Dipexium Pharmaceuticals, LLC today announced modifications made to the Locilex(TM) (pexiganan acetate cream 1%) formulation have resulted in favorable chemical and physical stability as noted in 18-month stability testing by its manufacturer. Stability Trend Analyses at 18 months suggest a Locilex(TM) shelf-life of at least 36 months at room temperature. In addition, successful testing of this commercial-scale batch of non-cGMP material, in the to-be-marketed commercial packaging, utilizes a highly-purified active pharmaceutical ingredient (API), pexiganan acetate, at levels markedly above the purity level in the original formulation used by the prior sponsor of the Locilex(TM) development program. As previously reported, the United States Patent and Trade Office issued a notice of allowance for a new formulation and method of use patent on this novel Locilex(TM) formulation in June 2013.
"Evidenced by the manufacturing challenges faced by the prior sponsor of Locilex(TM), formulating a topical peptide is a complex process. We are extremely pleased that our novel Locilex(TM) formulation has addressed these challenges, resulting in vastly improved physical stability of the product," stated Robert J. DeLuccia co-Managing Partner of Dipexium. Mr. DeLuccia continued, "The impurity profile noted in the API used to formulate Locilex is now well within what could be considered acceptable standards."
"With the successful completion of our Locilex(TM) manufacturing and formulation modifications and the FDA's issuance of a Special Protocol Assessment Agreement for our proposed placebo-controlled, pivotal Phase 3 trial (Protocol DPX-305) in Mild Infections of Diabetic Foot Ulcers, we are now well positioned to move forward along our clearly defined regulatory pathway for our planned pivotal Phase 3 clinical program," stated David P. Luci, co-Managing Partner of Dipexium.
Dipexium plans to submit a CMC (Chemistry, Manufacturing & Controls) update to FDA and initiate patient enrollment in pivotal Phase 3 Study DPX-305 in the fourth quarter of this year.
Phase 3 Study Design
Study DPX-305 will be a randomized, double-blind, multi-center, superiority, placebo-controlled Phase 3 Study of Pexiganan Acetate 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"). The DFI Treatment Guidelines were published in the June 15, 2012 edition of Clinical Infectious Disease and is available on our website at
www.dipexiumpharmaceuticals.com.
About Special Protocol Assessments
The SPA process is a procedure by which the FDA provides official evaluation and agreement 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 our case, the results of Study DPX-306, an identical Phase 3 study intended to be conducted simultaneously with Study DPX-305.
About Locilex(TM)
Locilex(TM) (pexiganan acetate cream 1%) is a broad spectrum, topical antimicrobial peptide which is chemically synthesized from the skin of the African clawed frog. Locilex(TM) has a novel, bactericidal mechanism of action uncommon among antibiotics currently marketed which generally inhibit pathogen growth. Locilex(TM) (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.
Locilex(TM) 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(TM) clinical database recently by conducting microbiology studies that highlight the sensitivity of resistant bacteria to Locilex(TM), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum Beta-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(TM) may provide an important therapeutic advance.
In clinical trials, no safety concerns have been reported in over 1,000 human subjects exposed to Locilex(TM). 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(TM) could become the first topical antibiotic approved for the treatment of diabetic foot infection of any severity (mild, moderate or severe DFI) and the first prescription drug approved for patients with mild DFI.
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