Dipexium Pharmaceuticals, LLC today announced that it has reached an agreement with the U.S. Food and Drug Administration on a Special Protocol Assessment for an upcoming Phase 3 registration trial in mild infections of diabetic foot ulcers with Locilex (pexiganan acetate cream 1%), an antibiotic peptide formulated as a topical cream. 

 Locilex is a broad spectrum, topical antimicrobial peptide which is chemically synthesized from the skin of the African clawed frog. Locilex has a novel, bactericidal mechanism of action uncommon among antibiotics currently marketed which generally inhibit pathogen growth. Locilex (positively charged) forms an alpha helix and disrupts the lipid bilayer of the bacterial cell wall (negatively charged) thereby creating an opening into which intracellular fluid, extracellular fluid and water enter, effectively lysing the bacterial cell. 

The SPA agreement states that the proposed trial protocol design, clinical endpoints and planned analyses are acceptable to the FDA to support a regulatory submission. 

Study Design

Study DPX-305 will be a randomized, double-blind, multi-center, superiority, placebo-controlled Phase 3 Study of Pexiganan Cream 1% (Locilex(TM)) applied twice daily for 14 days to treat adult patients with mild infections of diabetic foot ulcers in the United States. Study DPX-305 will involve approximately 180 patients and the primary efficacy endpoint is resolution of infection in the medical judgment of each treating physician in accordance with the standardized guidance set forth in the 2012 Infectious Disease Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections (the "DFI Treatment Guidelines"), as published in the June 15, 2012 edition of Clinical Infectious Disease

The SPA process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a Biologics License Application ("BLA") or New Drug Application ("NDA"). Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 trial as well as, in othis case, the results of Study DPX-306, an identical Phase 3 study intended to be conducted simultaneously with Study DPX-305.

 "We are pleased with the agreement with the FDA which provides us with a clearly defined development and regulatory pathway for marketing approval of Locilex(TM) in mild infections of diabetic foot ulcers," stated Robert J. DeLuccia co-Managing Partner of Dipexium. "We believe pivotal Study DPX-305 will provide clinical justification to establish Locilex(TM) as the standard of care for the treatment of patients with mildly infected diabetic foot ulcers, a growing worldwide market currently estimated at approximately $1.5 billion," stated David P. Luci, co-Managing Partner of Dipexium.

Locilex has been used successfully in Phase 3 clinical studies demonstrating significant clinical benefit in patients with mild or moderate diabetic foot infections. Dipexium has supported the Locilex clinical database recently by conducting microbiology studies that highlight the sensitivity of resistant bacteria to Locilex(TM), including methicillin-resistant Staphylococcus aureus (MRSA), vancomyn-resistant enterococcus (VRE), extended-spectrum b-lactamase (ESBL) and multi-drug resistant (MDR) bacteria. Because of the increased prevalence throughout the world of multi-drug-resistant bacteria and XDR bacteria in all types of bacterial skin infections, Locilex may provide an important therapeutic advance.

In microbiology studies conducted recently, Locilex 's active ingredient demonstrated a high level of activity against multi-drug resistant (MDR) bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE) and extended-spectrum b-lactamase (ESBL) and other resistant pathogens.

Because of the increased prevalence throughout the world of multi-drug-resistant bacteria and XDR bacteria in all types of bacterial skin infections, Locilex may provide an important therapeutic advance.

In clinical trials, no safety concerns have been reported in over 1,000 human subjects exposed to Locilex. Importantly, no antimicrobial resistance, or cross resistance with other antibiotics, has been noted to date. Because Locilex(TM) does not absorb beneath the subdermal layer of the skin, systemic resistance to the drug cannot develop, unlike virtually all other currently available antibiotics.

If FDA approved, Locilex would become the first topical antibiotic approved for the treatment of diabetic foot infection of any severity (mild, moderate or severe DFI).  It is estimated that Mild Infections of Diabetic Foot Ulcers occur in approximately 1.5 million patients per year in the United States and constitute approximately one-half of the patients who first present with mild, moderate or severe Diabetic Foot Infection each year.