The U.S. Food and Drug Administration (FDA) told Aradigm the agency could not approve the company’s New Drug Application (NDA) for Linhaliq in its present form.
Linhaliq is designed to treat patients with non-cystic fibrosis bronchiectasis who get chronic Pseudomonas aeruginosa lung infections.
Aradigm received a complete response letter (CRL) from the FDA regarding its NDA for Linhaliq. The letter stated the reasons for the FDA’s denial and offered recommendations if Aradigm wants to resubmit the application.
Among the agency’s reasons for rejecting the NDA were concerns about clinical data, product quality, and a “human factors validation study.”
Linhaliq is an experimental inhaled therapy based on the antibiotic ciprofloxacin, which is often prescribed for acute lung infections and has a broad-spectrum antibacterial activity – primarily against P. aeruginosa.
The NDA rejection likely doesn’t come as a huge surprise to Aradigm. Earlier this month, an FDA advisory committee recommended against the approval of Linhaliq as a therapy for P. aeruginosa infections in bronchiectasis.
Still, Aradigm officials said they remain committed to working with the FDA to get Linhaliq approved.
“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,” Igor Gonda, PhD, president and CEO of Aradigm, said in a press release.
In its CRL, the FDA recommends an independent third-party verification of the Phase 3 results upon which the NDA was based via analyses of source data and statistics.
The agency also wants another Phase 3 trial that demonstrates a significant treatment effect of Linhaliq on clinically meaningful endpoints over a period of two or more years.
In addition, the agency requested another Human Factors Study, which shows that the product packaging and instructions are clear and the product can be used safely and effectively.
The FDA’s CRL indicated a need for additional product quality information regarding microbiology and a new in vitro drug release method report.
“We are committed to continue working on the approval of Linhaliq for [non-cystic fibrosis bronchiectasis] patients who have very severe disease with high morbidity and mortality and no available treatment options,” Gonda said. “We thank these patients and their caregivers for participating in a decade of clinical research that brought us to this point.”
Aradigm’s NDA for Linhaliq was based on data from three clinical trials – Phase 3 ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245), and Phase 2a ORBIT-2. The first two trials were identically designed and were conducted over 48 weeks, with an additional four weeks of open-label treatment and a 30-day follow-up period.
While the two Phase 3 studies led to similar findings – Linhaliq treatment was shown to increase the time to the first pulmonary exacerbation in patients – results were statistically significant only in the ORBIT-4 trial.