Pexiganan for diabetic foot infections

NewsBot · Oct 4, 2007

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Press Release:
MacroChem Acquires Rights to Pexiganan, a Novel Topical Anti-Infective for Treatment of Diabetic Foot Infections, From Genaera

MacroChem Corporation (OTC Bulletin Board: MACM) today announced that it has exercised the option it acquired in July, 2007 to acquire exclusive worldwide license rights for drug uses of pexiganan, a novel, small peptide anti-infective for treatment of patients with mild diabetic foot infection (DFI), from Genaera Corporation.

“We believe this is a unique opportunity for MacroChem to broaden its product portfolio with a product that has already completed two Phase 3 clinical trials and that fits our strategic focus and complements our lead product candidate, EcoNail® for treatment of nail fungus,” stated Robert J. DeLuccia, President and CEO of MacroChem. “Both drugs would treat diseases of the foot predominantly treated by the same prescribing specialists, namely podiatrists. Both EcoNail and pexiganan are potentially of interest to a larger number of physician specialists and primary care physicians. MacroChem would ultimately be seeking a partner for marketing to those groups while retaining rights to market to selected physician specialists.”

In clinical trials previously conducted by Genaera, over 1000 human subjects were exposed to pexiganan without safety concerns, including 418 patients who received pexiganan in two Phase 3 clinical trials submitted in a New Drug Application to the U.S. Food and Drug Administration (FDA) in 1998. The primary clinical endpoint of one of the two Phase 3 trials was judged by the FDA to have been achieved. The other Phase 3 clinical trial, which did not meet its specified endpoint, provided strong supportive data indicative of the clinical benefit of pexiganan. At that time, difficulties with Chemistry Manufacturing & Controls (CMC) and an FDA request for one additional controlled trial precluded approval. MacroChem believes that since that time, significant improvements have been made in peptide manufacturing processes as well as in clinical trial design and execution. MacroChem plans to implement a program to address the previously identified CMC issues and resume formal dialogue with the FDA to determine the appropriate clinical development path.

“We are pleased to enter into an agreement with MacroChem Corporation for the therapeutic rights to pexiganan. This agreement reflects a first step in the execution of Genaera’s strategy to divest its non-core-assets, including Squalamine and LOMUCIN™. We believe pexiganan has significant potential to treat infected diabetic foot ulcers and that MacroChem is dedicated to the commercialization of this asset,” stated Dr. Henry Wolfe, Executive Vice President and Chief Scientific Officer of Genaera.

Mr. DeLuccia further noted, “We are pleased to have pexiganan in our hands since we believe that, if approved, it would be welcomed by physicians and patients for the treatment of diabetic foot infection. In recent years, there have been many advances in peptide manufacturing, a better understanding of the treatment of diabetic foot infection, improvements in clinical trial design and execution, and more clarity concerning regulatory requirements for topical anti-infectives, with the potential market being even more attractive than before.”

He added, “There continues to be a very large and growing incidence of diabetes and, as a result, a growing number of diabetic foot infections in the U.S. Diabetic foot ulcers in the approximately 20 million diabetics in the US alone are a major concern and burden to both patients and healthcare system. There is also a lack of effective topical anti-infectives to treat diabetic foot infection. Accordingly, we believe that pexiganan could fill an important unmet medical need for a topical anti-infective treatment and provide a significant commercial opportunity in an addressable market of millions of diabetic foot infections annually with a potential estimated half billion dollar market.”

Benjamin Lipsky, M.D., Professor of Medicine, University of Washington School of Medicine and Chairman of the Infectious Disease Society of America (IDSA) Guidelines Committee on Diabetic Foot Infection, commented, “I think there is a clear need for a topical antimicrobial compound for treatment of mild diabetic foot infections. Why expose the entire body to the potential toxic and microbial-altering effects of systemic therapy when the infection is limited to a superficial wound? With the growing problem of resistance of microorganisms to antibiotics, new types of antimicrobial agents and novel routes of treatment that allow lower doses of these agents would be welcomed. There are currently very few topical antimicrobial compounds available, none of which has been specifically proved to be effective for diabetic foot infections.”

