Results from two Phase 3 studies show that Pulmaquin (inhaled ciprofloxacin) may be a safe and effective therapy for patients with non-cystic fibrosis bronchiectasis (non-CF BE) with chronic lung infections by the bacteria Pseudomonas aeruginosa. The drug was developed by Hayward, California-based Aradigm.
Pulmaquin is an antibiotic formulation composed of liposome encapsulated and unencapsulated ciprofloxacin. It’s used in the treatment of acute and chronic lung infections caused by several groups of bacteria, including P. aeruginosa.
In the Phase 3 studies, ORBIT- 3 (NCT01515007) and ORBIT- 4 (NCT02104245), non-CF BE patients were assigned to receive Pulmaquin or placebo once daily for 28 days, followed by 28 days off-treatment, for a series of six cycles. At the end of ORBIT 4, patients could participate in a 28-day open-label extension period.
The endpoints of the studies were the mean time to first pulmonary exacerbation (mild, moderate or severe) and the number of pulmonary exacerbations observed after treatment.
Results from the ORBIT-3 study showed that patients on Pulmaquin had a higher median time to first pulmonary exacerbation (221 days) than those in the placebo group (136 days), and a 13 percent decrease in the number of pulmonary exacerbations over the study’s period compared to the placebo group. However, these results were not statistically significant.
Patients in the ORBIT-4 study under Pulmaquin treatment also showed a higher median time to first pulmonary exacerbation (230 days) than those in the placebo group (163 days), and a 37 percent decrease in the number of pulmonary exacerbations over the study period compared to the placebo group. This time, these results were considered statistically significant.
Pulmaquin was also found to induce a significant decrease in P. aeruginosa infection after the first 28 days of treatment in both studies, an effect that was maintained throughout the follow-up period.
Researchers observed that Pulmaquin was safe and well tolerated by patients with no changes in lung function or signs of airway irritation reported between groups in both studies. The most common side effects were related to the respiratory tract and the thoracic cavity. These affected 25.7 percent of patients on Pulmaquin and 21.1 percent of patients on the placebo in the ORBIT-3 study, and 16.5 percent on Pulmaquin and 19.4 percent on the placebo in the ORBIT-4 study.
At the end of the studies, 89 percent of the ORBIT-3 patients and 91 percent of the ORBIT-4 patients participated in the extension study, in which all patients received Pulmaquin for another 28 days.
“Patients with non-cystic fibrosis BE chronically infected with P. aeruginosa have a particularly severe form of this disease,” Anne O’Donnell, MD, the investigator who conducted the North American segment of the studies, said in a news release.
“It is exciting to see that after many setbacks in the development of inhaled antibiotics to treat these patients we are finally seeing results with good safety and efficacy,” she said.
Juergen Froehlich, MD, Aradigm’s chief medical officer, said he company is “delighted that once daily inhaled Pulmaquin is demonstrating a compelling reduction of pulmonary exacerbations and persistent antibiotic activity against P. aeruginosa infections, together with a good tolerability and safety profile in our Phase 3 clinical trials, as well as no carcinogenicity in animal studies.”
He said Aradigm will review its next steps toward applying for approval of Pulmaquin at a meeting scheduled with the U.S. Food and Drug Administration (FDA) and will be discussing the results of these studies with the European Medicines Agency (EMA), as well.
Pulmaquin was granted Orphan Drug designation by the FDA to treat non-CF BE. Pulmaquin has also been designated a Qualified Infectious Disease Product (QIDP) for the treatment of non-CF BE patients with chronic P. aeruginosa lung infections, and the drug was granted FDA Fast Track designation in 2014.