Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

Difelikefalin (Korsuva, CR845): what the evidence says

Name: Difelikefalin (Korsuva, CR845)
Published: 2026-10-27

At a glance

What it is: a synthetic peptide kappa-opioid agonist designed to stay out of the brain. Given IV after dialysis; approved as Korsuva in Aug 2021. A generic was approved in Aug 2026. ^{R1, R2, R3} UNVERIFIED the "all-D tetrapeptide" structure (not in sources opened).

What the evidence says: Human in KALM-1 (378 patients), 51% vs 31% had a meaningful itch drop at 12 weeks. ^R3 A phase 2 trial was also positive. ^R4

Biggest risks: diarrhea, dizziness and vomiting; the label warns about dizziness, sleepiness, mental-status changes and falls. ^{R3, R5}

Rating


Human Human evidence	Strong: KALM-1 RCT (n = 378) ^R3
Animal Animal / lab evidence	Not reviewed
Regulatory	FDA-approved ^R1 · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page ^{R6, R7, R8} · not named by WADA ^R9
Established human dose	Yes, label dose (see Study details)

Evidence verdict: Itch in hemodialysis patients: Strong (phase 3 RCT plus phase 2)

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: a double-blind phase 3 trial plus phase 2 support. Itch is subjective but was measured on validated scales.

What is it?

Related pages: kyotorphin, dalargin.

Does it work?

Human KALM-1: ≥3-point itch drop 49.1% vs 27.9% (imputed). ^R3
Human Phase 2 supportive. ^R4

Is it safe?

Human More diarrhea, dizziness, vomiting than placebo. ^R3

Gray-market vials: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.

Is it legal?

US: FDA-approved, prescription; generic available. ^{R1, R2}
Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. ^{R6, R7, R8}
Sport: not named on WADA's 2026 Prohibited List. ^R9

Study details

These are amounts researchers used, not recommendations.

Study	People / model	Route	Amount used	Follow-up	Reported	Citation
KALM-1 2020	378 hemodialysis patients with itch	IV, 3×/week	Per study	12 weeks	49.1% vs 27.9% responders	PMID 31702883

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)

^R1 Drugs@FDA, Korsuva (difelikefalin), application NDA214916 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA214916
^R2 Drugs@FDA, difelikefalin acetate generic, approved Aug 31, 2026, application ANDA220919 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=ANDA220919
^R3 Fishbane S, et al. N Engl J Med. 2020. PMID 31702883
^R4 Fishbane S, et al. Kidney Int Rep. 2020. PMID 32405581
^R5 Korsuva prescribing information, label published Aug 26, 2025 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c7b81f2-0fd3-47cb-8b0f-185e07f19c87
^R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R8 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
^R9 WADA. The 2026 Prohibited List, full list checked; compound not named. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Difelikefalin (Korsuva, CR845). This is a prescription medicine. Use it only under the care of a licensed clinician; do not buy it from research-chemical or gray-market sellers. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).