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Difelikefalin

Phase 3

Uremic Pruritus | Small molecule | Nephrology |Fresenius Medical Care AG|Last Updated: May 1, 2026

Target and mechanism

Molecular targetOPRK1
Target classAgonist
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials1
Total Enrollment260

FDA Designations

No designations recorded

Clinical trial landscape

Difelikefalin · 3 trials · 4 indications

Phase 3 1Phase 2 1Phase 1 1
NCT05885737Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe PruritusUremic Pruritus
COMPLETED260 Analytics
PHASE3COMPLETED
Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus
Uremic PruritusUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period
From Baseline to Week 4

On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a numerical rating scale (NRS) scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The least square (LS) means of change from baseline to Week 4 in the weekly mean of the daily 24-hour WI-NRS score was estimated using the mixed model repeated measures (MMRM) method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects.

Incidence of adverse events (AEs)
Up to 18 weeks

To evaluate the safety of 0.5 μg/kg difelikefalin in HD adolescents (≥12 to \<18 years) with moderate-to-severe pruritus

Evaluation of the PK Profile of Difelikefalin - Cmax - Dose 1
1 week

Cmax = Maximum (peak) observed plasma concentration

Evaluation of the PK Profile of Difelikefalin - Tmax - Dose 1
1 week

Tmax = Time to reach maximum observed plasma concentration

Evaluation of the PK Profile of Difelikefalin - AUC0-t - Dose 1
1 week

AUC0-t = Area under the concentration-versus-time curve (AUC) from time zero to time "t"

AUCinf - Dose 1
1 week

AUCinf = AUC from time zero to infinity

AUCextrap(%) - Dose 1
1 week

AUCextrap(%) = percentage of AUCinf based on extrapolation

t½ - Dose 1
1 week

t½ = elimination half-life

Clearance - Dose 1
1 week

Clearance = the volume of blood or plasma that can be freed of a specified constituent in a specified time by its excretion into the urine through the kidneys

Vz - Dose 1
1 week

Vz = volume of distribution

Evaluation of the PK Profile of Difelikefalin - Cmax - Dose 3
1 week

Cmax = Maximum (peak) observed plasma concentration

Evaluation of the PK Profile of Difelikefalin - Tmax - Dose 3
1 week

Tmax = Time to reach maximum observed plasma concentration

Evaluation of the PK Profile of Difelikefalin - AUC0-t - Dose 3
1 week

AUC0-t = Area under the concentration-versus-time curve (AUC) from time zero to time "t"

AUCinf - Dose 3
1 week

AUCinf = AUC from time zero to infinity

AUCextrap(%) - Dose 3
1 week

AUCextrap(%) = percentage of AUCinf based on extrapolation

t½ - Dose 3
1 week

t½ = elimination half-life

Secondary Endpoints

Percentage of Participants Achieving Greater Than or Equal to (>=) 3-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period
From Baseline, and at Weeks 4, 8, and 12
Percentage of Participants Achieving at Least 4-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period
From Baseline, and at Weeks 4, 8, and 12
Change From Baseline in the Weekly Mean of the 24-hour WI-NRS Score at Each Week of the DB Period
From Baseline to Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
12-weeks double-blind period - DifelikefalinEXPERIMENTAL -
12-weeks double-blind period - PlaceboPLACEBO_COMPARATOR -
14-weeks optional open-label period following the double-blind period - DifelikefalinEXPERIMENTAL -
Single armEXPERIMENTAL -
1-week, single arm, open label treatment phaseEXPERIMENTAL -

Interventions

NameTypeDescription
Difelikefalin InjectionDRUGParticipants receive Difelikefalin three times a week (0.5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.
Placebo InjectionDRUGParticipants receive Placebo three times a week (0.5 micrograms/kg dry body weight). Placebo is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.
DifelikefalinDRUGThe study includes a screening period of up to 4 weeks (including a 7-day run-in period during the week prior to enrolment), a study treatment period of 12 weeks, and a safety follow-up visit at 7 (up to 10) days after EoT. Total study duration for a single participant is up to 17 to 18 weeks.
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Eligibility Criteria

Age Range18 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites35

Inclusion Criteria: * Subjects with chronic kidney disease (CKD) on HD 3 times weekly for ≥12 weeks prior to the informed consent procedure (including the date of informed consent) who can continue HD without changing its frequency or method. * If female, is not pregnant, or nursing. * If female: ...

Countries:ChinaGreeceIsraelSaudi ArabiaSpainUnited Arab EmiratesUnited Kingdom
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Frequently asked questions about Difelikefalin

What is Difelikefalin used for?

Difelikefalin is an investigational small molecule being developed for pruritus, including uremic pruritus in patients with end stage renal disease on hemodialysis. It is also being studied in adolescents with moderate-to-severe pruritus associated with chronic kidney disease.

Who makes Difelikefalin?

Difelikefalin is being developed by Fresenius Medical Care AG, a company listed on the New York Stock Exchange under the ticker symbol FMS.

What phase is Difelikefalin in?

Difelikefalin is in clinical development. It has completed a Phase 3 study in Chinese adults on hemodialysis with moderate-to-severe pruritus, completed a Phase 1 pharmacokinetic study, and is currently recruiting for a Phase 2 study in adolescents.

What clinical trials is Difelikefalin in?

Difelikefalin has three clinical trials. NCT05885737 is a completed Phase 3 study in Chinese adults with uremic pruritus. NCT05885763 is a completed Phase 1 pharmacokinetic study in Chinese adults on hemodialysis. NCT06593392 is a recruiting Phase 2 study in adolescents with pruritus.

Is Difelikefalin FDA approved?

Difelikefalin is not FDA approved. It is an investigational drug currently in clinical development, with trials ranging from Phase 1 to Phase 3, and has not received marketing approval.

What is the mechanism of action of Difelikefalin?

Difelikefalin is a small molecule therapeutic. Its specific molecular target has not been disclosed in the available clinical trial information.