CHICAGO, IL, November 15, 2007, 2007/PRNewswire/: -- Advanced Life Sciences Holdings, Inc. (Nasdaq: ADLS), today 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% of patients with CAP, compared to Biaxin (clarithromycin), a current standard of care treatment for CAP, which cured 93.8% of studied patients in the per protocol population. In the modified intent to treat population, cethromycin cured 83.1% of patients and Biaxin cured 81.1%. Cethromycin also demonstrated favorable 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 of Advanced Life Sciences.
Trial CL-05 was a double-blind, randomized, multi-center, 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). Cethromycins 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 favorable 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, randomized, well controlled, multi-center, 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.
Results of Trial CL-05
In Trial CL-05, cethromycin met all efficacy endpoints and demonstrated a favorable safety profile as outlined below:
Cethromycin demonstrated a favorable 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 diarrhea (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.
Pivotal Phase III Clinical Program Results Summary:
Efficacy Trial CL-05 Trial CL-06 Pooled Results
Cethromycin Biaxin Cethromycin Biaxin Cethromycin Biaxin Confidence Interval
Per Protocol Clinical Cure Rate (PPc) 94.0%
(407/429) [-5.4, +1.2]
Modified Intent-To-Treat Clinical Cure Rate (mITT) 83.1%
(430/507) [-6.4, +2.8]
Bacteriological Cure Rate (PPb) 95.9%
Safety Trial CL-05 Trial CL-06 Pooled Results
Cethromycin Biaxin Cethromycin Biaxin Cethromycin Biaxin
Abdominal Pain 1.4%
Taste Disturbance 7.6%
AE Discontinuations 4.2%
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 program.
|Contact: Melanie Nimrodi|