Linhaliq filed with the EU for non-cystic fibrosis bronchiectasis.- Aradigm.

Aradigm has submitted its Marketing Authorisation Application (MAA) to European Medicines Agency (EMA) for Linhaliq (ciprofloxacin inhaled) for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic lung infection with Pseudomonas aeruginosa (P. aeruginosa).

Linhaliq was evaluated in two Phase III studies (ORBIT-3 and ORBIT-4) to determine its safety and effectiveness as a once- a-day inhaled formulation for the chronic treatment of patients with NCFBE who have chronic lung infections with P. aeruginosa. In ORBIT-4 the median time to first pulmonary exacerbations (PEs) was 230 days in the Linhaliq treatment group as compared to 158 days in the placebo group. For the first secondary efficacy endpoint, there was a 37% reduction in the frequency of PEs over the 48-week treatment period in the Linhaliq treatment group as compared to the placebo group.

In ORBIT-3 the median time to first PE was 214 days in the Linhaliq treatment group as compared to 136 days in the placebo group. For the first secondary efficacy endpoint, there was a 15% reduction in the frequency of PEs over the 48-week treatment period in the Linhaliq treatment group as compared to the placebo group but it was not statistically significant (p=0.2565). Neither trial demonstrated a statistically significant improvement for Linhaliq compared to placebo in the secondary endpoint, quality of life, when the difference in the Respiratory Domain score of the QoL-B questionnaire was examined between baseline and Week 48.

Both studies demonstrated a statistically significant reduction in P. aeruginosa density at Day 28, the end of the first on- treatment period. For each study, the magnitude of this antibiotic effect remained persistent throughout all on-treatment periods. Similarly, the Phase IIb trial ORBIT-2 met its primary efficacy endpoint of reduction of P. aeruginosa density at Day 28 (p=0.002). Linhaliq was generally safe and well tolerated in both Phase III studies.

Aradigm discussed the results of the Phase III studies at pre-submission meetings with EMA in October and November 2017. Based on these discussions, the statistical analysis of the results was changed from the pre-specified plan to stratification based on sex and the frequency of pulmonary exacerbations in the prior year, as the stratum for current smokers contained a small number of subjects.