Aradigm Corporation, a pharmaceutical company focused on the development and commercialization of drugs for the prevention and treatment of severe respiratory diseases, recently announced the conclusion of patient enrollment in the ORBIT-3 trial, the second of the two fully enrolled Phase III pivotal studies of the company’s formulation of inhaled ciprofloxacin Pulmaquin®, to treat patients with a diagnosis of non-cystic fibrosis bronchiectasis (non-CF BE) who are chronically infected with Pseudomonas aeruginosa.
Bronchiectasis features permanently dilated airways caused by chronic bronchial inflammation secondary to inappropriate clearance of various micro-organisms and recurrent infections in the lungs. Infections with Pseudomonas aeruginosa are associated with an approximately 3-fold increased risk of death and an increase in both exacerbations and hospital admissions. Non-CF BE, for which there are no approved drugs, affects nearly 110,000 people in the United States and approximately 200,000 people in Europe.
ORBIT-3 is a global, placebo-controlled, double-blind, pivotal clinical trial that enrolled a total of 280 patients across 17 countries, including Australia, New Zealand, the U.S., Canada, Israel, Taiwan, South Korea, South Africa and European countries.
“We urgently need evidenced-based treatments for non-CF BE patients with recurrent respiratory infections with Pseudomonas aeruginosa who have reduced life expectancy and poor quality of life,” said Dr. Charles Haworth, MD, Clinical Director, Thoracic Medicine, Papworth Hospital, Cambridge, UK, and the principal investigator for the non-US segments of Aradigm’s Phase 3 bronchiectasis program. “The ORBIT-3 and 4 trials are an important development towards the goal of meeting the needs for effective and safe antibiotic treatment options in this severely affected patient population.”
“Our global collaboration to identify and quantify the burden of bronchiectasis for individual patients and the national healthcare systems has raised the awareness of the need to find more effective treatments for this serious medical condition,” said Dr. Timothy Aksamit, MD, Chairman, United States Bronchiectasis and Nontuberculous Mycobacteria Research Registry, and Pulmonary Consultant at Mayo Clinic, Rochester, MN. “I am very pleased to support the worldwide effort to develop Pulmaquin as a potential new treatment to reduce pulmonary exacerbations and reduce the high morbidity in these patients.”
The Phase III clinical program for Pulmaquin, a dual release formulation of liposomal, encapsulated and unencapsulated ciprofloxacin in patients with BE, includes two global, double-blind, placebo-controlled pivotal clinical studies, ORBIT-3 and ORBIT-4, similar in their protocol except for a pharmacokinetics sub-sanalysis that is going to be conducted in one of the clinical studies.
Each trial involves a 48-week, double-blind dosing regimen period of 6 cycles of 28-day on/off treatment either with a placebo or with Pulmaquin. This will be followed by a 28-day open label extension clinical study in which all patients will be treated with Pulmaquin. The superiority assessment of Pulmaquin versus the placebo during the double blind study phase will be calculated in terms of the time of first exacerbation (the study primary outcome). The secondary outcomes are pulmonary exacerbations reduction, involving severe episodes, and quality of life improvements. Lung function is being examined as a safety indicator.
Effectively treating non-CF BE patients with Pseudomonas aeruginosa remains a major unmet medical need for those with the condition. Should Pulmaquin continue to show promise in treating this prevalent infection, its eventual approval could offer this patient population a much-needed therapy for improving outcomes and quality of life.