Cempra Pharmaceuticals today announced data presentations of its lead antibiotic candidate, CEM-102 (fusidic acid), at the Infectious Diseases Society of America, 47th Annual Meeting, Oct. 29 to Nov. 1, 2009, in Philadelphia.
Fusidic acid is a compound with an established record of treating staphylococcal infections, including methicillin-resistant S. aureus (MRSA), outside the U.S., a unique mechanism of action and low levels of bacterial resistance. CEM-102, a new oral formulation of fusidic acid and with a PK-PD-based dosing regimen, is being investigated for the treatment of acute bacterial skin structure infections in a Phase 2/3 clinical trial vs. linezolid. This adaptive-design trial is expected to transition into a Phase 3 pivotal trial in the first quarter of 2010.
Three posters to be presented at IDSA on October 30 (12:30 to 2 p.m. EDT) confirm CEM-102's potency against contemporary isolates of S. aureus, including MRSA, from the U.S. and Canada, with MIC90s in the 0.25 micrograms/ml range (Posters 202, 203, 261). Isolates resistant to other antibiotics were susceptible to CEM-102, indicating little cross resistance to CEM-102. Importantly, resistance to CEM-102 increased only slightly and remained low (less than 10% of isolates), in Canadian strains isolated between 2001 and 2008 despite fusidic acid being available in Canada since 1987 (Poster 202). Mutational frequency of two strains of MRSA following a single exposure to CEM-102 was shown to be low providing further evidence of the low likelihood for the development of bacterial resistance (Poster 203). The robustness of the results from these studies was confirmed by an analysis of bacterial susceptibility to CEM-102 using three different susceptibility testing methods (Poster 261). The prior studies employed broth microdilution. In this study, broth microdilution, disk diffusion and Etest methods showed highly correlated susceptibility results across multiple S. aureus strains.
An oral presentation, scheduled at 3:30 p.m. EDT, October 31, presents evidence, through a pharmacokinetic-pharmacodynamic model based on drug clearance data from 69 healthy subjects, that a loading dose of CEM-102 on the first day of treatment can generate significantly better antibacterial effects compared to regimens without a loading dose. The analysis showed that a loading dose of at least 1,200 mg twice-daily on the first treatment day followed by 600 mg twice-daily on subsequent days optimized the antibacterial effect of CEM-102. This provides the rationale for the unique loading dose regimen employed in the ongoing Phase 2/3 clinical trial to minimize bacterial resistance and optimize efficacy.
"Antibiotic-resistant S. aureus strains are an increasing therapeutic problem both in the community as well as in the hospital setting," said Prabhavathi Fernandes, Ph.D., chief executive officer of Cempra Pharmaceuticals. "New treatment alternatives are in great need, particularly agents that are safe, administered orally, and can prevent patients from being admitted to the hospital. The potent anti-staph activity of CEM-102, its long safety record and low incidence of resistance make it a highly promising anti-MRSA drug candidate."
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