Aradigm has announced top-line results from two Phase 3 clinical trials of Pulmaquin (inhaled ciprofloxacin) for the treatment of patients with non-cystic fibrosis bronchiectasis (non-CF BE) who have chronic lung infections with Pseudomonas aeruginosa.
Pulmaquin is a dual release formulation composed of a mixture of liposome encapsulated and unencapsulated ciprofloxacin. The treatment was granted Fast Track designation by the FDA in 2014. The two Phase 3 trials, ORBIT-3 and ORBIT-4, enrolled 278 and 304 non-CF BE patients, respectively. The trials lasted for 48-weeks and were identical in design except for a pharmacokinetics sub-study that was conducted in one of the trials.
The primary endpoint, a significant increase in median time to mild, moderate or severe pulmonary exacerbation (PE) was reached in ORBIT-4 with the median time of 230 days to PE in the Pulmaquin treatment group compared to 163 days in the placebo group (statistically significant, P=0.0462). In the key secondary efficacy endpoint, there was a 37% reduction in the frequency of PEs over the 48-week treatment period in the Pulmaquin treatment group compared to the placebo group.
In ORBIT-3 the median time to the first mild, moderate or severe PE was 221 days with Pulmaquin compared to 136 days in the placebo group, however, this was deemed as not being a statistically significant difference (P=0.8488). The Pulmaquin group had a reduction of 13% in frequency of PEs over the 48-weeks when compared to the placebo group, however this was again deemed to be not statistically significant (P=0.3125).
Combining data from both studies and only examining PEs that are moderate or severe (i.e., those that required interventions with antibiotics or hospitalization) the median time to first PE in the Pulmaquin group was 302 days vs. placebo 198 days (P=0.0217).
“Patients with non-cystic fibrosis BE chronically infected with P. aeruginosa have a particularly severe form of this disease. 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,” said Dr. Anne O’Donnell, MD, Professor of Medicine and Chief, Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Medical Center, Washington DC, who was the Principal Investigator for the North American segment of the ORBIT-3 and ORBIT-4 trials.
The company stated that the next steps towards an application for approval of Pulmaquin will be reviewed in an upcoming meeting scheduled with the Food and Drug Administration.
For more information visit Aradigm.com.