Under the terms of the license agreement, MacroChem will pay Genaera an initial fee of $1 million through February 1, 2008. The deal terms also include payments of $7 million to Genaera upon the achievement of certain clinical and regulatory milestones through approval, sales-based milestones of up to $35 million, and 10% royalty payments on net sales. In addition, MacroChem will assume all clinical development, manufacturing and regulatory activities for pexiganan. MacroChem will require additional funding to fully develop the product.

About Pexiganan
Pexiganan is a 22-amino acid linear peptide. It is formulated as a cream and has a novel mechanism of action based on its ability to disrupt the integrity of bacterial cell membranes. It has antimicrobial activity against Gram positive (methycillin resistant staphylococcus aureus (MRSA)) and Gram negative organisms that commonly infect skin and soft tissue. It has a low potential for induction of resistance and no cross-resistance with existing therapeutic antibiotics as a consequence of its mechanism of action.

About Diabetes and Diabetic Foot Infection According to the U.S. Centers for Disease Control and Prevention (CDC), there are about 20.8 million people with diabetes in the U.S. (in 2005). Current estimates are that about 7% of all Americans have diabetes, and that prevalence is expected to increase each year. Among the complications caused by diabetes are foot disorders. It is estimated that up to about 25% of persons with diabetes will develop a foot ulcer in their lifetime of which about 60% get infected. Diabetic foot ulcers generally result from the consequences of peripheral neuropathy, with loss of protective sensations and foot deformities. The presence of peripheral vascular disease, increased biomechanical stress and acute trauma further increase the risk of foot ulcers. It usually takes several months for an ulcer to heal, and during this period there is a continual risk of foot infection. Infected foot ulcers can result in bone infection (osteomyelitis) or progressive gangrene, and are the major immediate cause of lower limb amputation. Diabetes is now the top cause of non-traumatic leg amputations in the developed world. Furthermore, foot ulcers are now the most frequent cause of diabetes-related hospitalizations. Thus, diabetic foot ulcers and infection are a major burden to both the patient and the healthcare system resulting in long-term disabilities and high demands on the healthcare system.
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Admin2 · Oct 4, 2007

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NewsBot · Mar 14, 2008

Press Release:
MacroChem Announces Presentation of Pexiganan Phase 3 Study Results for Topical Treatment of Diabetic Foot Infection
Combined data from two Phase 3 trials show clinical success rates statistically equivalent to oral antibiotic therapy

March 13 -- MacroChem Corporation (OTC Bulletin Board: MACM) announced today the presentation of a poster entitled "Topical versus Systemic Antimicrobial Therapy for Treating Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream." The poster will be presented at the Diabetic Foot Global Conference 2008 in Los Angeles on March 13 to 15 by Benjamin A. Lipsky, MD, FACP, FIDSA, Professor of Medicine, University of Washington and Director, Primary Care Clinic, VA Puget Sound Health Care System.

The poster presents results of two Phase 3 clinical studies, individually and combined, comparing the efficacy of an investigational topical antimicrobial peptide preparation, pexiganan acetate cream, against systemic therapy with an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers. The authors conclude, in part, that, "The rates of clinical cure or improvement (the primary outcome of the trial) for topical pexiganan and oral ofloxacin were statistically equivalent for the combined studies."

Dr. Lipsky commented that, "To my knowledge, these combined studies are the largest on treatment of diabetic foot infections ever conducted, the only ones that have compared these two routes of therapy, and the first to demonstrate the efficacy of a topical antimicrobial in treating diabetic foot infection in active-controlled trials. Furthermore, having an effective topical therapy available as an alternative to systemic treatment focuses attention on the wound and, in the case of pexiganan, uses a new antimicrobial, while avoiding adverse systemic effects and the promotion of antibiotic resistance."

"We are very pleased that these newly analyzed data are being presented for the first time at such a prestigious scientific meeting for professionals devoted to diabetic foot complications, including early recognition and treatment of diabetic foot infections," stated Robert J. DeLuccia, President and CEO of MacroChem. He continued, "We have initiated manufacturing and formulation programs to scale-up for an anticipated undertaking of one more Phase 3 trial, the design of which is to be confirmed upon meeting with the FDA later this year."

