Aradigm Corporation has submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Linhaliq for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) due to Pseudomonas aeruginosa
Linhaliq, previously known as Pulmaquin, is a slow release formulation of the antibiotic ciprofloxacin, with a slow-release formulation of liposomal dissolved in an aqueous solution.
Bronchiectasis is a widening and scarring of the lung airways, often due to infections. Changes in the airways leads to a mucus buildup, that in turn, leads to more infections and more widening and scaring. This vicious cycle can lead to permanent damage to the lungs. It is estimated to afflict 150,000 Americans with no approved treatment.
The NDA included data from 2 Phase 3 clinical trials (ORBIT-4 and ORBIT-3), a Phase 2b study (ORBIT-2), as well as other supporting evidence. The FDA has 60 days to determine whether the NDA is complete and acceptable for filing.
In previous meetings with the FDA, Aradigm discussed the clinical evidence supporting the use of Linhaliq in NCFBE. Based on those discussions, the statistical analysis of the results was modified.
Using the new statistical analysis, the Phase 3 ORBIT-4 study showed that NCFBE patients given Lunhaliq had a median time to first pulmonary exacerbations of 230 days compared to 158 days in the placebo group (P
= .0323). Further, there was a 37% reduction in the frequency of pulmonary exacerbations in the Linhaliq group as compared to the placebo group over the 48-week study (P
= .0006) and a 60% reduction in the frequency of severe pulmonary exacerbations in the Linhaliq group compared to placebo (P
In the Phase 3 ORBIT-3 study, the median time to first pulmonary exacerbations was 214 days in the Linhaliq group vs 136 days in the placebo group; that difference was not statistically significant.
Linhaliq was generally safe and well-tolerated in both Phase 3 studies. There were no significant differences in the changes of lung function (FEV1 % predicted and FVC % predicted) or symptoms of airway irritation between the Linhaliq and placebo groups in the two studies.
89% of patients who completed ORBIT-3 and 91% of patients who completed ORBIT-4 enrolled in the studies’ open label extension studies.
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