FDA Rejects Linhaliq NDA

Earlier this month, Aradigm Corporation sat down with the U.S. Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee, and this morning, the company announced that it received a Complete Response Letter (CRL), denying its New Drug Application (NDA) for Linhaliq.

Linhaliq, previously known as Pulmaquin, is intended to serve as a potential therapy for non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic lung infections with pseudomonas aeruginosa (P. aeruginosa). It is an inhalation formulation of unencapsulated ciprofloxacin, with a slow-release formulation of liposomal dissolved in an aqueous solution. The NDA’s submission was based on data from a Phase 2b study (ORBIT-2) and a pair of Phase 3 clinical trials (ORBIT-3, ORBIT-4).

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 necessary for resubmission.

The FDA’s areas of concern include clinical data, human factors validation study and product quality. Recommendations for resubmission include an independent third party verification of the Phase 3 results via analyses of source data as per the statistical analysis plan and a supplementary Phase 3 clinical trial that exhibits a noteworthy 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 2 years (or more, if scientifically justified).

"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, Ph.D., president and chief executive officer at Aradigm in a press release. “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. We thank these patients and their care givers for participating in a decade of clinical research that brought us to this point. Our focus is also on the submission in the near future for marketing approval in the European Union.”

In the CRL, the FDA requested Aradigm to conduct another Human Factors Study and more product quality information.

Linhaliq, if approved, would be the first regulated therapy for P. aeruginosa, and is an inhalation formulation of unencapsulated ciprofloxacin, with a slow-release formulation of liposomal dissolved in an aqueous solution. Infections are typically the cause of bronchiectasis, which is characterized by a widening and scarring of the airways in the lungs. The alterations to the airways can result in mucus buildups which, in turn, lead to recurrent infections and an increase in inflammation.

The condition can cause permanent bronchial wall damage, and is estimated to affect 150,000 Americans.

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