He further stated, "We believe that, if approved, pexiganan would be welcomed by physicians and patients. Diabetes is an enormous and growing problem worldwide and, as a result, there is an increasing number of diabetic foot infections. Diabetic foot ulcers are a major concern and burden to the approximately 20 million persons with diabetes in the US alone, as well as for the healthcare system. Additionally, there are currently no other topical anti-infectives that have been proven to be effective in treating diabetic foot infections. Accordingly, we believe that pexiganan could fill an important unmet medical need and provide a significant commercial opportunity for an addressable market of millions of diabetic foot infections annually, which translates to a potential estimated one-half billion dollar market in just the US."
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NewsBot · Mar 14, 2008

NewsBot said: ↑

MacroChem Announces Presentation of Pexiganan Phase 3 Study Results for Topical Treatment of Diabetic Foot Infection
Combined data from two Phase 3 trials show clinical success rates statistically equivalent to oral antibiotic therapy
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Poster of this presentation from DFCon is here (PDF file)

NewsBot · Nov 8, 2008

Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream.
Lipsky BA, Holroyd KJ, Zasloff M.
Clin Infect Dis. 2008 Nov 6. [Epub ahead of print]

Background; Topical antimicrobial therapy of infected diabetic foot ulcers can focus on the wound and avoid the adverse effects of systemic anti-infective agents. We compared the efficacy of outpatient treatment using an investigational topical antimicrobial peptide, pexiganan acetate cream, with the efficacy of systemic therapy using an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers.

Methods. In 2 consecutive, double-blind, controlled trials (study 303 and study 304), we randomized diabetic patients with a mildly infected diabetic foot ulcer to receive the active topical agent or active oral antibiotic, plus a respective inactive placebo. The primary outcome of interest was clinical cure or improvement of the infection. Secondary outcomes included eradication of wound pathogens and wound healing, which was documented by a semiquantitative scoring system.

Results; Overall, 835 patients were randomized; those in each treatment arm were similar with regard to demographic and clinical characteristics. Although study 303 failed to demonstrate equivalence, study 304 and the combined data for the 2 trials demonstrated equivalent results (within the 95% confidence interval) for topical pexiganan and oral ofloxacin in clinical improvement rates (85%-90%), overall microbiological eradication rates (42%-47%), and wound healing rates. The incidence of worsening cellulitis (2%-4%) and amputation (2%-3%) did not differ significantly between treatment arms. Bacterial resistance to ofloxacin emerged in some patients who received ofloxacin, but no significant resistance to pexiganan emerged among patients who received pexiganan.

Conclusions; Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.
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NewsBot · May 4, 2012

This clinical trial has just been registered:

Pexiganan Versus Placebo Control for the Treatment of Mild Infections of Diabetic Foot Ulcers

The purpose of this study is to establish the clinical superiority and the safety of topical pexiganan acetate cream 1% plus standard local wound care, as compared to placebo cream plus standard local wound care, in the treatment of mildly infected diabetic foot ulcers.
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Craig Payne · May 4, 2012

NewsBot said: ↑

This clinical trial has just been registered:

Pexiganan Versus Placebo Control for the Treatment of Mild Infections of Diabetic Foot Ulcers
Click to expand...

duh?
According to the Clinical Trial.org site:

Placebo Comparator: Vehicle control Drug: placebo cream
14 days of treatment
Experimental: Pexiganan acetate cream 1% Drug: pexiganan acetate cream 1%
14 days of treatment
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Why compare it to a placebo cream ... surely it should be compared to the gold standard of wound care? ... otherwise what is the point of the study and what information does it give us? How ethical is it to give a placebo cream to someone with a diabetic foot ulcer???

NewsBot · Jan 5, 2013

Press Release:
Dipexium Granted Special Protocol Assessment by the FDA for Phase 3 Registration Trial in Mildly Infected Diabetic Foot Ulcers With Locilex™

Dipexium Pharmaceuticals, LLC today announced that it has reached an agreement with the U.S. Food and Drug Administration ("FDA") on a Special Protocol Assessment ("SPA") 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. 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.

"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™ 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™ 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.

Study Design

Study DPX-305 will be a randomized, double-blind, multi-center, superiority, placebo-controlled Phase 3 Study of Pexiganan Cream 1% (Locilex™) 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 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 our case, the results of Study DPX-306, an identical Phase 3 study intended to be conducted simultaneously with Study DPX-305.

