Diabetic foot ulcers (DFU) are a severe chronic diabetic complication that consists of deep tissue lesions, and at an advanced stage may be associated with neurological disorders and peripheral vascular disease in the lower limbs, often leading to amputation. Recent estimates suggest that DFUs affect 15% of all diabetes patients. DFUs often require extensive healing time and are associated with increased risk for infections that can result in severe and costly outcomes.
Studies have estimated that foot ulceration is one of the major sources of hospitalizations among patients with diabetes and precedes 84% of amputations of lower limbs in these patients. In addition, DFU patients have a low survival prognosis, with a 3-year cumulative mortality rate of 28% and rates among amputated patients approaching 50%.
The incidence of diabetic foot ulcers has increased due to the worldwide prevalence of diabetes mellitus and the successful prolonging of life expectancy for diabetic patients. A recent study estimates the total medical cost for treating diabetic foot diseases in the US alone ranges from $9 billion to more than $13 billion annually.
Current treatments for DFU include conventional wound management (e.g., debridement, moist dressings, and offloading areas of high pressure or friction) as well as more sophisticated treatments, such as bioengineered cellular technologies and hyperbaric oxygen therapy. However, an effective treatment for eradicating pathogens from infected diabetic foot ulcers remains a large, unsatisfied clinical need.
In 2017 Lakewood completed a Phase 1/2a clinical study using one of the first generation Bisphosphocins, Nu-3, for the treatment of infected diabetic foot ulcers. This trial was small (eight patients per cohort) but demonstrated that Nu-3 was safe to administer topically to an open ulcer using a basic saline solution formulation and 2% Nu-3 concentration. While the study was not intended to generate statistically significant efficacy data, it did yield an efficacy signal after one week of twice-daily treatment with the 2% Nu-3 concentration and showed no evidence of drug-related adverse side effects.
Patients treated with 2% Nu-3 for seven days had a 65.5% reduction in ulcer area versus a 29.9% reduction in the placebo arm, as measured 14 days after treatment began. In addition, 62.5% of patients treated with 2% Nu-3 saw a reduction in the microbiological load, versus 20% in the placebo. After Nu-3 is reformulated into a gel, an additional placebo-controlled, dose-escalating Phase 2a study to evaluate safety and efficacy is planned for Q2 2019. This study will extend treatment time from 7 days to 21 and will probe for further dose-escalation effects in 2, 5, and 10% formulations.