Advanced Life Sciences Holdings, Inc. announced positive results from Trial CL-06, the first of two pivotal phase 3 clinical trials designed to assess the safety and effectiveness of cethromycin, a novel once-a-day antibiotic, for the treatment of community acquired pneumonia (CAP).
In the study, cethromycin achieved non-inferiority in its primary endpoint of per protocol clinical cure rate compared to Biaxin (clarithromycin) in CAP. Cethromycin was evaluated using a 300 mg once-daily dosing regimen compared to 250 mg twice-daily dosing for Biaxin(R), both over a seven-day course of therapy. Cethromycin also demonstrated safety results that were similar to those seen with Biaxin.
"We are pleased with the positive results from Trial CL-06 and we believe the strong clinical cure rates coupled with the favourable safety profile seen with cethromycin in this study validate our dosing strategy and will allow us to continue on our current regulatory and commercial partnering pathway," said Dr. Michael T. Flavin, chief executive officer. "Non-inferiority was achieved despite the unusually high clinical cure rate observed with the comparator drug." Dr. Flavin added, "We are currently compiling the results from Trial CL-05, our second Phase 3 trial, and we will report top-line results when they are available."
Trial CL-06 was a multi-centre, multi-national, double-blind, randomized, comparator Phase 3 clinical study in which cethromycin was compared to Biaxin in treating mild-to-moderate CAP. In the study, 522 adult patients were enrolled from clinics in Europe, South America and Israel.
In the study, cethromycin achieved non-inferiority in its primary endpoint of per protocol clinical cure rate compared to Biaxin in CAP (cethromycin 91.5% (205/224) compared to Biaxin 95.9% (212/221) [-9.1, +0.3], p=0.0775). Cethromycin's achievement of a 91.5% clinical cure rate is consistent with its Phase 2 clinical trial results at the same 300 mg once-daily dose for CAP. The comparator drug, Biaxin, achieved a cure rate higher than the historical rate observed in any reported Biaxin CAP clinical trials to date.
Cethromycin also achieved positive safety results in the study. Cethromycin demonstrated an improved safety profile when compared with the results seen in its previous clinical trials. Additionally, 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 5.0%, Biaxin 4.6%), headache (cethromycin 3.1%, Biaxin 6.5%), nausea (cethromycin 2.7%, Biaxin(R) 3.8%), vomiting (cethromycin 2.7%, Biaxin 1.5%), abdominal pain (cethromycin 1.5%, Biaxin 3.1%) and taste disturbance (cethromycin 11.1%, Biaxin 6.2%). No drug-related serious adverse events were observed in any study subject. Liver function tests and electrocardiogram monitoring demonstrated no significant differences between subjects receiving cethromycin and subjects receiving Biaxin, consistent with the hepatic and cardiac side effect profile reported in cethromycin's previous clinical trials.
Cethromycin is not approved as a treatment for CAP, and data from this analysis have not been reviewed by the FDA. No further details of the clinical study will be available until all data analyses are complete and results are presented in a public, scientific forum.
The Phase 3 CAP clinical trial program is comprised of two randomized, well controlled, double-blind, 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 has enrolled patients from North America and South Africa. Cethromycin was evaluated using a 300 mg once-daily dosing regimen compared to 250 mg twice-daily dosing for Biaxin, both over a seven-day course of therapy. Biaxin is an FDA-approved macrolide antibiotic currently indicated for the treatment of CAP.
The primary endpoint for both trials is 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 and chest X-ray as evaluated by an independent radiologist. Extensive electrocardiogram and liver function test monitoring were incorporated into the study design to examine safety in these areas, and to build on the safety database established in previous cethromycin clinical trials.
Each trial was powered to demonstrate non-inferiority at the 95% confidence interval. To achieve non-inferiority a drug must show that it does not statistically perform any worse than the comparator treatment.
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 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 has also been shown to be effective in animal studies 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 FDA has not yet approved the drug for marketing in this or any other indication.
Advanced Life Sciences is a biopharmaceutical company engaged in the discovery, development and commercialization of novel drugs in the therapeutic areas of infection, cancer and inflammation. The COMPANY'S lead candidate, cethromycin, is a novel once-a-day antibiotic in late-stage clinical development for the treatment of respiratory tract infections including CAP.