The first of two Phase III pivotal trials of cethromycin from Advanced Life Sciences Holdings Inc. in community-acquired pneumonia met its primary endpoint of non-inferior cure rates compared to an approved antibiotic.
The endpoint was met despite the comparator agent, Abbott Laboratories' macrolide antibiotic Biaxin (clarithromycin), demonstrating a clinical cure rate of 95.9 percent, which Advanced Life officials said was the highest ever reported with that drug. Historically, Biaxin's clinical cure rate is between 89 percent and 91 percent, said Advanced Life President John Flavin.
The clinical rate for cethromycin, a ketolide antibiotic, in the 522-patient study was 91.5 percent, lower than in the Biaxin arm but not in a statistically significant manner (p=0.0775). There was not a significant difference in safety between the study groups, and Advanced Life said the cethromycin safety profile was improved versus that seen in earlier studies.
The double-blind study, named Trial CL-06, was run in Europe, South America and Israel. Clinical cure rates relate to the resolution of clinical signs and symptoms and improvements in chest X-rays, a week or two after completion of a seven-day treatment course. Both drugs are oral agents, with Biaxin dosed twice a day and cethromycin once.
Analyses on certain secondary endpoints, such as bacteriological cure rates, had not been completed, Flavin said.
The second Phase III study, named Trial CL-05, is expected to report in the "next several weeks," Flavin said. That trial is identically designed, except that it is being run at sites in North America and South Africa.
Flavin told BioWorld Today the goal is to file a new drug application in community-acquired pneumonia by the end of this year, and also to secure a marketing partner in that time frame.
"We are very focused on continuing along the regulatory pathway and ideally bringing this drug to the marketplace if we are successful," Flavin said. "We believe there is a desperate need for new antibiotics that can address the emerging resistance to currently marketed agents. The competitive field has narrowed while resistance has increased. That creates an opportune situation for our drug. We think are in the right place at the right time with the right product."
Flavin said the CAP market in the U.S. is about $2 billion, and includes macrolides, penicillins and one ketolide agent, Ketek (telithromycin) from Sanofi-Aventis Group. The worldwide market is $4 billion, he said.
Advanced Life is aiming to get 20 percent of the U.S. market, or $400 million in sales, by 2013, Flavin said. He said the hope is that the cethromycin eventually would be used not only in overcoming resistance, but also as part of first-line therapy.
How much of those revenues would go to Advanced Life's bottom line will be determined when a partnership is established. Flavin said discussions are ongoing with multiple potential partners.
"Our goal," Flavin said, "is to work with a large pharmaceutical partner that has a primary care physician sales force," while ideally retaining certain co-promotion rights in the U.S., such as to a subset of specialists that could include infections disease doctors, pulmonologists and allergists.
Interestingly, Advanced Life obtained worldwide rights to cethromycin in late 2004 from Abbott, the owner of the comparator drug in the pivotal program. Abbott, of Abbot Park, Ill., remains entitled to cethromycin-related milestone and royalty payments.
Flavin said the clinical cure rate of 91.5 percent in the cethromycin arm of the CL-06 trial was encouraging because it reinforced the 92 percent rate seen in Phase II studies.
While data remained blinded in the CL-05 study, the overall data on safety and cure rates appear to be positive. Flavin said the overall cure rate in the study is more than 90 percent, though he does not know the numbers from the individual arms. The safety data appear to be consistent, too, he said.
Even with the record cure rate for Biaxin, Flavin said, "We want to convey that despite its positive results we hung in there and achieved our ultimate goal." He added that cethromycin also performed well on the clinical cure endpoint when compared to all approved CAP agents, which average 89 percent to 91 percent.
Advanced Life reported cash of $22.1 million as of March 31 and an expected loss of $7.5 million to $8.5 million this quarter. Flavin said the cash position is expected to be enhanced through the up-front and milestone portions of a cethromycin marketing deal.
Separately, the company is developing cethromycin against anthrax infection. It has reported positive data from animal studies and has gained orphan designation from the FDA for the prophylactic treatment of inhalation anthrax. The product also has been studied in clinical trials in acute bacterial exacerbation of chronic bronchitis and acute bacterial sinusitis, though no trials other than CL-05 are ongoing. Among its other products, Advanced Life has open investigational new drug applications for two other agents: ALS-357 for treating malignant melanoma, for which trials are expected to begin later this year; and ALS-866, for treating inflammation-related tissue damage.
The company's shares (NASDAQ:ADLS) fell 19 cents Thursday, or 6 percent, to close at $3.