About Locilex™

Locilex™ (pexiganan acetate cream 1%) 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.

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™, including methicillin-resistant Staphylococcus aureus (MRSA), vancomyn-resistant enterococcus (VRE), extended-spectrum β-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 β-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™ 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).
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NewsBot · Jul 9, 2013

Press Release:
U.S. Patent includes Claims on Novel Formulation and Method of Treating Skin and Wound Infections

Dipexium Pharmaceuticals, LLC today announced it received a notice of allowance from the U.S. Patent and Trademark Office for a patent covering both a novel formulation of Locilex™ (pexiganan acetate cream 1%), an antibiotic peptide formulated as a topical cream, and the use of Locilex™ as a method of treating skin or wound infections. Dipexium currently is preparing for initiation of a Phase 3 trial of Locilex™ in mild infections of diabetic foot ulcers, which will be conducted under an existing Special Protocol Assessment agreement with the U.S. Food and Drug Administration with initiation of enrollment targeted for the second half of 2013. The patent to be issued from this allowed application carries an expected 20 year patent term to June 2032. Dipexium has also filed an application under the Patent Cooperation Treaty which could extend the patent protections of this new patent to up to 120 countries throughout the world.

"This new patent allowance is important to Dipexium for two reasons," stated David P. Luci, Co-Managing Partner of Dipexium, "First, it extends Locilex's™ patent life in the U.S. well beyond the currently issued patent and anticipated regulatory exclusivity periods. Second, we expect our PCT filing based on the allowed U.S application to eventually help us expand into major international markets such as Japan, China, Australia, Korea, Latin America and South America."

Robert DeLuccia, Co-Managing Partner of Dipexium, commented, "Currently, there are no FDA approved therapies for the treatment of mild infections of diabetic foot ulcers and there are no topical products approved or recommended for any severity of diabetic foot infections. We believe this soon to be issued formulation and method of use patent further validates the unique properties of Locilex™ relative to systemic treatments available to diabetics with infected foot ulcers as well as patients with other acute bacterial skin infections."

About Locilex™

Locilex™ (pexiganan acetate cream 1%) 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.

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™, including methicillin-resistant Staphylococcus aureus (MRSA), vancomyn-resistant enterococcus (VRE), extended-spectrum β-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 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™ does not absorb beneath the subdermal layer of the skin, systemic resistance to the drug cannot develop, unlike virtually all other currently available antibiotics.

Locilex™ has the potential to become the first topical antibiotic approved for the treatment of diabetic foot infection of any severity (mild, moderate or severe DFI).
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NewsBot · Sep 10, 2013

Press release
Dipexium Provides Locilex(TM) Manufacturing Update
- Novel Locilex(TM) Formulation Demonstrates Favorable Stability at 18 Month Testing - Initiation of SPA-Approved Placebo-Controlled, Pivotal Phase 3 Trial in Mild Infections of Diabetic Foot Ulcers Planned For Q4 2013

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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NewsBot · Jan 18, 2015

In Vitro Spectrum of Pexiganan Activity when Tested Against Pathogens from Diabetic Foot Infections and with Selected Resistance Mechanisms
R.K. Flamm, P.R. Rhomberg, K.M. Simpson, D.J. Farrell, H.S. Sader and Ronald N. Jones
Antimicrobial Agents and Chemotherapy; 12 January

Pexiganan, a 22-amino acid synthetic cationic peptide, is currently in Phase 3 clinical trials as a topical antimicrobial for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50/90 against all organisms tested from DFI was 16/32 μg/mL. Echerichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter spp. and Pseudomonas aeruginosa MIC values ranged from 8-16 μg/mL. Pexiganan MIC values among Staphylococcus aureus (MRSA and MSSA), β-hemolytic streptococci and E. faecium ranged from 8-32 μg/mL. Pexiganan activity was not adversely affected for Enterobacteriaceae or P. aeruginosa that produced β-lactamases or resistance mechanisms to other commonly used antimicrobials. Decreased susceptibility to vancomycin did not affect pexiganan activity against S. aureus nor against E. faecium. E. faecalis appears to be intrinsically less susceptible to pexiganan (MIC, 32-256 μg/mL). The “all organism” MIC90 of 32 μg/mL for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.
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NewsBot · May 22, 2015

