Cempra Pharmaceuticals today announced poster presentations on its novel antibiotic CEM-101, a next-generation macrolide, and CEM-102 (TAKSTA), the company's proprietary front-loading oral dosing regimen of sodium fusidate, at the 20th European Congress of Clinical Microbiology and Infectious Disease (ECCMID), April 10 to 13, 2010, in Vienna Austria. All presentations are scheduled for 12:30 to 1:30 p.m. CET on Sunday, April 11.
CEM-101 has shown a broad spectrum of activity and high potency against respiratory and other serious pathogens in in vitro and in vivo studies. Data presented at the conference showed results from a Phase 1 multi-dose, dose escalation study in healthy subjects and data from several in vitro activity studies demonstrating the high potency and broad activity spectrum of CEM-101.
The results from the first Phase 1 dose escalation study demonstrated that doses of CEM-101 from 200 to 600 mg were safe and well tolerated in healthy subjects and that the compound's pharmacokinetic profile is supportive of once-daily dosing (Poster #902). CEM-101 was administered once-daily for seven days at 200, 400 and 600 mg. The compound showed moderate accumulation over the seven days of dosing indicating no induction of cytochrome enzymes as is seen with some other macrolides. Mild, clinically insignificant gastrointestinal side effects were the most common adverse events observed in each dose group. There were no clinically significant adverse events.
CEM-101's in vitro spectrum of activity and potency were examined against a variety of respiratory and non-respiratory bacterial pathogens. Jones et al. (Poster #901) tested CEM-101 against European clinical isolates including S. aureus, coagulase negative staphylococci, enteroccoci and S. pneumoniae. They found that CEM-101 exhibited equal to or greater potency, compared to telithromycin, and superior potency, compared to other macrolides against most pathogens causing community-acquired bacterial pneumonia (CABP) and acute bacterial skin structure infections (aBSSI). In another study (Poster #903) CEM-101 demonstrated superior activity against several serotypes of Legionella pneumophila compared to other macrolides, particularly erythromycin and azithromycin, which are commonly used to treat Legionellosis. Only levofloxacin showed comparable activity to CEM-101 in these assays.
CEM-101's increased potency results from the molecule binding to three sites on the bacterial ribosome compared to two sites for other macrolides. It has been hypothesized that the additional binding site would engender activity against pathogens resistant to available macrolides. Dubois and Fernandes (Poster #904) evaluated CEM-101's activity against drug resistant respiratory pathogens, including strains of S. pneumoniae and H. influenza. CEM-101 demonstrated superior activity against S. pneumoniae drug resistant strains including erythromycin-R mef E, erythromycin-R erm B and ciprofloxacin-R gyrA, parC. CEM-101 also demonstrated superior activity, compared to other macrolides, against erythromycin-R erm A, B, C H. influenzae.
Prophylactic treatment with antibiotics is recommended for individuals exposed to bacterial meningitis patients infected with Neisseria meningitides. Unfortunately, resistance or reduced susceptibility to antibiotics used for prophylaxis has been reported. In vitro activity of CEM-101 against invasive N. meningitides isolates, including resistant strains, was investigated (Poster #905), CEM-101 demonstrated activity comparable to ceftriaxone and the fluoroquinolones and had two to 16-fold greater activity compared to other macrolides. CEM-101 may be a potent alternative to current prophylactic therapies.
TAKSTA (CEM-102, sodium fusidate)
TAKSTA is sodium fusidate delivered with a proprietary front-loading dosing regimen to enhance spectrum of activity, optimize efficacy and reduce resistance development. Sodium fusidate has a long and established record of safety and efficacy outside the U.S. It has been reported that bacteria tend to develop resistance to sodium fusidate so the drug is usually used in combination with other drugs outside the U.S. However, this premise has been challenged. Adequate dosing determined by PK/PD calculations could be used to decrease the development of resistance. In vitro activity was analyzed in several thousand strains collected in 13 European countries (Poster #929). Despite being available for over 40 years in Europe sodium fusidate demonstrated sustained activity against S. aureus including methicillin-resistant strains indicating that the compound is not highly susceptible to resistance development. Sodium fusidate appears to provide a valuable oral treatment alternative to other anti-MRSA agents in the management of serious S. aureus infections.
"The in vitro data on CEM-101 that we presented at this year's ECCMID is very consistent with results from earlier work. The completion of the multi-dose Phase 1 study, in which the compound was very well tolerated confirms the substantial therapeutic potential of CEM-101," said Prabhavathi Fernandes, Ph.D., chief executive officer of Cempra. "The tolerability matches the profile we observed in an earlier Phase 1 single-dose study. In addition, CEM-101 continues to demonstrate high potency and a broad spectrum of activity against respiratory pathogens, including drug-resistant strains, as well as other serious pathogens. The CEM-102 data from the in vitro European isolates study is particularly gratifying because it confirms our analysis of the low resistance development potential of sodium fusidate. TAKSTA is an exceptionally promising oral anti-MRSA agent that we are developing for a high unmet clinical need in the U.S. market."