Korsuva IV (difelikefalin IV) / Maruishi Pharma, Chong Kun Dang, Kissei, CSL Behring - LARVOL DELTA

Extemporaneous Preparation and Effectiveness of Low-Dose Naltrexone for the Treatment of Uremic Pruritus: A Literature Review and Case Report. (PubMed, Pharmacy (Basel)) - "Low-dose naltrexone provided symptomatic improvement in individuals with severe uremic pruritus when difelikefalin was inaccessible. While limited to a single case, this report highlights the potential role of naltrexone and underscores the need for further research to establish its safety and efficacy."

Journal • Chronic Kidney Disease • Dermatology • Nephrology • Pain • Pruritus • Renal Disease

CKD-Associated Pruritus: A Cross-Sectional Study (KIDNEY WEEK 2025) - "Difelikefalin(DFK) was taken by 21% of patients under medication, who complained about severe pruritus and had complete response (Graph 4,5)...This analysis confirms that DFK can effectively relieve severe CKD-aP. Further studies are required in order to understand the pathophysiology of CKD-aP and determine optimal treatment."

Observational data • Chronic Kidney Disease • CNS Disorders • Dermatology • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Pruritus • Renal Disease • Sleep Disorder • Type 2 Diabetes Mellitus

Identification of biomarkers associated with SUMO modification in heart failure. (PubMed, Medicine (Baltimore)) - "Subsequently, the results of drug prediction showed that CR845 might target CYLD in HF. PSME4 and CYLD were identified as SUMOylation-related biomarkers in HF, offering novel mechanism insights into the pathological underpinnings of HF."

Biomarker • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatology • Liver Failure • Targeted Protein Degradation

An Open-label, Single-arm Study to Evaluate the Safety and Tolerability of Intravenous Difelikefalin in Adolescents Aged 12 to 17 Years on Haemodialysis with Moderate-to-Severe Pruritus (ChiCTR) - P2 | N=18 | Not yet recruiting | Sponsor: Children's Hospital,Zhejiang University School of Medicine; Children's Hospital,Zhejiang University School of Medicine

New P2 trial • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Real-world safety of difelikefalin for chronic kidney disease-associated pruritus: initial insights from a European managed access programme. (PubMed, Clin Kidney J) - "No new safety signals were detected in this MAP analysis over a 3-year period. The overall safety results were consistent with the known safety profile for difelikefalin patients with moderate-to-severe CKD-aP receiving HD."

Journal • Real-world evidence • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Difelikefalin for CKD-aP: real world evidence of efficacy and safety in Italian patients. (PubMed, Clin Kidney J) - "Except for the two early therapy breaks, no other side effects were reported. In haemodialysis patients affected by CKD-aP, DFK is an effective and safe treatment that might clearly improve this distressing and overlooked condition."

HEOR • Journal • Real-world evidence • Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Nephrology • Pruritus • Psychiatry • Renal Disease

Meta-Analysis of Randomized Controlled Trials on Gamma-Aminobutyric Acid Analogues and Opioid-Based Therapies for CKD-Associated Pruritus. (PubMed, Kidney Int Rep) - "Our results suggest that GABA analogues and opioid-based therapies, particularly difelikefalin, have significant potential in alleviating itch intensity and improving the quality of life of patients with CKD-aP. However, opioid-based therapies, especially those involving μ-receptor antagonists such as naltrexone and nalbuphine, are associated with a higher incidence of AEs or ADRs. Given the substantial heterogeneity observed in most of the results, interpretation should be approached with caution."

