Edratide

Summary

Edratide (also known as hCDR1, CEL‑2000, TV‑4710) is an investigational immunomodulatory peptide derived from the complementarity‑determining region 1 of an anti‑double‑stranded DNA antibody. It is being studied as a disease‑specific therapy for systemic lupus erythematosus (SLE), aiming to restore immune tolerance and reduce disease activity.

Mechanism of Action

Edratide is a tolerogenic peptide that modulates immune pathways rather than acting on a single receptor. In pre‑clinical and early clinical studies it down‑regulates pro‑inflammatory cytokine genes (IL‑1β, TNF‑α, IFN‑γ, IL‑10) and BLyS, while up‑regulating immunosuppressive TGF‑β, FoxP3 and the anti‑apoptotic protein Bcl‑xL. These changes reduce lymphocyte activation, lower caspase‑3/8‑mediated apoptosis, and promote regulatory T‑cell function, collectively re‑balancing the dysregulated immune response characteristic of SLE.

What the Research Shows

Animal studies in murine lupus models showed that hCDR1 treatment corrected abnormal gene expression, reduced apoptosis, and diminished renal immune‑complex deposition, leading to clinical improvement. Gene‑expression profiling demonstrated restoration of ~22% of dysregulated genes, including reduced OX40‑ligand expression. In a small open‑label trial of nine SLE patients, 26‑week hCDR1 therapy lowered SLEDAI‑2K and BILAG scores and modulated cytokine and apoptosis‑related transcripts. A larger phase‑II trial (n=340) evaluated weekly subcutaneous doses of 0.5, 1.0 and 2.5 mg; the peptide was safe, primary SLEDAI endpoints were not met, but the secondary BILAG responder endpoint was achieved at the 0.5 mg dose, with trends at higher doses. Reviews cite Edratide among emerging biologic‑type agents for SLE, but it remains investigational.

Reported Benefits

Pre‑clinical data provide consistent evidence that Edratide can normalize lupus‑associated gene signatures, reduce pathogenic cytokine production, and limit apoptosis, translating into disease amelioration in mouse models. Early human data indicate a favourable safety profile and suggest modest clinical benefit, particularly on BILAG responder rates at low dose, and reductions in disease activity scores in a small cohort. These findings support its potential as a disease‑specific immunomodulator for SLE.

Limitations of the Evidence

The phase‑II trial did not meet its primary SLEDAI endpoints, and efficacy signals were limited to a single secondary measure at the lowest dose. The human gene‑expression study involved only nine participants, limiting generalisability. No regulatory approval has been granted, and long‑term outcomes, optimal dosing, and comparative effectiveness versus existing therapies remain undefined. Further larger, adequately powered trials are needed.

Safety Considerations

Across the phase‑II study, Edratide was reported as safe and well tolerated, with no serious adverse events highlighted in the abstract. The peptide’s tolerogenic nature appears to avoid overt immunosuppression, and the safety profile was deemed favourable enough to justify continued investigation. However, detailed adverse‑event data are not provided in the abstracts, and long‑term safety remains to be established.

How It Is Administered

Edratide has been administered subcutaneously on a weekly schedule in clinical studies, with dose levels ranging from 0.5 mg to 2.5 mg per injection. Formulations used in trials were injectable peptide solutions suitable for subcutaneous delivery.

Routes of Administration

Goals & Uses

• Reduction of anti-dsDNA antibody titersImmunological Biomarker ModulationModerate
• Reduction of lupus nephritisOrgan ProtectionLow
• Reduction of SLE disease activityAutoimmune/InflammatoryModerate
• Induction of regulatory T cellsImmunomodulationModerate

Contraindications

• Active serious infectionsInfectiousModerate
• Hypersensitivity to edratide or any excipientsAllergyHigh

Adverse Effects

• Flu-like symptomsSystemic/ImmunologicalUncommon
• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck

Drug Interactions

• Immunosuppressants (e.g., mycophenolate mofetil, azathioprine)Moderate
• CorticosteroidsLow

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalClinical trials conducted in Europe; no EMA approval granted.
• United StatesInvestigationalEvaluated in clinical trials under IND; never received FDA approval. Development discontinued.

Edratide has not received regulatory approval in any major jurisdiction. It was evaluated in Phase II clinical trials for SLE primarily by Teva Pharmaceutical Industries. Development appears to have been discontinued following failure to meet primary clinical endpoints.

Evidence & Sources

• Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study
  Journal ArticleLowUrowitz MB, Isenberg DA, Wallace DJ2015-01-01T00:00:00.000000Z
• [New therapeutic targets]
  Journal ArticleLowCalvo Alén J2008-01-01T00:00:00.000000Z
• The role of apoptosis in the ameliorating effects of a CDR1-based peptide on lupus manifestations in a mouse model
  Journal ArticleLowSharabi A, et al.2007-01-01T00:00:00.000000Z
• Altered gene expression in mice with lupus treated with edratide, a peptide that ameliorates the disease manifestations
  Journal ArticleLowElmann A, et al.2007-01-01T00:00:00.000000Z
• Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression
  Journal ArticleLowSthoeger ZM, et al.2009-01-01T00:00:00.000000Z
• [Systemic lupus erythematosus: future therapeutic avenues]
  Journal ArticleLowAmoura Z, Haroche J, Piette JC2008-01-01T00:00:00.000000Z

Frequently Asked Questions