Pipeline

Diabetic Foot Ulcer Infections (DFI)

Diabetic foot infections (DFIs) are the leading cause of diabetes-related hospitalizations and are among the primary reasons for lower limb amputation. While mild infections may be easily treated, moderate infections can threaten limb viability, and severe infections may become life-threatening. The estimated lifetime risk of developing a foot ulcer in individuals with diabetes mellitus ranges from 15% to 25%. The incidence and complications of DFIs have increased significantly, driven in part by the rising prevalence of multidrug-resistant (MDR) organisms. For example, the involvement of MRSA in DFIs in the US rose from 11.6% to 21.9% between 2003 and 2007. Gram-positive bacteria often predominate in acute DFIs, while Gram-negative and anaerobic bacteria are more common in persistent, chronic infections.

Research has shown that bacteria in many chronic wounds, including DFIs, frequently exist in biofilm communities. These biofilms are difficult to treat with systemic antimicrobial therapies and contribute to the development of antibiotic resistance. In a combined analysis of chronic wound studies, biofilm was present in nearly 80% of chronic wounds.

Standard-of-care treatment  is often ineffective for these patients. Even when infection is controlled, chronic diabetic foot ulcers may persist in a non-healing state, increasing the risk of re-infection and amputation. Ineffective management of DFIs can result in lower limb amputations, higher treatment costs, additional hospitalizations, and prolonged courses of systemic antibiotics, which further drive antibiotic resistance.

Our Solution

Microbion has completed two clinical studies evaluating the safety and therapeutic benefits of pravibismane in the treatment of diabetic foot ulcer infections. These early studies have demonstrated a favorable safety profile and compelling signals of efficacy.  We are currently planning a Phase 3 clinical study to further evaluate pravibismane’s potential to resolve infection and promote healing in diabetic foot ulcers.

Topically administered pravibismane, formulated as a hydrogel suspension, offers important advantages for the treatment of DFIs. These include dual broad-spectrum antimicrobial and anti-biofilm effects, as well as the ability to target antibiotic-resistant species. Additionally, pravibismane’s immunomodulatory activity appears to support ulcer healing, even in chronic, difficult-to-heal diabetic foot ulcers.

Pravibismane has been granted Qualified Infectious Disease Product (QIDP) designation and Fast Track status by the US FDA for adjunctive treatment of moderate and severe diabetic foot ulcer infections.

MBN-101-202 Diabetic Foot Infection Study

Microbion completed a Phase 2a clinical study to assess the safety and tolerability of a 3-times per week dosing, 12-week treatment regimen of topical pravibismane applied both at home and in out-patient wound care clinics. This randomized, controlled, multi-center, exploratory open-label study, enrolled 46 subjects (~2:1 randomization) with moderately infected, chronic diabetic foot ulcers in the outpatient wound care clinic setting. This study compared the administration of topical pravibismane in addition to standard of care (N=30) treatment for up to 12 weeks versus standard of care alone (N=16).  

The study’s main objective was to assess the safety and tolerability of topical pravibismane at higher concentrations than previous clinical trials and for a longer treatment duration of 12-weeks. The secondary objectives were to explore key signals of efficacy demonstrated in an earlier clinical study and assess the operational feasibility of at home administration of topical pravibismane.

The study met its primary objective of safety, demonstrating a favorable safety and tolerability profile over the 12-week treatment period and 4-week follow-up. 

• No adverse events attributable to topical pravibismane
• No treatment discontinuations due to drug-related intolerability
• PK data showed no evidence of systemic pravibismane exposure or accumulation
• Pravibismane had no observable effects on vital signs, clinical chemistry, hematology, ECG parameters, or other laboratory findings

While not powered for statistical efficacy, the study showed promising trends favoring topical pravibismane’s ability to heal chronic infected wounds, demonstrating complete wound closure in 52.6% of subjects using topical pravibismane as the sole pharmacologic intervention. 

In addition to the positive clinical safety results and numerical efficacy trends of this study, pravibismane’s potency against a broad-spectrum of drug-resistant bacterial isolates collected from subjects throughout the course of the study was re-confirmed. All infections treated in this study were comprised of multiple bacterial species. Importantly, all bacteria considered to be key pathogens in diabetic foot ulcers in this study, including those resistant to one or more antibiotics, were sensitive to pravibismane.