Additional data on safety, tolerability of Cempra's solithromycin to be presented at 51st ICAAC

Cempra Pharmaceuticals today announced abstracts to be presented on its fourth generation macrolide and novel fluoroketolide antibiotic, solithromycin (CEM-101), at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17 to 20, 2011, in Chicago.  The abstracts provide additional data that demonstrate the safety and routes of administration of CEM-101, a new generation macrolide.  

CEM-101 is a fluoroketolide belonging to the macrolide class and is the first macrolide since azithromycin with the potential for both intravenous (IV) and oral administration. The compound has potent in vitro activity against respiratory pathogens such as pneumococci, including macrolide- and quinolone-resistant strains.  Bacterial pneumonia caused by multi-drug resistant pneumococci has a significant impact on morbidity and mortality due to high treatment failure rates and subsequently increases hospitalization and healthcare costs. CEM-101 has completed Phase 2 trials in community-acquired bacterial pneumonia (CABP) for the oral dosage form and is in Phase 1 for the IV dosage form.

"Data presented at this year's ICAAC conference contributes additional data on the safety, tolerability and dosing profile of our fourth generation macrolide, CEM-101," said Prabhavathi Fernandes, Ph.D., president and chief executive officer of Cempra.  "Our efforts are centered around developing an injectable macrolide that -- causes less pain on injection than traditional macrolides and that provides physicians with the possibility of initiating patients on an antibiotic in the hospital then stepping down therapy to oral administration to send the patient home on the same antibiotic.  In addition, we have extended the structure-side effect relationships of our studies on telithromycin's (Ketek®) nicotinic acetylcholine receptor activity to examine drugs outside the macrolide class.  This study links visual changes to inhibition of nicotinic acetylcholine receptor binding by certain triazole antifungals.  It provides further support for the results previously reported for the possible cause of the visual accommodation effects seen with telithromycin while CEM-101, as well as older macrolides, have not demonstrated significant receptor antagonistic activity."  

CEM-101 can be administered intravenously without pain in a rabbit ear vein model

Macrolides are a potent class of antibiotics that have been valuable for treating respiratory infections.  However, because they have been available usually as orally-administered agents their use has been generally limited to the community setting.  Erythromycin and azithromycin has been available in the U.S. as an intravenous form but their use has been limited because of pharmacologically-related pain on injection.  Fernandes et al. (Abst. A2-036) investigated the level of pain caused by infusion of CEM-101 as single or multiple doses compared to azithromycin into rabbit ear veins.  In the single-dose study, they found that of up to 3 mg/ml of CEM-101 did not elicit a pain response at infusion rates of up to 4 ml/min.  In contrast, rabbits injected with IV azithromycin (2 mg/ml), the dose approved for hospital administration, exhibited strong movements that are associated with a pain response.

In the multidose study, CEM-101, infused at concentrations of two and three mg/ml, did not generate a pain signal for up to five days of administration.  Injection site reaction was noted on days three through five but a similar response was observed when only the formulation vehicle was injected.

Further evidence that inhibition of specific nicotinic acetylcholine receptors may be responsible for some of the adverse events seen with telithromycin

Side effects caused by the ketolide, telithromycin, including reversible blurred vision, muscle weakness and liver failure were related to inhibition of the alpha7 and the ganglionic alpha3beta4 nicotinic receptor.  CEM-101 and other macrolides did not show the high level of inhibition demonstrated by telithromycin and those macrolides do not evoke telithromycin-associated adverse events.  Bertrand et al (Abst. A2-588) investigated activity of triazole antifungal agents, members of which do exhibit some side effects similar to telithromycin.  The authors demonstrated that voriconazole, which possesses a pyrimidine moiety and has been associated with visual disturbances, inhibits the ganglionic alpha3beta4 nicotinic acetylcholine receptor.  Fluconazole, which does not contain a pyrimidine moiety and is not associated with visual disturbances, does not.