Korsuva oral (difelikefalin oral) / Cara Therap, Chong Kun Dang, Maruishi Pharma, Kissei - LARVOL DELTA

Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica (clinicaltrials.gov) - P2/3 | N=214 | Terminated | Sponsor: Cara Therapeutics, Inc. | N=440 ➔ 214 | Trial completion date: May 2026 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Apr 2024; In Part A of CR845-310601, oral difelikefalin did not demonstrate a meaningful clinical benefit at any dose compared to placebo. The drug was generally well tolerated with a safety profile similar to prior trials.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Dermatology • Pruritus

CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3 | N=105 | Terminated | Sponsor: Cara Therapeutics, Inc. | N=400 ➔ 105 | Trial completion date: Oct 2024 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2024 ➔ Feb 2024; Corporate decision to discontinue work in advanced chronic kidney disease

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3 | N=286 | Terminated | Sponsor: Cara Therapeutics, Inc. | Trial completion date: Oct 2024 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2024 ➔ Feb 2024; Corporate decision to discontinue work in advanced chronic kidney disease.

Metastases • Trial completion date • Trial primary completion date • Trial termination • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Cara Therapeutics Announces Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "The Company enrolled 214 patients and expects topline efficacy and safety results from KOURAGE 1 Part A in the third quarter of 2024. Part A is not powered for statistical significance. This readout will provide key information, specifically the dose and sample size to initiate the Phase 3 pivotal portion of the program - Part B of KOURAGE 1 and the second study KOURAGE 2. Final topline results from the first pivotal study are expected by the end of 2025 with the second pivotal study results in early 2026."

P2/3 data • Pruritus

KIND-1: Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis (clinicaltrials.gov) - P3 | N=287 | Terminated | Sponsor: Cara Therapeutics, Inc. | Trial completion date: Feb 2026 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Feb 2025 ➔ Feb 2024; In Part A of the study, oral difelikefalin as adjunct to topical corticosteroids (TCS) did not demonstrate meaningful clinical benefit compared to TCS alone.

Trial completion date • Trial primary completion date • Trial termination • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Cara Therapeutics, Inc.

Metastases • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Cara Therapeutics, Inc.

Metastases • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica (clinicaltrials.gov) - P2/3 | N=440 | Recruiting | Sponsor: Cara Therapeutics, Inc.

Trial completion date • Trial primary completion date • Dermatology • Pruritus

Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica (clinicaltrials.gov) - P2/3 | N=440 | Recruiting | Sponsor: Cara Therapeutics, Inc.

New P2/3 trial • Dermatology • Pruritus

Oral difelikefalin reduces moderate-to-severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis. (PubMed, J Allergy Clin Immunol) - "DFK treatment reduced itch in subjects with moderate-to-severe AD-related pruritus, particularly those with an "itch-dominant AD phenotype", and impacted the expression of pruritus, Th2-associated, and skin barrier genes. DFK is a promising therapy for AD-related pruritus; further clinical studies are warranted."

Biomarker • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Metabolic Disorders • Pruritus • CYP1A2 • TRPV1

Efficacy and safety of oral difelikefalin in stage 3-5 chronic kidney disease patients with moderate-to-severe pruritus: a response analysis from a randomised, placebo-controlled, phase 2 trial (KSN 2023) - "Oral DFK 1.0 mg daily was identified as the optimal dose based on significant reduction in itch intensity and an acceptable safety profile. Further evaluation of DFK is warranted in"

Clinical • P2 data • Chronic Kidney Disease • Constipation • Dermatology • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Nephrology • Pruritus • Renal Disease

A Phase 2 Study of Oral Difelikefalin in Subjects With Chronic Kidney Disease and Moderate-to-Severe Pruritus. (PubMed, J Am Acad Dermatol) - "Oral difelikefalin significantly reduced itch intensity in stage 3‒5 CKD subjects with moderate-to-severe pruritus, supporting continued development for this condition."

Journal • P2 data • Cardiovascular • Chronic Kidney Disease • Constipation • Dermatology • Fatigue • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hypertension • Infectious Disease • Nephrology • Pruritus • Renal Disease

Rapid Reduction and Strict Complete Response in Itch With Oral Difelikefalin in Subjects With Notalgia Paresthetica and Moderate-to-Severe Pruritus (AAD 2023) - "In subjects with NP, 8 weeks of treatment with DFK led to rapid improvement in itch intensity. In addition, some patients achieved a strict complete response in itch as early as week 3. These findings support the role of kappa-opioid receptor activation to control neuropathic itch."

