Finafloxacin
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Finafloxacin - A highly differentiated, broad spectrum fluoroquinolone with a “best in class” safety profile targeting severe, hospital-treated bacterial infectionsMerLion Pharmaceuticals is seeking a commercialisation partner for finafloxacin, a novel fluoroquinolone, differentiated from its predecessors by an outstanding safety profile and powerful broad-spectrum antibacterial activity targeting difficult-to-kill bacteria at their sites of infection. Finafloxacin is most active in the acidified environments found at many infection sites (e.g. urine, abscesses, deep seated wounds, chronically infected tissues and stomach mucosa) and within the intracellular compartments of infected macrophages. The compound also shows impressive activity against persister and biofilm populations associated with chronic or recurring infections and demonstrates remarkable efficacy in a wide variety of in vivo infectious disease models. The compound has progressed successfully through early and mid-stage clinical development. Both oral and intravenous (iv.) formulations have shown excellent safety and good pharmacokinetics (supportive of once daily dosing). Phase IIa trials with the oral formulation showed impressive efficacy in combatting urinary tract infections (“UTI”) and for the eradication of Helicobacter pylori. Additional Phase II studies with the iv. formulation for complicated urinary tract infections (“cUTI”) and respiratory tract infections (“RTI”) are planned for 2011/2012. The following indications, involving a wide range of Gram positive and Gram negative pathogens, including anaerobes, are particularly suited for treatment with finafloxacin:
The broad applicability of finafloxacin offers opportunities for an extensive lifecycle build out. NDA filings in the cUTI and hCAP indications (both in Europe and the US) are anticipated as early as 2014 and 2016, respectively, with further clinical development warranted for ABSSSIs and IAIs. Additional opportunities for oral therapy include uncomplicated urinary tract infections (“uUTI”), extended RTI indications (including bacterial infections associated with cystic fibrosis) and H. pylori eradication. MerLion considers that further development of finafloxacin would ideally be carried out with a strategic partner qualified to undertake commercialisation of the drug.
Finafloxacin represents a compelling opportunity: 1. Ideal clinical and bactericidal features for wide therapeutic use - Broad Spectrum – broader than that of other fluoroquinolones, with proven in vivo activity against Gram positive, Gram negative, anaerobic and atypical pathogens including methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE) and potentially other multi-drug resistant pathogens. Finafloxacin also shows superior bactericidal activity against biofilms, slowly growing cultures and persister subpopulations which often cause the most serious and recurrent infections. - Potency against fluoroquinolone resistant strains enhanced under infection-relevant conditions – the antibacterial potency of finafloxacin is significantly enhanced in the acidic environments that prevail in many sites of infection (e.g. urine, lung secreta, abdominal fluid, abscesses, pelvic fluid and certain sub-cellular compartments). Under these low pH conditions the antibacterial activity of finafloxacin surpasses that of other FQs by up to 64-fold and thus, many FQ resistant strains are susceptible. This phenomenon, together with the high tissue levels of drug which can be achieved safely, is predictive of finafloxacin being an effective clinical treatment of infections caused by such FQ resistant strains. - Once daily (iv. and oral) dosing - supported by steady state PK profile and data from five clinical trials - IV/Oral switch capacity - oral and iv. formulations of finafloxacin provide important care step-down scenarios (i.e. from ICU to main ward and from inpatient to the community) 2. Externally validated by an industry-leader - In December 2010, MerLion entered into an exclusive license agreement with Alcon for the topical otic administration of finafloxacin for patients in North America - This agreement, which includes options to expand the compound’s use to include ophthalmic applications and to additional territories (up to and including worldwide rights), provides strong external validation of the quality and scarcity value of finafloxacin as a novel clinical candidate. |
