FDA provides complete response to application for Linhaliq in bronchiectasis.

Aradigm Corporation received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) for Linhaliq (inhaled ciprofloxacin) as a treatment for non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic lung infections with Pseudomonas aeruginosa (P. aeruginosa). The CRL states that the FDA has determined that it cannot approve the NDA in its present form and provides specific reasons for this action along with recommendations needed for resubmission; the areas of concern include clinical data, human factors validation study and product quality.

The recommendations in the CRL include an independent third party verification of the Phase III results via analyses of source data as per the statistical analysis plan and an additional Phase III clinical trial that demonstrates a significant treatment effect on clinically meaningful endpoints which could evaluate the co-primary endpoints of frequency and severity of exacerbations to assess for durable evidence of efficacy over a period of two years (or more, if scientifically justified). The CRL also included a request to conduct another Human Factors Study to demonstrate that the product packaging and instructions for use are effective, and the CRL requested, among other things, additional product quality information with respect to microbiology and a new in vitro drug release method development report.

The Linhaliq application was based on data from three clinical studies. Two Phase III studies, ORBIT-3 and ORBIT-4, were identically designed, multinational, randomized (2:1), double-blind and placebo controlled. Both were conducted concurrently in similar geographies over 48 weeks, with an additional 4 weeks of open-label treatment and a 30-day safety follow up. Together with the Phase IIb ORBIT-2 study, these trials were part of the NDA submission to provide evidence of the clinical benefit of Linhaliq for patients with NCFBE who have chronic lung infections with P. aeruginosa.