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Etavopivat Low dose

Phase 3

Sickle Cell Disease | Small molecule | Hematology |Novo Nordisk A/S|Last Updated: Aug 13, 2026

Target and mechanism

Molecular targetPKLR
Target classActivator
ModalitySmall molecule

Also known as Etavopivat Tablets Low dose, Etavopivat

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials6
Total Enrollment1,045

FDA Designations

No designations recorded

Clinical trial landscape

Etavopivat Low dose · 6 trials · 2 indications

Phase 3 2Phase 2 4
NCT06612268A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell DiseaseSickle Cell Disease
RECRUITING408 Analytics
NCT04624659A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)Sickle Cell Disease
ACTIVE NOT_RECRUITING450 Analytics
PHASE3RECRUITING
A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
Sickle Cell DiseaseUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)
Sickle Cell DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Baseline (week 0) to week 52

Measured as Count of events.

Hemoglobin response rate
24 Weeks

Hemoglobin response rate at Week 24 (increase of \> 1 g/dL \[\> 10 g/L\] from baseline) during the blinded treatment period

Annualized vaso-occlusive crisis
52 Weeks

Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review

Effect of etavopivat on cerebral blood flow (CBF)
24 weeks

Change in cerebral blood flow (CBF) assessments from baseline will be summarized with descriptive statistics by nominal study visit.

Effect of etavopivat on oxygen ejection fraction (OEF)
24 weeks

Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.

Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)
24 weeks

Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit.

Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD
Baseline and Week 12
Single-dose: maximum plasma concentration (Cmax)
During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from dosing (time 0) to time t ((AUC)0-t)
During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from zero to time infinity (AUC0-inf)
During the 24-week primary treatment period
Steady-state maximum plasma concentration (Cmax,ss)
During the 24-week primary treatment period
Steady-state area under the concentration time curve over the dosing interval (AUCtau,ss)
During the 24-week primary treatment period
Steady-state average plasma concentration (Cavg,ss)
During the 24-week primary treatment period
Steady-state minimum plasma concentration (Cmin,ss)
During the 24-week primary treatment period
Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs related to etavopivat
During the 24-week primary treatment period
Number of premature discontinuations
During the 24-week primary treatment period
Number of dose interruptions
During the 24-week primary treatment period
Number of dose reductions
During the 24-week primary treatment period
Cohorts A: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history
12 weeks

Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history

Cohorts B: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history
12 weeks

Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history

Cohort C: Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)
12 weeks

Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)

Secondary Endpoints

Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)
Baseline (week 0) to week 24
Time to onset of first adjudicated Vaso-occlusive crisis (VOC)
Baseline (week 0) to week 52
Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale
Baseline (week 0) to week 52
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
EtavopivatEXPERIMENTALParticipants will be randomised to receive oral dose of Etavopivat.
PlaceboPLACEBO_COMPARATORParticipants will be randomised to receive oral dose of placebo.
Double blind etavopivat Low DoseEXPERIMENTALDouble blind etavopivat Low Dose
Double blind etavopivat High DoseEXPERIMENTALDouble blind etavopivat High Dose
Double blind placeboEXPERIMENTALDouble blind placebo
Open label etavopivatEXPERIMENTALOpen label etavopivat
Etavopivat with HUEXPERIMENTALParticipants will receive Etavopivat 400 mg QD orally in combination with HU. The dose of HU (mg/kg) will be stable (no more than a 20% change in dosing except for weight-based changes) during the study, in the opinion of the Investigator.
Cohort 1: Etavopivat (12 to less than [<] 18 years)EXPERIMENTALParticipants aged 12 to less than 18 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in this age group.
Cohort 2: Etavopivat (6 to <12 years)EXPERIMENTALParticipants aged 6 to less than 12 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in this age group.
Cohort 3: Etavopivat (2 to <6 years)EXPERIMENTALParticipants aged 2 to less than 6 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in younger children.
Cohort 4: Etavopivat (6 months to <2 years)EXPERIMENTALParticipants aged 6 months to less than 2 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in infants.
Etavopivat 400 mg daily - SCD with transfusionsEXPERIMENTALPatients with sickle cell disease on chronic red blood cell transfusions
Etavopivat 400 mg daily - Thalassemia with transfusionsEXPERIMENTALPatients with thalassemia on chronic red blood cell transfusions
Etavopivat 400 mg daily - ThalassemiaEXPERIMENTALPatients with thalassemia not on chronic red blood cell transfusions

