Cempra Pharmaceuticals' Solithromycin (CEM-101) Demonstrates Potent In Vitro and In Vivo Activity Against Malaria
- Data suggest highly potent activity against Plasmodium falciparum; IC50 lower than that of artesunate against the NF54 strain and in a mouse malaria model
- Solithromycin's broad activity spectrum further elucidated by demonstrating potent activity against Mycobacterium leprae
- Data to be presented at the American Society of Tropical
Medicine and Hygiene 59th Annual Meeting, November 3 to 7
CHAPEL HILL, N.C., Nov. 3, 2010 /PRNewswire/ -- Cempra Pharmaceuticals today announced abstracts to be presented on its novel fluoroketolide antibiotic, solithromycin (CEM-101), at the American Society of Tropical Medicine and Hygiene 59th Annual Meeting, November 3 to 7 in Atlanta. The abstracts will present new information on solithromycin's antimalarial activity. Additional data will demonstrate activity against Mycobacterium leprae.
Solithromycin is a fluoroketolide belonging to the macrolide class and is the first macrolide since azithromycin with the potential for both IV and oral administration. The compound has potent in vitro activity against respiratory pathogens such as pneumococci, including macrolide-resistant strains. It has also shown potent activity against a broad range of pathogens including community-acquired methicillin-resistant Staphylococcus aureus, M. avium, enterococci and gonococci. Research to be presented at this conference will further define solithromycin's broad activity spectrum against important human pathogens.
"Solithromycin has so far demonstrated impressive potency and activity spectrum against a wide range of human pathogens," said Prabhavathi Fernandes, president and chief executive officer of Cempra. "Malaria is a very serious and prevalent infection in many parts of the world. Increasing resistance to current therapies necessitate the development of new drugs to treat it. Results from these studies suggest that solithromycin is a very promising anti-malarial candidate. These results also add to the expanding activity and tolerability profile of the compound, which is in Phase 2 clinical trials for community-acquired bacterial pneumonia."
Solithromycin demonstrates potent in vitro and in vivo activity against malaria
Two studies support the potential of solithromycin as a potent anti-malarial agent. Craft et al. (Abst. # 269) tested the activity of solithromycin against different Plasmodium species. The compound was tested against intra-erythrocytic forms of P. falciparum derived from cultured NF54 strains. Following a 120 hour exposure period, solithromycin showed an IC50 of 2.4 ng/ml compared to 3.3 ng/ml for artesunate and 5.3 ng/ml for clindamycin. Based on this activity, solithromycin was tested in a mouse P. berghei infection model. Antiparasitic activity following a single dose of 100 mg.kg of solithromycin was about 80% and mouse survival was between 12 and 15 days depending on the vehicle used. Following daily 100 mg daily doses of solithromycin, anti-parasitic activity reached almost 100% and the mice survived for 30 days, which is considered fully curative. These data demonstrate the high activity of solithromycin against malaria and its potential for treating this disease.
In a second study, Fracisco et al. (Abst. #265) investigated the activity of solithromycin in both blood stage treatment and causal prophylactic mouse (targets the initial liver stage) models against P. berghei infection. In both cases, a minimum curative dose was identified without any evidence of toxicity. In the blood stage treatment model, subcutaneous administration of 40 mg/kg/d for three days and oral administration of 80 mg/kg/d for three days was curative. In the causal prophylaxis model, the minimum curative dose for both subcutaneous and oral administration was 40 mg/kg/d for three days. Importantly, no systemic toxicity was observed with either dosing route at doses as high as 160 mg/kg/d for three days.
Solithromycin's activity spectrum continues to expand: demonstrates activity against Mycobacterium leprae
Solithromycin has shown activity that is 8 to 16 times more potent than other macrolides. It has also demonstrated a broad activity spectrum demonstrating activity against respiratory pathogens, including macrolide-resistant strains, and a variety of other important pathogens.
Lahiri et al. (Abst #1137) investigated solithromycin's activity against the Thai-53 isolate of M. leprae in an in vitro model and in an intracellular peritoneal macrophage model. A concentration of 0.15 ug/ml was able to reduce viability of the pathogen compared to controls. These results indicate that solithromycin might be a promising candidate to treat leprosy.
About solithromycin (formerly CEM-101)
Solithromycin is the first fluoroketolide with a number of attributes that may provide clinically important advantages over several comparator products:
8 to 16 times more potent than azithromycin and is active
against organisms that have become resistant to azithromycin
Potent in vitro activity against all important respiratory pathogens, including pneumococci, beta-hemolytic streptococci, staphylococci, Hemophilus, 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 trials of the oral formulation
Low resistance frequency in vitro
Unlike telithromycin, solithromycin does not inhibit the alpha-7 acetylcholine nicotinic receptor; such inhibition 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
Potential for indications beyond CABP, including urethritis and other urogenital infections, bioterrorism targets, malaria, M. avium infections and tuberculosis.
The annual incidence for CABP in the United States is over five million of which over 1 million are hospitalized (File, T.M., Lancet, 2003; File, T.M. and Tan, J.S. JAMA, 2005; CDC, National Hospital Discharge Survey, 2006; File, T.M. and Marrie, T., Postgrad. Med., 2010). There is a growing need for new drugs to address the issues of drug resistance, tolerability, and IV administration associated with currently available treatments.
About Cempra Pharmaceuticals
Founded in 2006, Cempra Pharmaceuticals is a privately-held, clinical-stage pharmaceutical company focused on developing antibacterials to address critical medical needs. Two lead products, both in late-stage clinical trials, address the urgent and increasing need for new treatments targeting drug-resistant bacterial infections in the hospital and in the community. Cempra is well-funded and is committed to developing commercially and medically differentiated and novel products that reduce development risk and provide a high financial return. The company is also utilizing its proprietary compound library and chemistry technology to develop novel macrolides without antibacterial activity for non-antibiotic uses such as COPD, chronic inflammatory and GI disorders. Additional information about Cempra can be found at www.cempra.com.
Robert E. Flamm, Ph.D.
Russo Partners, LLC
Tony Russo, Ph.D.
Russo Partners, LLC
SOURCE Russo Partners, LLC
Posted: November 2010