Innocoll, Inc. has filed an Investigational New Drug (IND) application for its CollaRx Gentamicin as a topical antibiotic treatment for diabetic foot ulcers that are clinically infected or at risk of infection. CollaRx Gentamicin is a biodegradable and fully resorbable Gentamicin-Collagen Sponge formulated and manufactured using Innocoll's proprietary CollaRx technology. Upon application to a wound, the product releases gentamicin, a broad-spectrum, concentration-dependent aminoglycoside antibiotic, for local action. This achieves a high concentration of drug at the target tissue, while maintaining low systemic levels well below the toxicity threshold.

CollaRx Gentamicin, as a surgical implant, is already approved and marketed in Europe and other non-US territories as an adjunct to systemic therapy for the treatment and prevention of post-surgical site acquired infection. Published clinical case studies and anecdotal reports from clinicians using the marketed product strongly suggest its effectiveness in the treatment and cure of infected chronic wounds, including diabetic foot ulcers.

According to the centers for disease control and prevention, the estimated incidence of diabetes in the US exceeds 1.5 million new cases annually, with an overall prevalence of 20.8 million people, or 7 per cent of the nation's population. By 2030, the International Diabetes Federation predicts that the Global prevalence of diabetes will almost double from 193 million people (estimated in 2003) to 366 million.

An estimated 15 per cent of patients with diabetes will develop a lower extremity ulcer during the course of their disease. According to a large prospective study, approximately 7 per cent of diabetic patients with foot ulcers will require an amputation. Diabetic foot is the most common cause of nontraumatic lower extremity amputations in the US and Europe, with an average of 82,000 amputations per year in the US costing an estimated $1.6 billion annually. The estimated cost of foot ulcer care in the US ranges from $4,595 per ulcer episode to more than $28,000, for the 2 years post diagnosis. The total annual cost of foot ulcer care in the US has been estimated to be as high as $5 billion.

Practically all ulcers are colonized with pathogenic bacteria, and a high proportion become clinically infected requiring treatment with antibiotics. Orally administered and injected antibiotics are often associated with systemic side effects, and widespread use leads to development of bacterial resistance. Furthermore, diabetic ulcers are often associated with vascular disease and restricted peripheral blood flow (ischemia), which may render systemically acting antibiotics less effective. Infection can also spread to the bone (osteomyelitis), which is less well vascularised than soft tissue.

Currently, there are no topically applied antibiotics marketed in the US that are specifically indicated for the treatment of infected diabetic foot ulcers. Innocoll met with FDA in November 2005 to plan the clinical program and discuss the preclinical requirements that would support repeat dosing of chronic wounds. Innocoll recently completed the 28-day repeat dose toxicity study in an abraded wound pig model requested by FDA, which identified no local or systemic toxicity, or other adverse effects. This study, together with the previous human experience and pharmacovigilance data accumulated over more than 15 years use as a surgical implant provides an extensive safety database to underpin the IND application.

Innocoll plans to study the treatment of diabetic foot infections of varying severities, as defined according to the clinical classification in the IDSA Guidelines, in a series of phase 2 trials. The lead indication is the treatment of mild infection where CollaRx Gentamicin will be compared to an orally administered antibiotic. In subsequent trials, Innocoll plans to investigate the product as an adjunct to systemic therapy for treating infections of higher severity and also as a method to prevent ulcers from becoming clinically infected. Innocoll gratefully acknowledges the assistance and guidance of Prof. Benjamin Lipsky, (University of Washington), Prof. David Armstrong (Rosalind Franklin University) and Dr Michael Edmonds (King's College Hospital), as advisors in preparing the clinical development plan and protocols.

Commenting on the filing, Dr Michael Myers, president and CEO of Innocoll Inc., said, "Diabetes has reached epidemic proportions and is continuing to grow at an alarming rate across the globe. Diabetic foot is one of the major complications of the disease and with probable infection leading to possible amputation, this a huge problem for sufferers and an overwhelming burden on worldwide healthcare systems. We understand from talking to physicians that our product can and has saved limbs. Since there are no other topical antibiotics on the market for infected diabetic foot ulcers, we view this as an important step forward in treating and potentially preventing the condition. We look forward with great enthusiasm to working with our esteemed clinical advisors in performing the necessary controlled clinical trials that we believe will prove the safety and efficacy of CollaRx Gentamicin for these indications."

CollaRx is Innocoll Technologies' lead technology platform for the site specific targeted delivery of a wide variety of medicines with particular emphasis on antibiotics and anaesthetics. The CollaRx technology also forms the basis of Innocoll Pharmaceuticals lead product, Gentamicin Surgical Implant, a biodegradable leave-behind implant indicated for the treatment and prevention of post-surgical acquired infection in both hard and soft tissues. This product has been approved in over 40 countries and is marketed under the following different trade names (collatamp G, Collatamp EG, Sulmycin Implant, Garamycin Schwamm, Duracol, Duracoll, Gentacol, Gentacoll, Garacol, Garacoll, and Cronocol) in Europe, Middle East, Africa and Asia.