Out of all patients diagnosed with diabetic foot ulcers (DFUs), approximately 58 percent suffer from a diabetic foot infection (DFI). DFI, a common complication of DFUs, if left untreated can carry the risk of amputation as well as severe sepsis and ostemyelitis. Chronic and ischemic ulcers carry the added risk of infections comprised of bacterial communities that display reduced susceptibility towards numerous antibiotics. While there are a number of antibiotics already on the market, such as Merck’s Invanz (ertapenem) and Pfizer’s Zyvox (linezolid) – both DFI indications – there’s a pressing demand for more therapies to help tackle hard-to-treat DFIs.
In an effort to face this challenge head on, Dipexium Pharmaceuticals and Innocoll had two topical antibacterial candidates, Locilex (pexiganan) and Cogenzia (gentamicin-collagen sponge), respectively in 2016. KOLs interviewed by GlobalData noted that the introduction of DFI topical antimicrobials would prove useful as adjunctive or standalone therapies for infections of ranging severity. As there are currently no topical antimicrobials approved for DFIs, such therapies would steal market share from the incumbent generic antibiotic market. Despite the potential of Locilex and Cogenzia, both agents flopped in phase III clinical trials in the 4th quarter of 2016, leaving the need for more effective antimicrobial DFI treatments unaddressed.
Dipexium Pharmaceuticals was developing Locilex, a broad-spectrum topical cream containing pexiganan acetate, for the treatment of mild infections of DFUs. Pexiganan acetate is a 22-amino acid synthetic analogue of the antimicrobial peptide magainin II, with a novel bactericidal mechanism of action. The general interest in the development of antimicrobial peptides as a treatment for infection has been pursued by drug developers, as it is believed that the likelihood of bacterial resistance developing to this class of drugs is lower than with conventional antibiotics. Dipexium conducted two pivotal phase III clinical trials, OneStep-1 and OneStep-2: randomized, double-blind, multicenter, placebo-controlled studies of Locilex applied twice daily for 14 days in patients with mild DFIs. In late October of 2016, Dipexium announced that Locilex did not meet the primary efficacy endpoint versus vehicle plus standard of care (SOC). Additionally, Locilex failed to meet the secondary endpoint of demonstrating a higher rate of bacterial eradication. As a result, Dipexium will consider pursuing alternative clinical indications for Locilex.
Likewise, Innocoll was developing Cogenzia, a gentamicin-collagen sponge that is applied to the open wound and releases gentamicin, a broad-spectrum aminoglycoside, potentially improving antibacterial efficacy at the wound site. Fully biodegradable and resorbable, Cogenzia was being developed as an adjunct to systemic antibiotic therapy. Innocoll has recently completed two pivotal Phase III clinical trials, COACT-1 and COACT-2, which were randomized, placebo-controlled, double-blind studies involving patients with moderate or severe DFIs who were being treated with Cogenzia on a daily basis as an adjunct to SOC, which included systemic antibiotic therapy. Patients were treated for a maximum of 28 days, and the primary endpoint was the percentage of patients clinically cured of infection 10 days after the discontinuation of all antibiotic therapy. In early November of 2016, Innocoll announced that Cogenzia did not meet its primary efficacy endpoint after 28 days versus either placebo plus SOC or SOC alone. As a result, Innocoll will now focus its assets on remaining pipeline candidates, which address postsurgical pain and adhesions.
Topical agents for DFIs have the potential to deliver high concentrations of antibiotics to the wound site without the risk of adverse effects associated with a systemic antibiotic. KOLs interviewed by GlobalData have expressed the continued need for drug developers to pursue topical agents to enter the DFI market. One advantage for any drug developer that enter this space is that even though a topical antibiotic may only be indicated for use as an adjunct to systemic antibiotic therapy, there is still the potential for it to be used as a standalone product, targeting a much larger patient population. With the recent failures of Locilex and Cogenzia, there are currently no topical antimicrobial treatments for DFI in phase III clinical trials across the US, European, or Japanese markets, leaving the opportunity open for a first to market therapy of this kind.
*This article first appeared on GlobalData Expert Insights on Dec. 22, 2016