Scientists from the UK Defence Science and Technology Laboratory (Dstl) report, in a preliminary study, that they have demonstrated that a single dose of Aradigm Corporation's (OTCBB:ARDM) (the "Company") liposomal ciprofloxacin formulation Lipoquin administered 24 hours after exposure to a lethal dose of the bacterium Yersinia pestis provided full protection in a murine model of pneumonic plague. In comparison, a single dose of oral ciprofloxacin administered 24 hours post-exposure provided no protection.
The Gram-negative bacterium Yersinia pestis is the causative agent of plague, a disease thought to be responsible for the death of 200 million people through devastating pandemics such as the Black Death. Inhalation of Y. pestis can result in the most severe form of the disease, pneumonic plague, which if untreated may have a mortality rate of 100%. Currently, there is no licensed vaccine for use in humans.
In the study, the animals were followed for up to 28 days post-exposure. Exposure to aerosolized Y. pestis was lethal with all untreated mice succumbing to a systemic infection by day 3 post-exposure. A single dose of oral ciprofloxacin administered at 24 hours post-exposure did not prevent mortality and only increased the mean time to death to 5 days compared to 3 days for untreated mice. In comparison, a single dose of Lipoquin delivered via the nose into the lungs of the animals provided 100% protection and significantly improved survival compared to a single dose of oral ciprofloxacin (P<0.0001); a single dose of aerosolized Lipoquin administered at 24 hours post-exposure provided approximately 70% protection and significantly improved survival when compared to a single dose of oral ciprofloxacin (P<0.001).
In their report, the scientists state that the study demonstrated the superior efficacy of Lipoquin compared to oral ciprofloxacin as post-exposure prophylaxis against Y. pestis.
Scientists at Dstl previously demonstrated the efficacy of Lipoquin compared to oral ciprofloxacin against Francisella tularensis (the causative agent of tularemia) infection using the highly virulent SCHU S4 strain: a single dose of aerosolized Lipoquin provided full protection against lethal exposure in a murine model of F. tularensis infection. In addition, a single dose of aerosolized Lipoquin was superior to a five-day course of twice-daily oral ciprofloxacin therapy, which provided only minimal protection.
Additionally, in a previously reported collaborative study with the Health Protection Agency and Dstl, Aradigm's inhaled liposomal ciprofloxacin was shown to be effective in a mouse model against Coxiella burnetii - the causative agent of the disease Q fever. C. burnetii is endemic worldwide, infects a wide variety of animals and humans and has a low infectious dose by the inhalational route. Clinical presentation in humans may lead to an acute infection with flu-like symptoms, or a chronic life-threatening disease. A recent epidemic of Q fever in humans took place in the Netherlands in 2009, with 2,357 reported cases and 6 deaths. Current oral antibiotic treatment of Q fever can be lengthy and complex.
"We are very excited to see that our inhaled liposomal ciprofloxacin has been found to show very promising efficacy against three possible bioterrorism agents, making it potentially a useful broad-spectrum prophylaxis and treatment against such infections. We continue to seek opportunities for additional funding for this type of work via collaborations with government agencies with the view that our liposomal ciprofloxacin may be approved under FDA and similar overseas regulations relating to new drugs or biologics for potentially fatal diseases where human studies cannot be conducted ethically or practically," said Igor Gonda, President and CEO of Aradigm.