Interventions

NameTypeDescription
EtavopivatDRUGEtavopivat will be administered orally.
PlaceboDRUGPlacebo matching Etavopivat will be administered orally.
Etavopivat Tablets Low doseDRUG200 mg once daily
Etavopivat Tablets High doseDRUG400 mg once daily
Placebo TabletsDRUGPlacebo once daily
Etavopivat TabletsDRUGSelected dose once daily
HydroxyureaDRUGParticipants will receive a stable dose of HU.
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Eligibility Criteria

Age Range12 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites175

Inclusion Criteria: * Male or female. * Age 12 years or above at the time of signing the informed consent. * Confirmed diagnosis of sickle cell disease: Documentation of sickle cell disease (SCD) genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of lab...

Countries:United StatesAustraliaBelgiumBrazilCanadaColombiaFranceGhanaGreeceIndiaItalyKenyaLebanonNetherlandsNigeriaOmanSaudi ArabiaSpainTurkey (Türkiye)UgandaUnited KingdomEgyptGermany
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Recent Changes (Last 90 Days)

MEDIUMAug 14, 2026NCT06612268Completion: 2029-03-12 → 2029-08-12
MEDIUMAug 14, 2026NCT06612268Completion: 2029-03-12 → 2029-08-12
MEDIUMAug 14, 2026NCT06612268Completion: 2029-03-12 → 2029-08-12
MEDIUMAug 12, 2026NCT06198712lastUpdatePostDate: changed
MEDIUMAug 12, 2026NCT06198712lastUpdatePostDate: changed
LOWJun 18, 2026NCT06612268lastUpdatePostDate: changed
LOWJun 18, 2026NCT06612268lastUpdatePostDate: changed
LOWJun 18, 2026NCT06612268lastUpdatePostDate: changed
LOWJun 18, 2026NCT06612268lastUpdatePostDate: changed

Frequently asked questions about Etavopivat Low dose

What is Etavopivat used for?

Etavopivat is an investigational small molecule being studied for sickle cell disease, thalassemia, and liver diseases. It is also used in clinical trials involving healthy volunteers to assess safety, food effects, and pharmacokinetics. The drug is in Phase 1 clinical development and is not yet approved by regulatory authorities.

What does Etavopivat target?

Etavopivat targets and activates pyruvate kinase liver and red blood cell (PKLR), an enzyme involved in red blood cell metabolism. By activating PKLR, the drug aims to modify disease processes in sickle cell disease and thalassemia. This mechanism is under investigation in early-stage clinical trials.

Who makes Etavopivat?

Etavopivat is being developed by Novo Nordisk A/S, a pharmaceutical company listed on the New York Stock Exchange under the ticker symbol NVO. The company is conducting Phase 1 clinical trials to evaluate the drug's safety and pharmacological properties in various participant populations.

What phase is Etavopivat in?

Etavopivat is in Phase 1 clinical development. It is an investigational drug, meaning it has not received regulatory approval and is still being studied in early-stage trials. These trials focus on safety, tolerability, and how the drug behaves in the body, including studies in healthy volunteers and patients with liver disease.

What clinical trials is Etavopivat in?

Etavopivat has been studied in several Phase 1 trials. Completed trials include NCT06336018 in participants with liver disease, NCT06433661 on food effects in healthy participants, NCT06581627 in healthy Chinese participants, and NCT07023029 on heart rhythm effects. The drug has been evaluated in a total of six trials with 1,045 participants enrolled.

Is Etavopivat the same as Etavopivat Tablets Low dose?

Yes, Etavopivat is also known as Etavopivat Tablets Low dose and Etavopivat Low dose. These alternative names refer to the same drug substance, which is being developed by Novo Nordisk A/S for sickle cell disease, thalassemia, and liver diseases.