Intravenous (IV) Administration of Cempra Pharmaceutical's Solithromycin (CEM-101) Demonstrates Excellent Systemic Tolerability in a Phase 1 Clinical Trial

CHAPEL HILL, N.C., May 7, 2011 /PRNewswire/ -- Cempra Pharmaceuticals, a developer of differentiated antibiotics, today announced an oral presentation showing that intravenous (IV) solithromycin demonstrates excellent tolerability and a favorable pharmacokinetic (PK) profile at IV doses up to 800 mg.  Oral administration of solithromycin also showed excellent tolerability in previously reported Phase 1 studies.  The presentation will be at the 21st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)/27th International Congress of Chemotherapy (ICC), May 7 to 10, 2011, in Milan, Italy.  Cempra will also present additional in vitro activity data on both of the company's clinical candidates, solithromycin and TAKSTA (CEM-102 or fusidic acid).

Solithromycin IV Phase 1 Study

The Phase 1 study (Abstract O-95) was a single-center, randomized, double-blind, placebo-controlled dose-escalation study in healthy volunteers.  Forty-two subjects were enrolled in the single ascending dose portion of the study and divided into seven dose cohorts of 25, 50, 100, 200, 400 and 800 mg of solithromycin and placebo.  Subjects were monitored for 48 hours post-dose for safety and PK assessments.

There were no serious adverse events or clinically significant laboratory abnormalities.  The drug candidate demonstrated a favorable PK profile in single doses up to 800 mg and achieved clinically relevant plasma concentrations of about 4 micrograms/mL.  Intravenous exposure was 1.3 to three fold higher than that observed with equivalent oral doses.

"Solithromycin is currently in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia or CABP," said David Oldach, M.D., vice president of clinical research at Cempra.  "This drug could be the first macrolide since azithromycin to offer both oral and intravenous forms of administration.  This will enable in-hospital treatment of seriously ill patients and will make possible IV to oral step-down therapy, shortening hospital stays.  We are excited about this compound because of its broad spectrum of activity including macrolide-resistant strains, its greater potency than existing macrolides and its dosing flexibility.  We look forward to advancing both IV and oral forms into the next stages of clinical development."

Solithromycin (CEM-101)

Solithromycin has shown a broad spectrum of activity and high potency against respiratory and other serious pathogens in in vitro and in vivo studies.  In vitro data from two studies presented at the conference showed that solithromycin exhibited high potency against European strains associated with CABP and exhibited stronger activity against Haemophilus influenzae compared to telithromycin.  

Biedenbach et al. (Abst. P1136) evaluated the activity of solithromycin against more than 6,300 isolates collected from 18 European countries in 2010.  Activity was tested against pathogens associated with CABP and acute bacterial skin and skin structure infections (ABSSSI), such as Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, enterococci, Streptococcus pneumoniae, Streptococcus viridians, beta-haemolytic streptococci, H. influenzae and Moraxella catarrhalis.  Solithromycin exhibited greater potency than telithromycin and clindamycin against these contemporary European pathogens commonly isolated in CABP and ABSSSI.  

Farrell et al. (Abst. P1452) investigated the activity of solithromycin against almost 1,200 H. influenzae strains acquired from patients with CABP in 24 countries as part of the SENTRY antimicrobial surveillance program from 2009.  Solithromycin had greater potency than telithromycin, with MIC50 and MIC90 values of one and two micrograms/mL, respectively. Solithromycin resistance, found in nine of the 1,198 isolates (less than one percent), was rare, and when observed was attributed to ribosomal gene mutations.

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.  Jones et al. (Abst. P944) evaluated the activity of fusidic acid against over 16,000 contemporary gram positive pathogens associated with ABSSSI isolated in the U.S. from 2008 to 2010.  Twelve thousand of these strains were S. aureus, of which 52 percent were MRSA; 2,000 strains were coagulase-negative staphylococci (CoNS); and 2,000 were beta-haemolytic streptococci (group A and B).  Fusidic acid was highly active against all ABSSSI strains including S. aureus (99.73 percent at less than 1 micrograms/mL), with both methicillin-sensitive and MRSA strains having similar sensitivity rates.  Methicillin-resistant CoNS was slightly less sensitive (90.76 percent) than methicillin-sensitive CoNS (97.28 percent). Group A streptococci (S. pyogenes) were inhibited at less than 8 mg/L. These drug levels are well below the 80 microgram/mL trough level achieved by the loading dose currently in clinical trials in the U.S.

Intracellular S. aureus can be challenging to treat as antibiotics may have difficulty reaching active concentrations.  Lemaire et al. (Abst. P780) tested the activity of fusidic acid against intracellular clinical isolates of S. aureus.  Fusidic acid was active against intracellular strains even when the strains exhibited a low level of resistance (8 micrograms/mL).  With the loading dose in clinical development in the U.S. by Cempra Pharmaceuticals, intracellular fusidic acid concentrations reach 80 micrograms/mL, which is sufficient to address these strains both intracellularly and extracellularly.

Prabhavathi Fernandes, Ph.D, chief executive officer of Cempra added, "We continue to add valuable information to the profiles of our two differentiated clinical-stage antibiotics.  Solithromycin continues to demonstrate potent activity against a broad spectrum of bacterial pathogens.  With its excellent tolerability demonstrated to date and its flexible oral and IV dosing, it is evolving into a very promising antibiotic candidate with significant potential to treat common and atypical bacterial infections.  TAKSTA continues to demonstrate potent activity against U.S. gram-positive strains.  We believe its oral dosing combined with our loading dose regimen will enable the drug to be a go-to antibiotic for serious ABSSSIs when there is benefit to keeping the patient out of the hospital.  We continue moving both programs forward in clinical development."

About solithromycin (CEM-101)

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 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
• No inhibition of the acetylcholine nicotinic receptor, unlike telithromycin; 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
• Once-daily dosing

Potential for indications beyond CABP, including urethritis and other urogenital infections, bioterrorism targets, malaria, M. avium infections and tuberculosis

About TAKSTA™

TAKSTA, (sodium fusidate) is a novel class of antibiotic with an established history of safety and efficacy outside the United States. TAKSTA is being developed as an NCE in the U.S. for ABSSSI. Clinical trials with TAKSTA employ a proprietary front-loading oral regimen designed to increase potency, increase coverage and minimize resistance development. Cempra believes that TAKSTA will be an important addition to anti-MRSA therapies based on the following:

• Sodium fusidate is orally active against gram-positive bacteria, including all S. aureus strains such as HA-MRSA and CA-MRSA
• TAKSTA employs a novel and proprietary PK-PD-based dosing regimen of sodium fusidate that optimizes efficacy and minimizes the risk of resistance development
• Sodium fusidate is the only compound within the fusidane class and therefore is unlikely to select for cross-resistance to other classes of antibiotics
• Sodium fusidate's safety has been well documented even when used for long periods of time (over one year) to treat osteomyelitis and other serious infections
• Sodium fusidate has been used safely in children including neonates in countries where it is marketed

About 60 to 80 percent of the 13 million acute skin structure infections that occur in the U.S. each year are attributed to MRSA. There is a growing need for an oral anti-MRSA drug that is safe and effective for acute illness, and is safe for long-term administration.

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-antimicrobial indications in COPD, chronic inflammatory and GI disorders. Additional information about Cempra can be found at www.cempra.com.

Media Contacts:
Robert E. Flamm, Ph.D.
Russo Partner LLC
(212) 845-4226
[email protected]

Tony Russo, Ph.D.
Russo Partners LLC
(212) 845-4251
[email protected]

SOURCE Cempra Pharmaceuticals