CHAPEL HILL, N.C., Sept. 7, 2012 /PRNewswire/ -- Cempra Inc. (Nasdaq: CEMP), a clinical-stage pharmaceutical company focused on developing antibiotics to meet critical medical needs in the treatment of bacterial infectious diseases, today announced that data will be presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco, Sept. 9 to 12. The data will further delineate the clinical profile and activity spectrum of solithromycin, the company's late clinical-stage fluoroketolide antibiotic candidate. The data demonstrate the promising safety and tolerability profile of solithromycin as well as a pharmacokinetic-pharmacodynamic (PK-PD) analysis that will be used to support Phase 3 intravenous (IV) dose selection. Solithromycin's activity spectrum was further defined by demonstrating superior activity against Canadian isolates of Neisseria gonorrhoeae compared to azithromycin and the first study investigating solithromycin's activity against Treponema pallidum.
"Data presented at this year's conference are geared to further detailing the profile of solithromycin from both clinical and activity perspectives," said Prabhavathi Fernandes, president and chief executive officer of Cempra. "The data should be helpful when we analyze the results from our IV Phase 1 trial, which we expect to complete in the second half of 2012, and our Phase 2 trial in patients with uncomplicated gonococcal infections, which we expect to complete in the fourth quarter of this year, and in the preparation of our Phase 3 program in community-acquired bacterial pneumonia, which we expect to begin in the fourth quarter of this year."
Solithromycin safety and tolerability continues to appear promising
Solithromycin has demonstrated a favorable safety and tolerability profile when compared to levofloxacin, an antibiotic currently used to treat community-acquired bacterial pneumonia (CABP; Oldach et al., 2012). Oldach et al., (Abst. #1286; 11:15 a.m. to 1:15 P.M. PDT, Tuesday, Sept. 11) consolidated safety and tolerability data from healthy subjects and CABP patients receiving oral solithromycin from Phase 1 and Phase 2 clinical trials. No significant safety concerns emerged; most adverse events were mild. The most common adverse event that was greater than placebo or comparator agent was diarrhea (12.8 percent vs. 3.6 percent). In addition, adverse events occurred more frequently with levofloxacin than with solithromycin in the oral Phase 2 clinical trial in CABP patients. The data support the promising safety and tolerability profile of solithromycin.
Further defining Phase 3 IV dosing
Cempra plans on initiating a Phase 3 oral-to-IV step-down clinical trial of solithromycin in CABP patients in 2014, pending funding. The company has an ongoing Phase 1 clinical trial of the IV formulation in healthy subjects. Data from the IV trial will be used to determine dose for the IV treatment period in the Phase 3 trial. Okusanya et al. (Abst. #A-1269; 11:15 a.m. to 1:15 P.M. PDT, Tuesday, Sept. 11) evaluated PK data from multiple doses of both IV and oral solithromycin from Phase 1 trials and from the oral Phase 2 trial in CABP patients to refine a previously-developed population PK (PPK) model (Okusanya et al., 2010). Sufficient PK-PD target attainment probabilities were realized with IV solithromycin doses of 400 mg or 800 mg every 24 hours. A front-loading dose was not required, compared to oral administration (Okusanya et al., 2010). Data from this study will be used to support Phase 3 IV dose selection.
Solithromycin demonstrates in vitro activity against N. gonorrhoeae and T. pallidum
Antibiotic-resistant N. gonorrhoeae infections (urethritis) are an increasing public problem worldwide. Recently, the Centers for Disease Control (CDC) revised its gonococcal treatment recommendations and now no longer recommend oral cephalosporins for treatment of this infection (see MMWR, 61:590-594, 2012). New therapeutic options are needed. Cempra has initiated an open-label Phase 2 clinical trial in patients with uncomplicated gonococcal infections (see news release). In vitro activity data demonstrate that solithromycin is active against N. gonorrhoeae strains including those resistant to current antibiotics. Mallegol et al., (Abst. #E-781; 11:15 a.m. to 1:15 P.M. PDT, Monday, Sept. 10) evaluated the in vitro activity of solithromycin against N. gonorrhoeae isolated from Canada. The investigators found that solithromycin activity was at least four-fold greater than azithromycin. In addition, solithromycin was able to generate very high intracellular antimicrobial activity in an intracellular gonococcal infection model. These results further demonstrate the potential of solithromycin for treating gonococcal infections.
Macrolide resistance has been reported in some T. pallidum strains. Solithromycin, a fluoroketolide that has demonstrated activity against other macrolide-resistant pathogens, could be an option to treat some syphilis infections and for treating syphilis in penicillin-allergic patients. Molini et al., (Abst. #B-1301; 11:15 a.m. to 1:15 P.M. PDT, Tuesday, Sept. 11) tested solithromycin, azithromycin and penicillin G against wild-type and macrolide-resistant strains in a rabbit model. The latter two compounds are common recommended treatments for syphilis. The investigators found that solithromycin was as effective in treating wild type syphilis as azithromycin and penicillin G but rabbits infected with strains highly resistant to azithromycin were not cured with solithromycin.
Additional abstracts presenting data on solithromycin
Pereira D et al., Pikromycin Derivative of Solithromycin: Discussion of Activity. Abst. #F-1505, 11:15 a.m. to 1:15 P.M. PDT, Tuesday, Sept. 11. Through molecular modeling of this close analog of solithromycin, Cempra has gained insight about the chemical structures that gives solithromycin its unique ribosomal binding properties.
About CEM-101 (solithromycin)
Solithromycin is the first fluoroketolide with a number of attributes that may provide clinically important advantages over several comparator products:
- Eight to 16 times more potent than azithromycin and is active against organisms that have become resistant to azithromycin
- Potent in vitro activity against a broad range of respiratory pathogens, including pneumococci, beta-hemolytic streptococci, staphylococci, Haemophilus, Legionella, Mycoplasma, Moraxella and Chlamydophila
- Potent in vitro activity against other medically significant pathogens, including CA-MRSA, M. avium, malaria, enterococci and gonococci
- Good tolerability to date as demonstrated in Phase 1 and 2 trials of the oral formulation
- Low resistance frequency in vitro
- No pyridine sidechain, unlike telithromycin; the pyridine moiety is believed responsible for certain adverse effects observed with telithromycin (Ketek®).
- Excellent tissue distribution and intracellular tissue concentrations, including lung epithelial lining fluid and alveolar macrophages
- Oral and IV formulations concurrently in development
- Once-daily dosing
About Cempra Inc.
Founded in 2006, Cempra, Inc. is a clinical-stage pharmaceutical company focused on developing antibiotics to meet critical medical needs in the treatment of bacterial infectious diseases. Cempra's two lead product candidates have both completed oral Phase 2 clinical trials and seek to address the need for new treatments targeting drug-resistant bacterial infections in the hospital and in the community. The company also intends to utilize its series of proprietary lead compounds from its novel macrolide library for uses such as the treatment of chronic inflammatory diseases, endocrine diseases and gastric motility disorders. Additional information about Cempra can be found at www.cempra.com.
Please Note: This press release contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the results, timing, costs and regulatory review of our studies and clinical trials; our need to obtain additional funding and our ability to obtain future funding on acceptable terms; our anticipated capital expenditures and our estimates regarding our capital requirements; our ability to obtain FDA approval of our product candidates; our dependence on the success of solithromycin and Taksta; and innovation by our competitors. The reader is referred to the documents that we file from time to time with the Securities and Exchange Commission.
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