Positive results for potential new antibiotic

CHAPEL HILL, N.C.—Cempra Inc., a clinical-stage pharmaceutical company focused on developing antibiotics in the face of rising antibiotic resistant bacterial infections, announced recently the publication of positive results from its pivotal Phase 3 clinical trial of solithromycin oral capsules in the treatment of patients with community-acquired bacterial pneumonia (CABP) in The Lancet Infectious Diseases.

Solithromycin, Cempra says, is a highly potent next-generation macrolide—the first fluoroketolide, in fact—which has activity against the common CABP pathogens and macrolide-resistant bacterial strains. In-vitro and in-vivo studies have shown potent activity against Streptococcus pneumoniae as well as an extended spectrum of activity against community-associated methicillin-resistant Staphylococcus aureus, streptococci, Haemophilus influenzae, enterococci, Mycobacterium avium and in animal models of malaria.

It is also active against atypical bacteria, such as legionella, chlamydia, mycoplasma and ureaplasma, as well as against gonococci and other organisms that cause genitourinary tract infections. It is reportedly eight to 16 times more potent than azithromycin and is active against azithromycin-resistant strains. Solithromycin's activity against resistant strains is driven by its ability to interact with three sites on the bacterial ribosome, compared to one or two for current macrolides, the company says—binding to three ribosomal sites is expected to limit resistance development.

The article documenting the recent Phase 3 data, titled “Efficacy and safety of oral solithromycin versus oral moxifloxacin for the treatment of community-acquired bacterial pneumonia: a global, double-blind, multi-centre, randomized, active-controlled, non-inferiority trial (SOLITAIRE-ORAL)” appeared in the Feb. 4 online issue of The Lancet Infectious Diseases and will be published in a subsequent print issue of the journal.

“Pneumonia remains a top-10 cause of death in the U.S. and is the leading cause of death from infectious disease in most developed countries. The management of CABP is challenged by increasing antimicrobial resistance, which is approaching 50 percent in the U.S,” said Dr. Carlos M. Barrera, principal investigator and a pulmonologist and endocrinologist at Baptist Hospital of Miami. “The results of this study are exciting because solithromycin demonstrated efficacy comparable to moxifloxacin, with a safety profile similar to the most widely-used macrolide antibiotics. This shows the potential to restore the use of macrolide monotherapy for CABP.”

In the intent-to-treat population of this study, solithromycin met the primary objective of statistical non-inferiority to oral moxifloxacin for the treatment of CABP with a treatment success rate at the early clinical response (ECR, 72 hours after the first dose of study drug) of 78.2 percent for solithromycin and 77.9 percent for moxifloxacin. The 95-percent confidence interval for the treatment difference had lower and upper bounds of -5.5 percent and 6.1 percent, respectively.

Treatment-emergent adverse events were comparable for the two patient groups with 155 (36.6 percent) reported for solithromycin and 154 (35.6 percent) for moxifloxacin. There were no serious adverse events attributed to solithromycin. In addition, there were two cases of Clostridium difficile infection, both of which occurred in the moxifloxacin group.

“SOLITAIRE-ORAL is a landmark study and a significant achievement, as solithromycin is the first new oral CABP drug studied in a global, pivotal Phase 3 study in more than a decade,” stated Dr. Prabhavathi Fernandes, president and CEO of Cempra. “We are extremely pleased that The Lancet Infectious Diseases has chosen to publish these data in their journal.”

In October, Cempra announced successful results of the second Phase 3 pivotal trial of solithromycin that used an intravenous formulation (Solitaire-IV), and has begun and is planning to complete a rolling New Drug Application submission to the U.S. Food and Drug Administration (FDA) for the oral and intravenous formulations for the treatment of CABP during the first half of 2016. The FDA has granted Fast Track designation for solithromycin IV and capsules for the treatment of CABP. The agency has also designated solithromycin IV and capsules for the treatment of CABP as a Qualified Infectious Disease Product.

Community-acquired bacterial pneumonia is, Cempra notes, the No. 1 cause of death from an infection, particularly in the very young and in the elderly. CABP is one of the most commonly diagnosed bacterial infections in the United States, resulting in 5 million to 10 million cases per year. Although many strains of the primary CABP pathogen, Streptococcus pneumoniae, are resistant to currently-approved macrolides, this class of antibiotic remains among the most commonly prescribed for CABP in both the hospital and community settings. Due to the rising threat of microbial resistance, along with concerns over antibiotic tolerability and impact on intestinal microflora, new CABP treatments are needed, Cempra points out, adding that antibiotic resistance is a complex, emerging problem globally with potentially devastating consequences for public health.

Cempra is focused on developing antibiotics to meet critical medical needs in the treatment of bacterial infectious diseases. Cempra’s two lead product candidates are currently in advanced clinical development. Solithromycin (currently designated as CEM-101) has successfully completed two Phase 3 clinical trials for CABP and is licensed to strategic commercial partner Toyama Chemical Co. Ltd., a subsidiary of FUJIFILM Holdings Corp., for certain exclusive rights in Japan. Solithromycin is also in a Phase 3 clinical trial for uncomplicated urogenital urethritis caused by Neisseria gonorrhoeae or chlamydia. Cempra is contracted with the U.S. Biomedical Advanced Research and Development Authority for the development of solithromycin for pediatric use. Three formulations—intravenous, oral capsules and a suspension formulation—are in a Phase 1b trial in children from birth to 17 years of age.

Taksta is Cempra's second product candidate, which is being developed for acute bacterial skin and skin structure infections and is also expected to be tested in an exploratory study for chronic oral treatment of refractory infections in bones and joints.

Both products seek to address the need for new treatments targeting drug-resistant bacterial infections in the hospital and in the community. Cempra, which was founded in 2006, has also synthesized novel macrolides for non-antibiotic uses, such as the treatment of chronic inflammatory diseases, endocrine diseases and gastric motility disorders.