Aclerastide

Summary

Aclerastide (also known as DSC127, C21, or NorLeu3‑angiotensin (1‑7)) is an investigational peptide analogue of the renin‑angiotensin system being evaluated for the treatment of diabetic foot ulcers. Early pre‑clinical work suggested it could speed wound closure, and it entered Phase III trials as a topical agent, although later data indicated a lack of efficacy.

Mechanism of Action

Aclerastide is described as an analogue of angiotensin‑derived peptides that activates the AT2 receptor pathway. Reported actions include stimulation of progenitor cell proliferation, enhanced angiogenesis, collagen deposition and re‑epithelialisation, all of which can promote wound repair. Conversely, experimental work showed that treatment raised reactive oxygen species and activated matrix metalloproteinase‑9, a protease linked to chronic wound non‑healing, suggesting a dual mechanistic profile.

What the Research Shows

Pre‑clinical studies in diabetic mice reported that topical aclerastide accelerated vascularisation, collagen formation and overall wound closure, outperforming the reference product Regranex. These promising results led to Phase III clinical trials (NCT01830348, NCT01849965) recruiting patients with diabetic foot ulcers. However, a later animal study demonstrated that aclerastide treatment increased reactive oxygen species and active MMP‑9 levels, which are implicated in impaired healing and were proposed as reasons for the trial’s failure. To date, only these two peer‑reviewed reports provide data on aclerastide, and the clinical outcome remains negative.

Reported Benefits

Early animal work suggested that aclerastide could boost progenitor cell growth, stimulate new blood‑vessel formation, enhance collagen laying and speed re‑epithelialisation, leading to faster wound closure in diabetic models. The Phase III program was initiated based on these pre‑clinical advantages and the expectation of a higher proportion of fully healed ulcers compared with existing therapies.

Limitations of the Evidence

The most recent pre‑clinical evidence indicates that aclerastide raises ROS and active MMP‑9, enzymes known to hinder wound healing, which likely contributed to its failure in Phase III trials. Evidence is limited to animal studies and early‑stage clinical recruitment; no successful efficacy data have been published. Safety and optimal dosing remain undefined, and the peptide has not achieved regulatory approval.

Safety Considerations

No specific adverse‑event profile is reported in the available abstracts. However, the observed increase in reactive oxygen species and MMP‑9 activity raises concerns that aclerastide could exacerbate tissue degradation or impede healing in some patients. Overall safety has not been established, and further toxicological assessment would be required before clinical use.

How It Is Administered

Aclerastide has been investigated as a topical formulation applied directly to diabetic foot ulcers. The structured data also list a subcutaneous route, though no clinical data for that route are described in the abstracts. Formulation details and dosing regimens have not been disclosed in the published literature.

Routes of Administration

Goals & Uses

• Nerve regenerationNeurological RepairLow
• Fibrosis reductionTissue RemodelingLow
• Anti-inflammatory effectsInflammationLow
• Wound healing (diabetic foot ulcers)Tissue RepairModerate

Contraindications

• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Known hypersensitivity to aclerastide or excipientsAllergyHigh

Adverse Effects

• Local skin irritationDermatologicalUncommon
• HypotensionCardiovascularRareLow blood pressure

Drug Interactions

• ACE inhibitors / ARBsLow

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative

Regulatory Status

• European UnionInvestigationalClinical trials conducted in EU countries; no EMA approval.
• United StatesInvestigationalNo FDA approval; investigated under IND framework.

Not approved in any major jurisdiction. Investigated in Phase II clinical trials for diabetic foot ulcers. Developed by Vicore Pharma and previously by other entities.

Evidence & Sources

• NorLeu(3)-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers
  Journal ArticleModerateRodgers KE, et al.2015-01-01T00:00:00.000000Z
• Expression of active matrix metalloproteinase-9 as a likely contributor to the clinical failure of aclerastide in treatment of diabetic foot ulcers
  Journal ArticleLowNguyen TT, et al.2018-01-01T00:00:00.000000Z

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