Advanced Life Sciences Holdings, Inc. announced positive results from Trial CL-05, the second of two pivotal phase III clinical trials designed to assess the safety and effectiveness of cethromycin, a novel once-a-day oral antibiotic for the treatment of mild-to-moderate community acquired pneumonia (CAP), the sixth leading cause of death in the United States.
The primary efficacy endpoint of statistical non-inferiority in the clinical cure rate at the test-of-cure visit was achieved. The study results showed that cethromycin cured 94.0 per cent of patients with CAP, compared to Biaxin(R) (clarithromycin), a current standard of care treatment for CAP, which cured 93.8 per cent of studied patients in the per protocol population. In the modified intent to treat population, cethromycin cured 83.1 per cent of patients and Biaxin cured 81.1 per cent. Cethromycin also demonstrated favourable safety results, with reported side effects similar to or less than those seen with Biaxin.
"We are very excited to have met all of our endpoints in Trial CL-05, and we are pleased to have successfully completed the clinical development program of cethromycin. The results attained in this trial, along with the positive results achieved in Trial CL-06 reported in June of this year, will form the core of our New Drug Application (NDA) submission and positions us well with prospective commercial partners," said Dr. Michael Flavin, chairman and CEO, Advanced Life Sciences.
Trial CL-05 was a double-blind, randomised, multi-centre, multi-national, comparator phase III clinical study in which cethromycin was compared to Biaxin, an approved antibiotic, in treating mild-to-moderate CAP. The trial design called for a seven-day course of therapy in which cethromycin was evaluated using a 300 mg once-daily dosing regimen compared to a 250 mg twice-daily dosing regimen of Biaxin. In the study, 584 adult patients were enrolled from clinics in the United States, Canada and South Africa.
"The need for new drugs to address CAP is imperative, as bacterial resistance rates and adverse effects continue to increase with currently approved antibiotics," said Dr. John Bartlett, Professor of Medicine in the Division of Infectious Diseases at The Johns Hopkins University School of Medicine and past President of the Infectious Diseases Society of America (IDSA). "
Cethromycin's unique mechanism of action allows it to overcome resistance and minimize adverse effects such as Clostridium difficile associated disease (CDAD) and other serious side effects. With these advantages, cethromycin may offer physicians a better treatment option for CAP. The high clinical cure rates and favourable safety profile demonstrated in the cethromycin clinical development program is evidence of the potential value of this drug to CAP patients.
"Approximately 5.6 million cases of CAP are diagnosed each year in the United States, resulting in an estimated total annual expenditure of $2 billion dollars for prescribed antibiotics to treat CAP. CAP is potentially fatal if not treated properly, and the bacteria that cause CAP are developing resistance to current standard of care treatments."
Antimicrobial resistance in important respiratory pathogens, such as the pneumococci, is a growing challenge when it comes to serious infections like CAP," said Dr. Donald Low, Head of the Division of Microbiology in the Department of Laboratory Medicine and Pathobiology at the University of Toronto in Toronto, Ontario. "Cethromycin, a new antibiotic, may be the solution to this important public health problem, as it has demonstrated a broad spectrum of antibacterial activity and an ability to overcome pneumococcal resistance in clinical trials."
The phase III CAP pivotal development program was comprised of two double-blind, randomised, well controlled, multi-centre, multi-national, comparator trials designed to assess the safety and effectiveness of cethromycin in CAP patients compared to Biaxin. Trial CL-06 enrolled patients from clinics in Europe, South America and Israel and Trial CL-05 enrolled patients from the United States, Canada and South Africa. In both trials, cethromycin was evaluated using a 300 mg once-daily oral dosing regimen compared to 250 mg twice-daily dosing for Biaxin, both over a seven-day course of therapy. Biaxin is an FDA-approved standard of care antibiotic currently indicated for the treatment of CAP.
The primary endpoint for both trials was the clinical cure rate at the test-of-cure visit (Day 14-21 post-initiation of dosing). The eligibility of patients for each trial was based on clinical signs and symptoms as well as chest X-ray results as evaluated by an independent radiologist. Extensive electrocardiogram and liver function test monitoring were incorporated into the study design in order to examine safety in these areas and add to the safety database established in previous cethromycin clinical trials.
Cethromycin demonstrated a favourable safety profile in Trial CL-05. The incidence of adverse events was not statistically different between cethromycin and Biaxin. The most common adverse events reported in patients receiving cethromycin were mild-to-moderate diarrhoea (cethromycin 4.5%, Biaxin 4.1%), headache (cethromycin 2.4%, Biaxin 3.1%), nausea (cethromycin 4.5%, Biaxin 1.4%), vomiting (cethromycin 1.4%, Biaxin 1.0%), abdominal pain (cethromycin 1.4%, Biaxin 1.4%) and taste disturbance (cethromycin 7.6%, Biaxin 2.1%). No drug-related serious adverse events were observed in any study subject. Liver function tests and electrocardiogram monitoring in Trial CL-05 demonstrated no significant differences between subjects receiving cethromycin and subjects receiving Biaxin. This is consistent with the hepatic and cardiac side effect profile reported in previous cethromycin clinical trials.
Cethromycin is not approved as a treatment for CAP, and data from this analysis have not been reviewed by the Food and Drug Administration (FDA).
"We would like to thank all the patients and principal investigators who participated in the cethromycin pivotal clinical trial program," said Dr. Flavin. "We would also like to thank our contract research organizations, Quintiles, Covance Clinical Laboratories, Covance Cardiac Safety Services and ClinPhone for their work in conducting our clinical programme."
CAP is the sixth most common cause of death in the United States. CAP and other respiratory tract infections are caused by pathogens such as Streptococcus pneumonia and Haemophilus influenzae. CAP affects 5.6 million patients in the United States each year, with 10 million physician visits and 2 million hospitalisations occurring annually.
Macrolides and penicillins are currently the front-line treatments for respiratory tract infections such as CAP. As macrolide and penicillin resistance grows and has the potential to cause more clinical failures, there is a need for new antibiotics with unique mechanisms of action that can overcome this emerging resistance.
Cethromycin has shown higher in vitro potency and a broader range of activity than macrolides against Gram-positive bacteria associated with respiratory tract infections, and, again in vitro tests, it appears to be effective against penicillin- and macrolide-resistant bacteria. Cethromycin has a mechanism of action that may slow the onset of future bacterial resistance. In addition to its utility in CAP, cethromycin is also being investigated for the prophylactic treatment of inhalation anthrax post-exposure. The FDA has designated cethromycin as an orphan drug for the prophylactic treatment of inhalation anthrax post exposure, but the drug is not yet approved for this or any other indication.
Advanced Life Sciences is a biopharmaceutical company engaged in the discovery, development and commercialisation of novel drugs in the therapeutic areas of infection, cancer and inflammation. The company's lead candidate, cethromycin, is a novel once-a-day oral antibiotic in late-stage clinical development for the treatment of respiratory tract infections including CAP.