Aradigm Corporation has announced that top-line results from the Phase 3 ORBIT-3 and ORBIT-4 trials of Pulmaquin inhaled ciprofloxacin for the treatment of P. aeruginosa lung infections in patients with non-cystic fibrosis bronchiectasis (non-CF BE) demonstrated increase in time to the first exacerbation, the primary endpoint, that was not statistically significant in ORBIT-3 but was statistically significant in ORBIT-4. Both studies showed statistically significant reduction in P. aeruginosa after 28 days.
The company said that it had also received results from a 2-year inhalation carcegenicity study in rats that found no increase in tumors for rats receiving Pulmaquin compared to the control group.
The primary endpoint for both trials was increase in median time to the first pulmonary exacerbation (PE), whether mild, moderate, or severe. In ORBIT-3, median time to first PE was 221 days for Pulmaquin compared to 136 days for placebo. In ORBIT-4, the median time to first PE was 230 days for the Pulmaquin group compared to 163 days for placebo. Despite the similarity of the results, the increase was statistically significant only for ORBIT-4.
The main secondary efficacy endpoint for both trials was the frequency of PEs for the Pulmaquin treatment group over 48 weeks compared to placebo. For ORBIT-3, there was a 13% reduction in the frequency of PEs for the Pulmaquin group, which was not statistically significant. Patients in the ORBIT-4 trial who received Pulmaquin had a 37% reduction in the frequency of PEs compared to the placebo group, which was statistically significant.
The design of the two trials was the same except that ORBIT-4 included a PK sub-study. In both trials, there were no differences in lung function changes for the treatment groups, and the rate of treatment emergent adverse effects and deaths unrelated to treatment were similar for both Pulmaquin and placebo groups.
Aradigm suggested that stratified analyses of the data, which were called for in the statistical analysis plan, may have been inappropriate due to an insufficient number of subjects in some of the strata. The treatment groups were stratified by gender, smoking status, and frequency of exacerbations prior to the trial.
For ORBIT-3, 89% of patients offered the opportunity to continue treatment with Pulmaquin after the 48-week double blind period continued treatment, and 91% of ORBIT-4 patients elected to continue receiving Pulmaquin.
Aradigm Chief Medical Officer Juergen Froehlich said, “We sincerely thank all of the patients and investigators who participated in these studies for their commitment. We are 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. We will review the next steps towards an application for approval of Pulmaquin in the US at an upcoming meeting scheduled with FDA and are planning to engage soon in discussions of these results with the EMA as well.”
Read the Aradigm press release.
