’s novel KORSUVA (difelikefalin) injection is the first and only FDA-approved treatment for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. The company is developing an oral formulation of difelikefalin and has initiated Phase 3 programs for the treatment of pruritus in patients with non-dialysis dependent advanced chronic kidney disease and atopic dermatitis. The company has completed the placebo-controlled phase of a Phase 2 proof-of-concept trial of oral difelikefalin for the treatment of moderate-to-severe pruritus in patients with notalgia paresthetica. A Phase 2 proof-of-concept trial in primary biliary cholangitis patients with moderate-to-severe pruritus is ongoing. For more information, visit www.CaraTherapeutics.com.