Dapiclermin

Summary

Dapiclermin (also called repifermin, KGF‑2 or FGF‑10) is a recombinant human keratinocyte growth factor‑2 being investigated for topical use in epithelial repair. It is designed to stimulate epithelial cell proliferation and migration to accelerate wound closure, with research focusing on chronic venous ulcers and experimental models of dry eye disease.

Mechanism of Action

KGF‑2 binds the FGFR2b receptor, which is predominantly expressed on epithelial cells. Activation of this receptor triggers downstream MAPK and PI3K pathways that promote cell proliferation, migration, and differentiation, leading to mucosal thickening and re‑epithelialisation. In ocular models, KGF‑2 also down‑regulates the HMGB1/TLR4 inflammatory cascade, reducing cytokine release and tissue damage.

What the Research Shows

A double‑blind, placebo‑controlled trial in 94 patients with chronic venous ulcers showed that topical dapiclermin applied for 12 weeks increased the proportion of wounds achieving at least 75 % closure, especially in ulcers ≤15 cm² and ≤18 months old. Phase‑1 pharmacokinetic studies in monkeys and healthy volunteers demonstrated dose‑proportional exposure, high tissue binding, reversible epithelial mucosal thickening, and low immunogenicity. Animal studies of dry‑eye disease reported improved tear production and reduced inflammatory markers via HMGB1/TLR4 inhibition. Reviews highlight its potential for scar‑reduced healing, while plant‑based production strategies remain preclinical.

Reported Benefits

Clinical data suggest dapiclermin can speed closure of chronic venous ulcers, with a higher rate of substantial wound reduction compared with placebo. Early safety assessments indicate good tolerability and limited systemic adverse effects. Pre‑clinical ocular work points to anti‑inflammatory benefits that may translate to dry‑eye therapy, and mechanistic studies support a role in reducing scarring during tissue repair.

Limitations of the Evidence

Evidence is limited to a single moderate‑size ulcer trial and early phase‑1 PK studies; long‑term outcomes, optimal dosing, and comparative efficacy versus other growth factors are not established. Benefits appear confined to smaller, newer ulcers, and no large, multicenter trials have confirmed efficacy. Transdermal delivery is challenged by low skin penetration, and human ocular data are lacking. Production costs and formulation stability remain unresolved.

Safety Considerations

In monkeys, repeated dosing caused reversible thickening of gastrointestinal mucosa without affecting non‑epithelial tissues, indicating epithelial‑specific activity. Human phase‑1 participants showed dose‑proportional pharmacokinetics, minimal immunogenicity, and no serious adverse events. The ulcer trial reported the treatment as well tolerated. Potential risks include excessive epithelial proliferation and mucosal changes, but clinical safety data are still preliminary.

How It Is Administered

Dapiclermin is investigated as a topical formulation applied directly to the wound surface, typically once daily. Pharmacokinetic investigations have also employed intravenous and subcutaneous routes in early‐phase studies, but these are not part of the current investigational protocol for wound healing.

Routes of Administration

Goals & Uses

• Promotion of re-epithelializationTissue RepairModerate
• Wound healing (venous leg ulcers)Tissue RepairModerate
• Oral mucositis prevention/treatmentSupportive Oncology CareLow

Contraindications

• Hypersensitivity to dapiclermin or excipientsAllergy / ImmunologicHigh
• Known malignancy at or near wound siteOncologicHigh

Adverse Effects

• Local application site reactionsDermatologicCommon
• Wound exudate changesDermatologicUncommon
• Immunogenicity / antibody formationImmunologicUncommon

Drug Interactions

• Heparin / heparin-containing wound productsLow

Population Constraints

• Patients with active or recent malignancyOncologicRelative
• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionInvestigationalNo EMA marketing authorization granted. Clinical trials conducted but no approval pursued.
• United StatesInvestigationalNever received FDA approval. Investigated under IND for venous leg ulcers; development discontinued.

Dapiclermin was investigated by Human Genome Sciences and later Shire. It did not receive FDA or EMA approval. Phase II/III trials for venous leg ulcers were conducted but did not demonstrate sufficient efficacy to support a marketing application.

Evidence & Sources

• Handheld mechanical nociceptive threshold testing in dairy cows - intra-individual variation, inter-observer agreement and variation over time
  Journal ArticleModerateRaundal PM, et al.2014-01-01T00:00:00.000000Z
• Research progress and strategies for the biosynthesis of keratinocyte growth factor-2 (KGF-2) in Arabidopsis thaliana
  Journal ArticleModerateSong C, et al.2025-01-01T00:00:00.000000Z
• Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor-2) to accelerate wound healing in venous ulcers
  Journal ArticleModerateRobson MC, et al.2001-01-01T00:00:00.000000Z
• Scarless wound healing: Current insights from the perspectives of TGF-β, KGF-1, and KGF-2
  Journal ArticleModerateXiaojie W, et al.2022-01-01T00:00:00.000000Z
• Pharmacologic and pharmacokinetic profile of repifermin (KGF-2) in monkeys and comparative pharmacokinetics in humans
  Journal ArticleModerateSung C, et al.2002-01-01T00:00:00.000000Z
• KGF-2 Alleviates Dry Eye Disease by Regulating the HMGB1/TLR4 Pathway
  Journal ArticleLowWang Y, et al.2025-01-01T00:00:00.000000Z

Frequently Asked Questions