EA-230

Summary

EA-230 is an investigational synthetic tetrapeptide (AQGV) derived from the beta‑chain of human chorionic gonadotropin. It is being studied for its ability to modulate systemic inflammation and protect renal function, particularly in settings such as experimental endotoxemia and cardiac surgery requiring cardiopulmonary bypass.

Mechanism of Action

EA‑230 is a linear tetrapeptide that appears to dampen the innate immune response by reducing the release of pro‑inflammatory cytokines (e.g., IL‑6, IL‑8, MCP‑1) after an inflammatory trigger. The peptide’s origin from hCG, a hormone associated with immunotolerance in pregnancy, suggests it may engage pathways that promote immune quiescence and enhance glomerular filtration, although the precise molecular receptors or signaling cascades have not been defined in the published studies.

What the Research Shows

Phase I trials in healthy volunteers demonstrated a large volume of distribution, rapid clearance and a very short plasma half‑life (≈0.3–0.4 min) with no safety signals across single, multiple and continuous intravenous dosing up to 90 mg·kg⁻¹·h⁻¹. In a phase IIa endotoxemia model, continuous infusion of EA‑230 (15–90 mg·kg⁻¹·h⁻¹) was well tolerated and significantly attenuated LPS‑induced rises in IL‑6, IL‑8, IL‑1ra, MCP‑1, MIP‑1α/β, VCAM‑1, fever and symptom scores. A subsequent phase IIb cardiac‑surgery trial (180 patients) confirmed safety; the primary immunomodulatory endpoint (IL‑6 AUC) was not different from placebo, but exploratory analyses suggested modest improvements in measured glomerular filtration rate, lower fluid balance, and a shorter hospital stay. No serious adverse events were reported.

Reported Benefits

Across early‑phase studies EA‑230 has shown an excellent safety and tolerability profile, with no drug‑related adverse events reported. In the endotoxemia model it reduced multiple inflammatory mediators, fever and symptom scores, indicating potential immunomodulatory benefit. In cardiac‑surgery patients, exploratory data suggested improved renal filtration, reduced fluid overload and a shorter hospital stay, hinting at renal‑protective and hemodynamic advantages in high‑risk surgical settings.

Limitations of the Evidence

The primary immunomodulatory endpoint (IL‑6 AUC) was not met in the cardiac‑surgery trial, and the observed renal benefits did not reach conventional statistical significance for all measures. Study populations have been limited to healthy volunteers, experimentally induced endotoxemia, and elective on‑pump cardiac surgery, restricting generalisability. The peptide’s very short half‑life may necessitate continuous infusion, which could limit practical use. No regulatory approval has been granted, and larger, diverse trials are still needed.

Safety Considerations

All published human studies (phase I, IIa, IIb) reported EA‑230 to be well tolerated with no drug‑related serious adverse events, hypersensitivity reactions, or laboratory abnormalities. The compound is rapidly cleared (high clearance, short half‑life) and does not accumulate with repeated dosing. No dose‑limiting toxicities were identified up to the highest investigated infusion rate of 90 mg·kg⁻¹·h⁻¹. Nonetheless, safety beyond the studied populations remains uncharacterised.

How It Is Administered

EA‑230 is administered exclusively by intravenous infusion. Phase I studies used single bolus doses (1–30 mg·kg⁻¹), multiple thrice‑daily doses (10–30 mg·kg⁻¹), and continuous infusions (15–90 mg·kg⁻¹·h⁻¹ for 2 h). The cardiac‑surgery trial employed a continuous infusion at 90 mg·kg⁻¹·h⁻¹ from the start of cardiopulmonary bypass until its termination. Formulations are investigational and supplied for clinical trial use only.

Routes of Administration

Goals & Uses

• Reduction of pro-inflammatory cytokinesCytokine ModulationModerate
• Attenuation of sepsis-associated systemic inflammationAnti Inflammatory / ImmunomodulationModerate
• Organ protection in ischemia-reperfusion injuryOrgan ProtectionLow
• Acute kidney injury prevention/treatmentNephroprotectionModerate

Contraindications

• Known hypersensitivity to EA-230 or its componentsAllergyHigh

Adverse Effects

• HeadacheNeurologicUncommonPain in the head or upper neck
• HypotensionCardiovascularUnknownLow blood pressure
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Infusion site reactionsLocalUncommon

Drug Interactions

• VasopressorsLow
• ImmunosuppressantsModeratePotential interaction with immune pathways or infection risk

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalPhase II trials conducted in EU (Netherlands); no EMA approval.
• United StatesInvestigationalNo FDA approval; investigational status only.
• United KingdomUnknownNo known MHRA approval or specific UK trial registration identified.

Not approved by FDA, EMA, or any major regulatory body. Developed by Exponential Biotherapies / Inflammatix. Phase II clinical trials conducted in the Netherlands and internationally. No approved indications as of last available data.

Evidence & Sources

• Pharmacokinetics, safety and tolerability of the novel β-hCG derived immunomodulatory compound, EA-230
  Journal ArticleModeratevan Groenendael R, et al.2019-01-01T00:00:00.000000Z
• Immunomodulatory and Kidney-Protective Effects of the Human Chorionic Gonadotropin Derivate EA-230
  Journal ArticleModeratevan Groenendael R, et al.2018-01-01T00:00:00.000000Z
• The Safety, Tolerability, and Effects on the Systemic Inflammatory Response and Renal Function of the Human Chorionic Gonadotropin Hormone-Derivative EA-230 Following On-Pump Cardiac Surgery (The EASI Study): Protocol for a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
  Journal ArticleLowvan Groenendael R, et al.2019-01-01T00:00:00.000000Z
• Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
  Journal ArticleModeratevan Groenendael R, et al.2021-01-01T00:00:00.000000Z
• A randomized double-blind, placebo-controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA-230 during experimental human endotoxaemia
  Journal ArticleModeratevan Groenendael R, et al.2019-01-01T00:00:00.000000Z
• The Human Chorionic Gonadotropin Derivate EA-230 Modulates the Immune Response and Exerts Renal Protective Properties: Therapeutic Potential in Humans
  Journal ArticleModeratevan Groenendael R, et al.2019-01-01T00:00:00.000000Z

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