Clinical • Dermatology • Pruritus

Phase 2 Trial of Difelikefalin in Notalgia Paresthetica. (PubMed, N Engl J Med) - P2 | "Among patients with notalgia paresthetica, oral treatment with difelikefalin resulted in modestly greater reductions in itch intensity scores than placebo over a period of 8 weeks but was associated with adverse events. Larger and longer trials are needed to assess the efficacy and safety of difelikefalin treatment in this disorder. (Funded by Cara Therapeutics; KOMFORT ClinicalTrials.gov number, NCT04706975.)."

Journal • P2 data • Constipation • Dermatology • Gastroenterology • Gastrointestinal Disorder • Pain • Pruritus

Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus (clinicaltrials.gov) - P2 | N=14 | Terminated | Sponsor: Cara Therapeutics, Inc. | N=60 ➔ 14 | Recruiting ➔ Terminated; Slow enrollment due primarily to Covid-19

Enrollment change • Trial termination • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus and Not on Dialysis (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Cara Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus and Not on Dialysis (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Cara Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

KIND-1: Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Cara Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Cara Therapeutics Presents Late-Breaking Results of the KOMFORT Phase 2 Trial of Oral Difelikefalin for Pruritus in Notalgia Paresthetica at the 31st EADV Congress (GlobeNewswire) - "Cara Therapeutics, Inc...today announced results from the KOMFORT Phase 2 clinical trial of oral difelikefalin for the treatment of moderate-to-severe pruritus in notalgia paresthetica (NP). The data will be presented today by Mark Lebwohl, M.D...during a late-breaking news session at the 31st European Academy of Dermatology and Venereology (EADV) Congress."

A Phase 2 Study of Oral Difelikefalin for Moderate-to-Severe Pruritus in Subjects With Notalgia Paresthetica (KOMFORT) (EADV 2022) - No abstract available

Clinical • Late-breaking abstract • P2 data • Dermatology • Pruritus

Study to Evaluate the Efficacy and Safety of Oral Difelikefalin (CR845) for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica (KOMFORT) (clinicaltrials.gov) - P2 | N=126 | Completed | Sponsor: Cara Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Mar 2022 ➔ Jun 2022 | Trial primary completion date: Feb 2022 ➔ May 2022

Trial completion • Trial completion date • Trial primary completion date • Dermatology • Pruritus

Cara Therapeutics Announces Positive Topline Results from KOMFORT Phase 2 Trial of Oral Difelikefalin for the Treatment of Pruritus in Patients with Notalgia Paresthetica (GlobeNewswire) - "Cara Therapeutics, Inc...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)....'With no approved treatments available for notalgia paresthetica, the condition is challenging to manage and burdensome for patients,' said Mark Lebwohl, M.D...'These are encouraging results that underscore the potential for oral difelikefalin to be the first treatment option to address pruritus associated with notalgia paresthetica.'"

Announcement • Media quote

Oral Difelikefalin Reduces Atopic Dermatitis–Associated Pruritus (AAAAI 2022) - P2 | "Mice with topical MC903-induced AD were treated with DFK (0.5 mg/kg) intraperitoneally and itch was assessed early (30 minutes). A rapid, significant anti-pruritic effect of DFK was observed in an AD mouse model and in subjects with mild-to-moderate AD. These findings support the role of DFK as an anti-pruritic agent for patients with itch-predominant AD."

Addiction (Opioid and Alcohol) • Atopic Dermatitis • Dermatitis • Dermatology • Hypertension • Immunology • Inflammation • Pain • Pruritus • Xerostomia

Oral Difelikefalin Improves Itch and Quality of Life in Subjects With Itch-Dominant Atopic Dermatitis: Subgroup Analysis of a Randomized, Phase 2 Study (AAD 2022) - P2 | "Itch-dominant AD is associated with impaired QoL despite mild-to-moderate lesional severity, suggesting itch reduction should be a primary treatment goal in these patients. DFK showed clinically meaningful improvements in itch intensity, sleep, and QoL and may address the unmet need for a safe, effective antipruritic treatment in itch-dominant AD."

Clinical • HEOR • P2 data • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immunology • Pruritus • Sleep Disorder

KIND-1: Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis (clinicaltrials.gov) - P3 | N=280 | Not yet recruiting | Sponsor: Cara Therapeutics, Inc.

New P3 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus