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New Medicines

Korsuva (US)Moderate-to-severe uraemic pruritus in haemodialysis patients

Information

Korsuva (US)
New molecular entity
Vifor Fresenius Medical Care Renal Pharma Ltd
Cara Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Approved (Licensed)
Aug 21Approved in US [19].
Mar 21Filed in EU via centralised procedure; a regulatory decision is expected Q2 22 [18].
Mar 21US FDA accept NDA for priority review, with a PDUFA of 23/8/21 [17].
Dec 20Cara has submitted a New Drug Application to the U.S. FDA for KORSUVA™ Injection (difelikefalin) for the treatment of moderate-to-severe pruritus in hemodialysis patients [16].
Nov 20The company remains on track to submit an NDA to the FDA Q4 2020.[15].
Apr 20Company still plan to file with the US FDA in H2 2020 and, working with partner Vifor Fresenius Medical Care Renal Pharma to submit for marketing Authorization Approval (MAA) to the EMA shortly after. [14]
Mar 19FDA and EMA filings are planned during 2020 [11].
Jun 18FDA assigns Breakthrough Therapy Designation to CR845 for treatment of uraemic pruritus, based on data from Part A of PII/III NCT02858726 study which reported 68% relative reduction in worst itching scores vs. placebo after 8 weeks [3].
May 18A joint venture of Vifor Pharma Group and Fresenius Medical Care (Vifor Fresenius Medical Care Renal Pharma Ltd [VFMCRP]) acquired an international license to commercialise Korsuva injection outside of the US, Japan and South Korea.[8]
Oct 17following a successful end of PII meeting with the FDA, Cara has established key elements of the pivotal PIII trial programme to support a New Drug Application (NDA) for CR845 for treatment of moderate-to-severe chronic kidney disease-associated pruritus in haemodialysis patients. The PIII trial will use a dose of 0.5 mg/kg, given IV, which met all efficacy endpoints in the multi-dose PII stage of the NCT02858726 study, and is also being studied in the open-label extension study (NCT03281538). Cara expects to initiate the PIII programme by the end of 2017 [6].

Category

A peptidergic, long-acting κ opioid receptor agonist
Uraemic pruritus develops in upwards of 60-70% of dialysis patients [1]. It is a severe itch associated with a 17% increase in mortality in haemodialysis patients [4].
Moderate-to-severe uraemic pruritus in haemodialysis patients
Intravenous

Further information

Yes

Trial or other data

Apr 20Positive topline data from KALM-2 PIII trial announced in hemodialysis pts with pruritus. Pts given difelikefalin had a reduction of at least 3 points in the 24-hour Worst Itching Intensity Numerical Rating Scale vs placebo (54% vs 42%, p=0.02. Difelikefalin was generally well-tolerated with the incidence of adverse events being similar across treatment and placebo groups. Common treatment-emergent AEs were diarrhea, falling, vomiting, nausea and dizziness.[14]
Nov 19PIII KALM-1 RCT (n=378) is published; it found that more patients given difelikefalin had a reduction of at least 3 points in the 24-hour Worst Itching Intensity Numerical Rating Scale vs placebo (49.1% vs 27.9%, p<0.001 [13].
May 19Cara Therapeutics announce positive results from PIII KALM-1 trial. Proportion of patients on 0.5mcg/kg dose achieving ≥3-point improvement from baseline in weekly mean of daily 24 hour Worst Itching Intensity Numeric Rating Scale score at week 12 was 51% vs. 28% for placebo (p=0.000019) [12].
Aug 18A second PIII trial of difelikefalin injection for treatment of moderate-to-severe CKD-aP in haemodialysis patients (KALM-2) starts (NCT03636269). The primary efficacy endpoint is the proportion of patients achieving at least a 3-point improvement from baseline with respect to the weekly mean of the daily 24-hour worst itching intensity NRS score at week 12. Primary outcome data collection is expected to be completed in Dec 19 [9,10].
May 18PIII KALM-1 study is recruiting and expects to complete collection of primary outcome data in Feb 19 [8].
Jan 18Pivotal PIII KALM-1 trial of difelikefalin injection for treatment of moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) in haemodialysis patients starts (NCT03422653). The primary efficacy endpoint is the proportion of patients achieving at least a 3-point improvement from baseline with respect to the weekly mean of the daily 24-hour worst itching intensity numeric rating scale (NRS) score at week 12. The 12-week trial, with a 52-week open label extension phase, is enrolling approximately 350 patients in the US. Results from the trial will be used to support a NDA [7].
Oct 17company reports positive top-line results from the PII phase of NCT02858726, with 174 patients treated. The trial met its primary endpoint with a 68% reduction in worst itching score vs. placebo (p<0.0019) at eight weeks [6].
Jun 17A 52-week PIII open label extension study (NCT03281538) is currently enrolling up to 240 hemodialysis patients with CKD-associated pruritus who have previously completed one of the company’s PII/III studies [5].
Jun 16PII/PIII trial (NCT02858726) initiated - phase A will assess the effect of three doses of CR845 vs. placebo, given by IV injection after dialysis sessions and the primary outcome will be intensity of itch after 8 weeks [2].

Evidence based evaluations

Korsuva (US)Acute postoperative pain

Information

Korsuva (US)
Licence extension / variation
Cara Therapeutics
Cara Therapeutics

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

A peptidergic, long-acting κ opioid receptor agonist which is designed to have reduced side-effects as compared with traditional µ opioid receptor agonists such as morphine
The company note that there are about 46 million inpatient and 53 million outpatient surgeries performed in the United States each year that require drugs for postoperative pain, and over half of these patients still experience inadequate pain relief [10]. In the UK in 2013/14, there were 4.7 million surgical admissions [11].
Acute postoperative pain
Intravenous