Aradigm’s attempt to commercialize an inhalable version of a generic antibiotic as a treatment for chronic lung infections has stalled with the FDA’s rejection of the company’s drug approval application.
Hayward, CA-based Aradigm (NASDAQ: ARDM) says it would be required to conduct another Phase 3 study of its version of ciprofloxacin (Linhaliq) in order to resubmit the application. The FDA’s rejection comes three weeks after an advisory committee to the regulator voted against recommending approval for the Aradigm drug.
Shares of Aradigm fell nearly 25 percent to $1.68 apiece following the announcement of the news on Monday.
Aradigm has spent the last decade researching and developing drug delivery technologies, particularly respiratory technologies. The company’s inhalable form of ciprofloxacin is its lead drug. Aradigm was seeking FDA approval of the drug as a treatment for bronchiechtasis, a condition in which the bronchial tubes become thickened and inflamed from infection.
The Aradigm drug was developed for non-cystic fibrosis patients whose infections are attributed to Pseudomonas aeruginosa (P. aeruginosa). The company says its inhaled ciprofloxacin would provide an option for a condition that has no treatment and can become fatal.
Aradigm has been testing its inhalable ciprofloxacin in partnership with Grifols (NASDAQ: GRFS). Under a 2013 agreement, Grifols obtained worldwide rights to drug. In exchange, the Spain-based company committed $65 million toward clinical studies. Aradigm stands to gain up to $20 million pegged to milestones, such as FDA approval.
The Aradigm drug was tested in two placebo-controlled Phase 3 studies enrolling a total of 582 patients. The main goal of the studies was evaluating the time from the start of the trial to the first pulmonary exacerbations—worsening of cough, congestion, and other symptoms. The secondary goal of the studies was measuring the frequency of those symptoms. Each study evaluated patients over 48 weeks.
In Phase 3 results released by the company, the Aradigm drug beat a placebo. The treatment group showed an increase in the median time to pulmonary exacerbations, as well as a statistically significant reduction in the frequency of these symptoms. But FDA reviewers had concerns about the trial design. According to documents prepared for the advisory committee hearing, the reviewers said that the study’s measure of the time to the first pulmonary exacerbation ignores subsequent exacerabations and is therefore “not a characterization of disease-related events.” Also, the reviewers said the secondary goal of measuring the frequency of exacerbations does not account for their duration. They added that 48 weeks might not be enough time to assess a drug meant to treat a chronic disease.
According to Aradigm, the FDA rejection letter recommended an independent third-party verification of the clinical trial results, as well as an additional Phase 3 study. That study, the FDA said, could measure both the frequency and severity of the symptoms as the main study goals, and assess the drug’s efficacy over the course of two years or more. The FDA letter also asked the company to conduct a human factors study evaluating the product’s packaging instructions. And last, the FDA sought more information about the quality of Aradigm’s drug product.
In a prepared statement, Aradigm CEO Igor Gonda said that the company will ask for a meeting with the FDA to discuss a resubmission of the drug application. In the near term, he said Aradigm is focused on its application for approval of the drug in Europe.
Image by Flickr user University of Liverpool Faculty of Health & Life Sciences via a Creative Commons license.