Iseganan

Summary

Iseganan (IB‑367) is a synthetic antimicrobial peptide derived from the protegrin family. It has been investigated in research settings for preventing oral mucositis in patients receiving chemotherapy or radiotherapy, and for reducing ventilator‑associated pneumonia (VAP) through oral decontamination. The compound never achieved regulatory approval and has been withdrawn from development.

Mechanism of Action

Iseganan is a cationic peptide that binds to microbial cell membranes, causing rapid permeabilization and death of a broad range of gram‑positive, gram‑negative bacteria, fungi and yeasts. By disrupting membrane integrity it also limits the development of resistance. In addition, protegrin‑derived peptides can neutralise lipopolysaccharide and dampen pro‑inflammatory cytokine release, providing modest immunomodulatory effects in the airway.

What the Research Shows

Early phase studies reported that topical oral iseganan reduced the incidence and severity of chemotherapy‑induced oral mucositis and associated pain, with good tolerability due to minimal systemic absorption. A large phase III trial, however, failed to confirm these benefits and the program was discontinued. In the intensive‑care arena, a randomized double‑blind trial of oral topical iseganan for VAP prevention showed a non‑significant trend toward lower VAP rates (16% vs 20%, p = 0.145) and no mortality advantage. A systematic review of oral decontamination found overall VAP reduction with antiseptics, but antibiotics other than iseganan drove the strongest effect, and no specific benefit for iseganan was demonstrated. Overall, the evidence consists of limited early positive signals followed by larger trials showing little or no efficacy.

Reported Benefits

Limited clinical data suggest that iseganan may modestly lower the risk of oral mucositis and associated pain when applied topically in the mouth, and it appears to be well tolerated with no systemic side effects. The peptide also shows broad‑spectrum antimicrobial activity in vitro, supporting its theoretical use for oral decontamination.

Limitations of the Evidence

Phase III data did not confirm efficacy for oral mucositis, and the VAP trial failed to reach statistical significance. Systematic reviews did not identify a clear benefit of iseganan over placebo or other agents. The program was withdrawn, and high‑quality, large‑scale studies are lacking, leaving the clinical value uncertain.

Safety Considerations

Across the reported trials, iseganan was well tolerated. No systemic absorption was detected after oral topical use, and adverse event rates were comparable to placebo. The VAP study reported no excess safety signals. Nonetheless, long‑term safety data are unavailable because development was halted.

How It Is Administered

Iseganan has been formulated for oral rinse or spray applied several times daily, and for nebulisation as an inhaled solution. In the VAP study the drug was given as an oral topical preparation six times per day while patients remained intubated. No injectable forms have been reported.

Routes of Administration

Goals & Uses

• Prevention of oral mucositisOncology Supportive CareLow
• Broad-spectrum antimicrobial activityAntimicrobial ResearchModerate
• Prevention of ventilator-associated pneumoniaInfectious DiseaseLow

Contraindications

• Hypersensitivity to iseganan or protegrin analoguesAllergyHigh

Adverse Effects

• Altered tasteSensoryUncommon
• Mucosal irritationLocal ReactionUncommon
• Oral discomfort/burningLocal ReactionCommon

Drug Interactions

No drug interactions recorded yet.

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant or lactating womenReproductiveRelative

Regulatory Status

• European UnionUnapprovedNever received EMA marketing authorization.
• United StatesUnapprovedFailed Phase III trials; no NDA filed or approved by FDA.
• United KingdomUnapprovedNot approved by MHRA.

Iseganan did not receive regulatory approval in any jurisdiction. Phase III trials for oral mucositis in cancer patients and for ventilator-associated pneumonia were discontinued after failure to meet primary endpoints. No approved indications exist.

Evidence & Sources

• Iseganan HCl: a novel antimicrobial agent
  Journal ArticleModerateGiles FJ, et al.2002-01-01T00:00:00.000000Z
• Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials
  Journal ArticleHighLi J, et al.2013-01-01T00:00:00.000000Z
• Antimicrobial therapy to prevent or treat oral mucositis
  Journal ArticleModerateDonnelly JP, et al.2003-01-01T00:00:00.000000Z
• Treatment of oral mucositis due to chemotherapy
  Journal ArticleModerateChaveli-López B, Bagán-Sebastián JV2016-01-01T00:00:00.000000Z
• A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia
  Journal ArticleModerateKollef M, et al.2006-01-01T00:00:00.000000Z
• The role of defensins in lung biology and therapy
  Journal ArticleModerateCole AM, Waring AJ2002-01-01T00:00:00.000000Z

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