Advanced Life Sciences Holdings has announced that its novel respiratory antibiotic, Cethromycin, was shown to be effective in preventing inhalation anthrax infection.
This conclusion was reached from a primate study where a 30-day course of oral Cethromycin was 100% protective against a lethal dose of inhaled anthrax as compared to the standard of care, Cipro(R) (ciprofloxacin), which demonstrated 90% protection.
"We felt confident going into the primate study because of Cethromycin's potent activity against over 30 strains of anthrax, yet the results have exceeded our expectations," said Dr. Michael T. Flavin, Chief Executive Officer for Advanced Life Sciences. "We believe that Cethromycin's unique antibacterial properties differentiate it from other antibiotics and, if approved by the FDA, may allow it to become a useful tool in the treatment of infections such as anthrax."
Cethromycin was recently granted Orphan Drug designation by the FDA for the prophylactic treatment of inhalation anthrax and is being developed in collaboration with U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the NIH's National Institute of Allergy and Infectious Disease (NIAID). Cethromycin, which has been tested in over 4,400 human subjects, is also in pivotal Phase III trials for the treatment of community acquired pneumonia (CAP). The Company expects to report data from the CAP program in June of this year.
"With emerging bacterial resistance, both natural and engineered, there is a critical need for new antibiotics that work differently than currently available therapies to protect against anthrax," continued Dr. Flavin. "To our knowledge, there are no other antibiotics in late-stage development to address this need. Based on the human safety and animal efficacy data collected to date, we believe that Cethromycin could address this need and be considered for purchase by the U.S. Government under Project BioShield and the Strategic National Stockpile to provide protection to the American public in the event of an anthrax attack."
In the study, 30 naive non-human primates were randomized into 3 groups of 10 animals and were aerosol challenged with Ames strain anthrax spores at a target dose of 50 LD50. Beginning 24 hours post-challenge, 10 primates were treated with 16 mg/kg (the human equivalent of 300 mg) Cethromycin once daily, 10 primates were treated with 16 mg/kg ciprofloxacin twice daily, and 10 primates received water for injection (2 ml/kg) once daily. All antibiotic treatments were by oral gavage for 30 days.
The study results showed that all ten Cethromycin-treated animals survived, with one of the ten demonstrating abnormal hematologic parameters following antibiotic cessation, which were then normalized. One of the ten ciprofloxacin-treated animals died nine days following cessation of ciprofloxacin treatments after demonstrating clinical signs of infection, bacteremia and alterations in hematologic and coagulation parameters. All ten control primates demonstrated a combination of clinical signs of anthrax, bacteremia, and alterations in hematologic and coagulation parameters post-challenge with five of ten succumbing to the infection.
Advanced Life Sciences is developing Cethromycin for the prophylactic treatment of inhalation anthrax to ultimately help protect against human infection from anthrax. The primates used in the study referenced above were used to help understand anthrax disease mechanisms and to assess novel ways to treat anthrax in lieu of human efficacy testing pursuant to FDA's "Animal Efficacy Rule" (21 C.F.R. Section 314.600-650). The study referenced above was carried out in accordance with the Animal Welfare Act (AWA) under the supervision of an Institutional Animal Care and Use Committee (IACUC), which is responsible for enforcing the AWA.
The "Animal Efficacy Rule" allows for approval of new drug products based on animal data when adequate and well-controlled efficacy studies in humans cannot be ethically conducted because the studies would involve administering a potentially lethal or permanently disabling toxic substance or organism to healthy human volunteers, and field trials are not feasible before approval. Approval of a drug under the "Animal Efficacy Rule" is subject to certain postapproval commitments, including the submission of a plan for conducting postmarketing studies, postmarketing restrictions to ensure safe use (if deemed necessary), and product labeling information intended for the patient advising that, among other things, the product's approval was based on effectiveness studies conducted in animals alone.