Journal • Retrospective data • Chronic Kidney Disease • CNS Disorders • Dermatology • Nephrology • Pruritus • Renal Disease • Sleep Disorder

Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus (clinicaltrials.gov) - P3 | N=260 | Completed | Sponsor: Vifor Fresenius Medical Care Renal Pharma | N=184 ➔ 260

Enrollment change • Dermatology • Pruritus • Renal Disease

Pruritus in Uremic Patients: Approaches to Alleviating a Common Symptom in Chronic Kidney Disease. (PubMed, Life (Basel)) - "Difelikefalin, a κ-opioid receptor agonist, represents a breakthrough in systemic treatment, demonstrating efficacy with a favorable safety profile. Another opioid-based therapy, nalfurafine, has shown notable symptom relief in multiple clinical studies, with a low risk of abuse. Sertraline, an antidepressant, offers another alternative, although its delayed onset remains a limitation...Further research, including comparative and long-term studies, is essential to refine treatment algorithms and improve patient outcomes. By integrating new pharmacologic and nonpharmacologic options, CKD-aP management is shifting toward a more tailored and effective approach that addresses the individual needs of each patient."

Journal • Review • Chronic Kidney Disease • Dermatology • Inflammation • Nephrology • Pruritus • Renal Disease

Variation in Management of CKD-Associated Pruritus: Results From a Multinational Survey of Kidney Units. (PubMed, Kidney Med) - "Gabapentinoids (gabapentin or pregabalin) were the most widely used first-line systemic agent (49 units [47%]), followed by antihistamines (27 [26%])...Significant inter-country disparities were noted: doxepin, evening primrose oil, sertraline, and topical γ-linolenic acid were more frequently used in Australia than in NZ, and the UK, whereas hydroxyzine was preferentially used in UK units (P < 0.05). Units with a kidney supportive care service were more likely to use gabapentinoids, 5-hydroxytryptamine3 receptor antagonists, hydroxyzine, and topical therapies, and less likely to use promethazine (P < 0.05). Difelikefalin was not widely available during the survey period, which may limit generalizability. There is considerable variation in the management of CKDaP. Unexplained clinical variation suggests a need for the development of evidence-based guidelines and additional high-quality studies to inform care."

Journal • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Anti-inflammatory and renoprotective effects of difelikefalin, a kappa opioid receptor agonist, in a rat model of renal ischemia-reperfusion-induced acute kidney injury. (PubMed, BMC Nephrol) - "These findings indicate that difelikefalin has anti-inflammatory and renoprotective effects in a rat acute kidney injury model, with varying anti-inflammatory efficacy among KOR agonists."

Journal • Preclinical • Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury

Cost-Effectiveness of Difelikefalin for the Treatment of Moderate-to-Severe Chronic Kidney Disease-Associated Pruritus (CKD-aP) in UK Adult Patients Receiving In-Centre Haemodialysis. (PubMed, J Clin Med) - "Improved patient outcomes were achieved at an incremental cost of £7814 per person. Overall, at a price of £31.90/vial, difelikefalin was estimated to be a cost-effective treatment for moderate-to-severe CKD-aP at a willingness-to-pay threshold of £30,000/QALY, with conclusions robust to sensitivity analysis."

HEOR • Journal • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease • Transplantation

The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: a systematic review and network meta-analysis. (PubMed, Clin Kidney J) - "For the secondary endpoint, all four doses of difelikefalin were associated with higher rates of adverse events compared with placebo, while other interventions showed rates comparable to those of placebo and did not present statistically significant differences. In summary, difelikefalin at doses of 0.25 µg/kg and 0.5 µg/kg, along with nalfurafine at 0.25 µg/kg and 0.5 µg/kg, can be considered recommended therapeutic options for UP treatment."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • Dermatology • Pruritus

Recurrence of CKD-associated pruritus after discontinuation of long-term difelikefalin: a national real-life study. (ERA 2025) - "Recurrence of CKD-associated pruritus affecting nearly half of patients within 3-months of discontinuation of DFK. Further studies are needed to determine the efficacy of intermittent use and the frequency of sustained remission according to patient characteristics. Figure 1: Event free survival:"

Clinical • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus

Long-term efficacy and impact on quality of life of difelikefalin treatment in haemodialysed patients with moderate-to-severe chronic kidney disease associated pruritus (ERA 2025) - "Pruritus in our population was significantly associated with poorer QoL and higher psychological distress even though a lower prevalence (9.7%). Although the dropout rate was high in our study, the use of DFK, when well-tolerated, was associated with a dramatic response in pruritus scores and QoL improvement at 3 months which persisted up to 52 weeks of treatment. Those preliminary results obtained on a small sample size should be confirmed in further studies."

Clinical • HEOR • Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Mood Disorders • Nephrology • Pruritus • Psychiatry • Renal Disease • Sleep Disorder

Projections of infection-related cost savings associated with treating CKD associated pruritus (CKD-aP) with difelikefalin in five European countries through the combination of clinical trial data and real-world evidence (ERA 2025) - "CKD-aP is associated with significant infective hospitalization complications which translate into substantial costs. When modelling these estimates with the clinical effectiveness data of difelikefalin trials, national cost savings projections strongly advocate for the treatment of CKD- aP."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Coronary Artery Disease • Dermatology • Heart Failure • Infectious Disease • Nephrology • Pruritus • Septic Shock

Subcutaneous Lignocaine for CKDaP in a Haemodialysis Patient – Time to revisit an old remedy (ERA 2025) - "In addition to skin emollients, treatments sequentially included pregabalin up to a daily dose of 75mg, Evening Primrose Oil oral capsules up to 2 daily, dialysis initiation with extended hours nocturnal HD to optimise clearance (>6hours, Kt/V >2), oral cetirizine 10mg daily, and topical compound ointment (menthol 5%, lignocaine 7%, and capsaicin 0.025%)... Thereafter, the patient developed an acute exacerbation of itch affecting her entire body, associated with severe sleep disturbance, ferocious scratching (Figure 1), and emotional distress, despite continuing her existing treatments of emollients, pregabalin, difelikefalin 1mcg/kg, and an empirical course of ivermectin (follow up of skin scraping for scabies were negative)... Case CKDaP is a challenging condition to manage and severe cases can be extremely distressing for patients. Lignocaine blocks sodium channels in neuronal cell membranes and is widely and safely administered by CSCI in palliative care..."

Clinical • Chronic Kidney Disease • CNS Disorders • Dermatology • Diabetic Nephropathy • Hematological Malignancies • Infectious Disease • Lymphoma • Nephrology • Oncology • Pain • Palliative care • Pruritus • Renal Disease • Sleep Disorder • T Cell Non-Hodgkin Lymphoma

The prevalence and disease burden of CKD associated pruritus in Danish dialysis patients and current treatment practices (ERA 2025) - "Gabapentinoids (gabapentin and pregabalin) were rated third choice by most, but nephrologist prescribed pregabalin more than residents as their first or second treatment choice ( P=0.03 X2-test). Difelikefalin was not chosen (90%) or rated as fourth choice by 4% of nephrologists in our survey... Roughly one out of five patients on chronic dialysis treatment suffers from CKD-aP. HRQoL is negatively affected by CKD-aP primarily manifested as sleep disturbance. Most physicians tend to overestimate CKD-aP prevalence and use dialysis and fatty cream as their preferred treatment."

Clinical • Chronic Kidney Disease • CNS Disorders • Dermatology • Nephrology • Pruritus • Sleep Disorder

PAn-european Registry Addressing Difelikefalin In Goal-oriented Medical treatment for chronic kidney disease-associated pruritus (PARADIGM): Study design and research goals (ERA 2025) - "The PARADIGM study will advance the clinical understanding of CKD-aP treatment and provide essential real-world data on the use of DFK in the management of this condition in HD patients. By evaluating treatment patterns, effectiveness, safety, and HCRU, the study will help optimize DFK's role in CKD-aP management. The findings will inform clinical practice guideline development, future clinical trials, regulatory decisions, and healthcare policy, ultimately improving patient outcomes and enhancing the quality of life for CKD- aP patients undergoing hemodialysis.Figures: Figure 1."

Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Fatigue • Nephrology • Pruritus • Psychiatry • Renal Disease • Sleep Disorder

Exploring the second line agent of choice in the management of Chronic Kidney Disease-associated Pruritus: A global cross-sectional study of clinician experience and preference (ERA 2025) - "90% confirmed either gabapentin or pregabalin as their first-line in treatment of CKD-aP in line with best practice and current evidence...Other second line options includes first-generation antihistamines 13% (n=4) and Difelikefalin (7%). 3% (n=1) of respondents reported to use either UV-B phototherapy, oral Sertraline or topical Capsaicin cream respectively... Gabapentinoids continue to be the mainstay of CKD-aP treatment. This study highlights marked heterogeny in preferred second line option in management of this debilitating condition. Further research is required to develop guidance in CKD-aP symptom management."

Clinical • Observational data • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Assessment of safety from a European difelikefalin managed access programme (ERA 2025) - "No new safety signals were detected in this interim analysis of MAP data collected over a 3-year period. The overall safety results were consistent with the known safety profile of difelikefalin. These results could influence therapeutic recommendations, as difelikefalin may provide a favourable treatment option for patients with moderate-to-severe CKD-aP receiving HD."

Clinical • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Clinical experience with difelikefalin: 3 years after launch in Germany (ERA 2025) - "Sponsored by CSL Vifor."

Clinical • Chronic Kidney Disease • Dermatology • Pruritus

A retrospective multi-centre audit on efficacy and safety outcomes of difelikefalin use (UKKW 2025) - "In our real-world data, there is a considerable proportion of patients who did not receive a baseline WI-NRS assessment, rendering the sample size too small to analyse and to provide adequate statistical power. Larger sample sizes, with more fully documented WI-NRS assessments are needed for future observational studies. Our audit reflects the need for more data on efficiency, quality of life outcomes, impact on sleep and other related issues associated with CKD-aP which could be captured by the development of a registry."

Retrospective data • Addiction (Opioid and Alcohol) • Chronic Kidney Disease • Dermatology • Inflammation • Nephrology • Pruritus • Renal Disease

Difelikefalin for the management of severe pruritus in a hospital-based haemodialysis population: a Quality Improvement Project (UKKW 2025) - "In May 2023, NICE recommended Difelikefalin for the treatment of moderate to severe pruritus in adults with chronic kidney disease having in-centre haemodialysis, in whom other interventions such as creams and emollients, antihistamines and gabapentin had failed. 37 of the 93 (39.78%) hospital-based haemodialysis patients surveyed described severe itch (greater than or equal 7 on the WI-NRS scale) and were offered difelikefalin therapy. A decision was made not to proceed with difelikefalin for 12 of the 37 patients (32.43%): 3 had been admitted to hospital with new, intercurrent illness; 6 had moved haemodialysis centre; 2 went on holiday, and 1 patient did not attend haemodialysis sessions 3 times per week as prescribed. 10 of those 37 patients (27.02%) no longer experienced severe itch at the time of intervention and they were also excluded from the study."

Clinical • Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Nephrology • Pain • Pruritus • Psychiatry • Renal Disease

Nanoliposome-sericin hydrogel microneedle patches effectively alleviate inflammation and scavenge ROS for the treatment of CKD-aP. (PubMed, Mater Today Bio) - "The system integrates liposome-encapsulated capsaicin, known for its anti-inflammatory and analgesic effects, with methacryloyl sericin (SerMA) hydrogel-loaded Difelikefalin, a drug that modulates neural transmission and immune responses...Moreover, neural signal analysis showed reduced pruritus-related transmission, emphasizing its potential as a non-invasive, effective treatment for CKD-aP. These findings highlight the Cap@Lip/Dife-MNs microneedle system as a promising therapeutic platform for CKD-aP, with strong potential for clinical application."

Journal • Chronic Kidney Disease • Dermatology • Inflammation • Nephrology • Pain • Pruritus • Renal Disease