(Liposomal Ciprofloxacin - Lipo Cip)

Development of a new way to treat chronic debilitating and life-threatening respiratory infections in cystic fibrosis.

Ciprofloxacin is approved by the FDA as an anti-infective agent in the form of tablets and injections and is widely used for the treatment of a variety of bacterial infections. We believe that delivering this potent antibiotic directly to the lung may improve its safety and efficacy in the treatment of pulmonary infections. Our novel sustained release formulation of ciprofloxacin is designed with the view that it will maintain therapeutic concentrations of the antibiotic within infected lung tissues, while reducing systemic exposure and the resulting side effects seen with currently marketed ciprofloxacin products. To achieve this sustained release, we employ liposomes, which are lipid-based nanoparticles dispersed in water that encapsulate the drug during storage and release the drug slowly in the lung. In an animal experiment, ciprofloxacin delivered to the lung of mice appeared to be rapidly absorbed into the bloodstream, with no drug detectable four hours after administration. In contrast, the liposomal formulation of ciprofloxacin produced significantly higher levels of ciprofloxacin in the lung at all time points and was still detectable at 12 hours. We also believe that for certain respiratory disease indications it may be possible that a liposomal formulation enables better interaction of the drug with the disease target, leading to improved effectiveness over other therapies. We have at present two target indications with distinct delivery systems for this formulation that share much of the laboratory and production development efforts, as well as a common safety data base.

ARD-3100 - Liposomal Ciprofloxacin for the Treatment of Cystic Fibrosis

This proprietary program using our liposomal formulation of ciprofloxacin for the treatment and control of respiratory infections common to patients with cystic fibrosis, or CF. CF is a genetic disease that causes thick, sticky mucus to form in the lungs, pancreas and other organs. In the lungs, the mucus tends to block the airways, causing lung damage and making these patients highly susceptible to lung infections. According to the Cystic Fibrosis Foundation, CF affects roughly 30,000 children and adults in the United States and roughly 70,000 children and adults worldwide. According to the American Lung Association, the direct medical care costs for an individual with CF are currently estimated to be in excess of $40,000 per year.

The inhalation route affords direct administration of the drug to the infected part of the lung, maximizing the dose to the affected site and minimizing the wasteful exposure to the rest of the body where it could cause side effects. Therefore, treatment of CF-related lung infections by direct administration of antibiotics to the lung may improve both the safety and efficacy of treatment compared to systemic administration by other routes, as well as improving patient convenience as compared to injections. Oral and injectable forms of ciprofloxacin are approved for the treatment of Pseudomonas aeruginosa, a lung infection to which CF patients are vulnerable. Currently, there is only one inhalation antibiotic approved for the treatment of this infection. We believe that local lung delivery via inhalation of ciprofloxacin in a sustained release formulation could provide a convenient, effective and safe treatment of the debilitating and often life-threatening lung infections that afflict patients with CF.
Our liposomal ciprofloxacin CF program represents the first program in which we intend to retain full ownership and development rights. We intend to commercialize this program on our own.

We have received orphan drug designation from the FDA for this product for the management of CF. As a designated orphan drug, liposomal ciprofloxacin is eligible for tax credits based upon its clinical development costs, as well as assistance from the FDA to coordinate study design. The designation also provides the opportunity to obtain market exclusivity for seven years from the date of New Drug Application, or NDA, approval.
We also intend to explore the utility of liposomal ciprofloxacin for the treatment of serious infections associated with other respiratory diseases, such as non-CF bronchiectasis.

Scientific Publications
Aradigm scientists have published extensively on aerosol formulation and pulmonary drug delivery. Following are citations relating to cystic fibrosis and/or liposomal ciprofloxacin.

Geller, D. et al.: "Bolus Inhalation of rhDNase with the AERx System in Subjects with Cystic Fibrosis" Journal of Aerosol Medicine 2003. 16(2): 175-182.

Cipolla, D. et al., Bolus Administration of INS365: Studying the Feasibility of Delivering High Dose Drugs Using the AERx® Pulmonary Delivery System, in Respiratory Drug Delivery VII, 2000, Eds. Dalby, R., et al., Serentec Press, Inc., Raleigh, NC, pp. 231-239 (2000).

Educational Links
For more information on cystic fibrosis, visit the following web sites:
Cystic Fibrosis Foundation
MedlinePlus
Cystic Fibrosis | A Support Community