Pexiganan

Summary

Pexiganan is a synthetic 22-amino acid analogue of magainin 2, an antimicrobial peptide derived from African clawed frog (Xenopus laevis) skin. It was developed primarily for topical treatment of infected diabetic foot ulcers (DFUs). Despite showing efficacy in clinical trials, the FDA rejected its NDA in 1999 due to concerns about trial design. It was subsequently re-investigated and reached Phase III trials again under the brand name Locilex.

Mechanism of Action

Disrupts bacterial cell membranes by inserting into the lipid bilayer and forming ion channels or pores, leading to membrane depolarization, loss of osmotic integrity, and bacterial cell death. Broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria.

Routes of Administration

Goals & Uses

• Reduction of antibiotic resistance riskAntibiotic StewardshipLow
• Treatment of infected diabetic foot ulcersInfectious Disease / Wound CareModerate
• Broad-spectrum antibacterial activityAntimicrobialModerate
• Avoidance of systemic antibiotic exposureAntibiotic StewardshipModerate

Contraindications

• Application to deep or tunneling woundsWound CharacteristicsModerate
• Known hypersensitivity to pexiganan or excipientsAllergyHigh

Adverse Effects

• Contact dermatitisDermatologicalUncommon
• Systemic absorption-related effectsSystemicRare
• Application site painLocalCommon
• Application site erythemaLocalCommon

Drug Interactions

• Other topical antimicrobialsLow

Population Constraints

• Patients with severe or deep foot infectionsDisease SeverityRelative
• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionUnapprovedNo marketing authorization granted in the European Union.
• United StatesInvestigationalNDA rejected in 1999; second NDA received Complete Response Letter in 2016 requesting additional efficacy data. Not currently approved.
• United KingdomUnapprovedNot approved by MHRA.

FDA rejected original NDA in 1999 (Genaera Corporation) due to non-inferiority trial design concerns. Re-developed by Dipexium Pharmaceuticals as Locilex (pexiganan cream 0.8%); received Complete Response Letter from FDA in 2016, citing need for additional clinical data to demonstrate superiority or non-inferiority. Not currently approved in any jurisdiction.

Evidence & Sources

No sources recorded yet.