Press Release;
Dipexium Announces Presentation at 7th International Symposium on the Diabetic Foot
Scientific Poster Presentation Highlights Design of Locilex® Phase 3 Pivotal Trials in Mild DFI

NEW YORK, May 21, 2015 /PRNewswire/ -- Dipexium Pharmaceuticals, Inc. (NASDAQ: DPRX), a late stage pharmaceutical company focused on the development and commercialization of Locilex® (pexiganan cream 0.8%), and clinical research collaborators, today announced a scientific poster presentation highlighting the innovative design of the Company's Phase 3 pivotal trials evaluating Locilex®, its novel, broad spectrum, topical antibiotic peptide, for the treatment of patients with mild infections of diabetic foot ulcers (Mild DFI), OneStep-1 and OneStep-2. The poster is being presented as a "late-breaker" at the 7th International Symposium on the Diabetic Foot (ISDF), the largest diabetic foot meeting in the world, May 20-23 in The Hague, The Netherlands.

The presentation, co-authored by Drs. Benjamin A. Lipsky (OneStep clinical trials' Chair), Michael Silverman (OneStep clinical trials' Medical Monitor), and Warren Joseph (OneStep clinical trials' Vice-Chair) and presented by Professor Lipsky, reported on the challenges associated with the design and implementation of a US FDA-mandated placebo-controlled trial of treatment of mild infections of diabetic foot ulcers. The authors highlighted the substantial consideration given to: protecting subject safety in a placebo-treated infection; selecting and characterizing an appropriate patient population; extensively training clinician investigators in standardized wound care techniques and trial procedures; quality monitoring oversight; and, rigorous definition of clinical assessments and endpoints.

The resulting OneStep trials' primary efficacy objective is to establish the clinical superiority of Locilex® versus placebo cream, with both groups receiving standard local wound care. Subjects with a mildly infected diabetic foot ulcer, as assessed by the standardized criteria of the 2012 Infectious Diseases Society of America Guideline for the Diagnosis and Treatment of Diabetic Foot Infections, and amenable to outpatient treatment, are randomized 1:1 to Locilex® or placebo cream. Standard local wound care consists of sharp debridement and pressure off-loading; investigators also take standardized wound photographs and digital measurements of wound area. Study medication is applied twice daily for 14 days, with subjects assessed for safety and efficacy during the treatment period, and at day 28. Investigators at 55 clinical trial sites in the U.S. have been trained and these sites are currently open for enrollment with more being added. The OneStep trials have been successfully enrolling and treating patients, and have surpassed the 25% enrollment milestone toward a total of 360 patients across both trials. For quality assurance, trial coordinators regularly review photographs and measurements taken at wound entry and follow-up. An independent expert Data Safety Monitoring Committee reviews cases of progression of infection and monitors for serious adverse events.

According to Dr. Lipsky, Emeritus Professor of Medicine, University of Washington, Visiting Professor, University of Geneva and University of Oxford, "This is the first large-scale, randomized, clinical trial to be conducted to assess the effect of adding antibiotic therapy to standard local wound care alone in the treatment of patients with mild diabetic foot infection. The OneStep clinical trial program is a groundbreaking study that has the potential to change the paradigm of treatment of this common and frequently limb-threatening infection. I am pleased to be able to present the trial design details at the ISDF and complement Dipexium for their effort in bringing these clinical trials to fruition."

Robert J. DeLuccia, Executive Chairman of Dipexium, stated "We believe the OneStep trial design is state of the art, and as evidenced by our Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA), a successful outcome will serve to fulfill the regulatory requirement to file a New Drug Application in the U.S. as a promising, first-in-class, broad-spectrum, non-systemic antibiotic treatment option for patients with mild DFI."

A copy of the ISDF poster presentation can be found in the "Investor Relations" section of Dipexium's website at www.dipexiumpharmaceuticals.com/locilex/key-publications.
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Pexiganan for diabetic foot infections

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Pexiganan for diabetic foot infections

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Pravibismane for diabetic foot infections

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Diabetic Foot Influencers on Twitter

Low Plasma Arginine among Patients with Diabetic Foot Ulcer

Epalrestat is effective in treating diabetic foot infection

Targeted exercises for the diabetic foot

Pranic Healing for Diabetic Foot Ulcer Management

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