Advanced Life Sciences Holdings Inc. is proceeding with its new drug application (NDA) for cethromycin in community-acquired pneumonia (CAP) after results of the second of two pivotal clinical trials showed that the ketolide antibiotic met its primary endpoint of statistical noninferiority cure rates.
In a double-blind, randomized, multicenter, multinational Phase III clinical trial of 584 adults in the U.S., Canada, and South Africa, cethromycin cured 94 percent of patients with CAP, compared with 93.8 percent of patients cured with Biaxin (clarithromycin), the company reported Thursday.
Biaxin, an FDA-approved antibiotic made by Abbott Park, Ill.-based Abbott, is considered the standard of care for the treatment of CAP, which affects more than 5 million Americans each year and is the sixth leading cause of death.
In the modified intent-to-treat population, cethromycin cured 83.1 percent of patients and Biaxin cured 81.1 percent in the most recently reported study, known as CL-05. Participants received a seven-day course of cethromycin 300 mg once-daily or a 250 mg twice-daily dosing regimen of Biaxin.
In addition to achieving its endpoint, cethromycin demonstrated favorable safety results, with reported adverse effects similar to or less than those seen with Biaxin, CEO Michael Flavin said during a conference call.
The results of the study, Flavin said, represent the achievement of the firm's primary objective of developing cethromycin as a treatment for CAP "to address the critical need for new antibiotic therapies that can overcome growing bacterial resistance without causing collateral damage, such as Clostridium difficile-associated disease."
The primary endpoint for CL-05 and CL-06 was the clinical cure rate at the test-of-cure visit, days 14-21 after the start of dosing, said David A. Eiznhamer, Advanced Life's executive vice president of clinical development.
The incidence of adverse events was not statistically different between cethromycin and Biaxin in both trials, he said, adding that the most common adverse events reported in patients receiving cethromycin were mild-to-moderate diarrhea, headache, nausea, vomiting, abdominal pain and taste disturbance.
No drug-related serious adverse events were observed in either study, Eiznhamer added.
With the clinical development stage of its program successfully concluded, Flavin said, Advanced Life is turning its attention to the commercialization of cethromycin.
"We believe the positive results from trials CL-06 and CL-05 will form the basis of a strong NDA submission in the near future," he said.
The firm is focusing on engaging a commercial partner with a sales force large enough to target primary care physicians. "With data in hand, we can accelerate this process," Flavin noted.
Company consultant Donald Low, chief of the department of microbiology at Mount Sinai Hospital in Toronto, said that, more than ever, there is a need for a new class of antibiotics to treat community-acquired bacterial infections.
With life-threatening strains of drug-resistant bacteria spreading in the community, such as Streptococcus pneumoniae A-19, C. difficile colitis and methicillin-resistant Staphylococcus aureus USA300, physicians are placing their hopes in new agents like cethromycin as cures, said Low, an expert in infectious diseases and antimicrobial resistance who was involved in identifying severe acute respiratory syndrome, better known as SARS, during the 2003 outbreak in Toronto.
"Although we still have good drugs available, that list is becoming shorter and shorter," he said.
In addition to the CAP indication, Advanced Life is investigating cethromycin as a prophylactic postexposure treatment for inhalation anthrax.
The FDA has granted orphan drug designation to cethromycin for the anthrax indication.
Shares of Advanced Life (NASDAQ:ADLS) rose 3 cents Thursday to close at $1.93.