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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.
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.
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."
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
Poster of this presentation from DFCon is here (PDF file)
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.
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.
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
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???
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 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.
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).