FDA Rejects Linhaliq for Chronic Bronchiectasis Lung Infections

Complete response letter outlines extensive recommendations

The FDA has rejected the new drug application (NDA) for Linhaliq (Aradigm Corporation) as a treatment for non-cystic fibrosis bronchiectasis (NCFBE) patients who have chronic lung infections with Pseudomonas aeruginosa.

Aradigm said it received a complete response letter (CRL) stating that the agency cannot approve the NDA in its present form. The CRL raised concern about clinical data, a human factors validation study, and product quality. The recommendations in the CRL include:

  • An independent third party verification of the phase 3 results via analyses of source data as per the statistical analysis plan.
  • An additional phase 3 trial that demonstrates a significant treatment effect on clinically meaningful endpoints that could evaluate the coprimary 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).
  • A request to conduct another human factors study to demonstrate that the product packaging and instructions for use are effective.
  • Additional product quality information with respect to microbiology and a new in vitro drug release method development report.

"We remain confident in the efficacy, safety, and quality of Linhaliq and will request a meeting with FDA to discuss the topics covered in the CRL with the view to developing plans to move towards resubmission of the Linhaliq NDA as soon as possible,” said Igor Gonda, PhD, President and Chief Executive Officer at Aradigm. “We are committed to continue working on the approval of Linhaliq for NCFBE patients who have very severe disease with high morbidity and mortality and no available treatment options.”

The Linhaliq application was based on data from three clinical studies. Two phase 3 studies, ORBIT-3 and ORBIT-4, were identically designed, multinational, randomized, double-blind, and placebo controlled. Both were conducted concurrently in similar geographies over 48 weeks, with an additional four weeks of open-label treatment and a 30-day safety follow up. Together with the phase 2b 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.

Source: Aradigm; January 29, 2018.