An advisory committee is recommending against U.S. regulatory approval of a mist formulation that Aradigm developed to deliver an antibiotic for the Pseudomonas aeruginosa lung infections in bronchiectasis.
Although the U.S. Food and Drug Administration can reject the recommendation against Linhaliq, an inhaled form of ciprofloxacin, it will consider the advisers’ views in its decision. The treatment is for bronchiectasis that is not associated with cystic fibrosis.
The FDA decision is expected no later than Jan. 26.
“While we are disappointed with the outcome of the ADAC [Antimicrobial Drugs Advisory Committee] vote, we remain confident in the efficacy, safety and tolerability of Linhaliq in NCFBE [non-cystic fibrosis bronchiectasis] patients,” Igor Gonda, the president and CEO of Aradigm, said in a press release.
The recommendation against Linhaliq’s approval is a setback in the treatment’s development. In September of last year, the FDA agreed to speedily review Aradigm’s application for approval, submitted in July 2017, after two meetings between the company and regulators.
In addition, the medication, previously known as Pulmaquin, has been awarded Qualified Infectious Disease Product (QIDP) designation, orphan drug status, and fast-track status. All signaled that the agency believed the treatment was a step forward in the management of chronic lung infections in bronchiectasis.
Twelve members of the advisory committee, which focuses on antimicrobial medications, voted no to the question: “Has the applicant provided substantial evidence of the safety and efficacy of ciprofloxacin dispersion for inhalation in delaying the time to first exacerbation after starting treatment in non-cystic fibrosis bronchiectasis patients with chronic lung infections with Pseudomonas aeruginosa?”
Three voted in favor of Linhaliq, and one opted not to vote.
The two Phase 3 studies looked at the time it took for patients to develop a first lung disease exacerbation on Linhaliq, compared with a placebo. This was the studies’ primary outcome measure, but they also explored rates of lung exacerbations and severe lung exacerbations over 48 weeks.
While the two Phase 3 trials had similar outcomes — a median increase of 72 and 78 days to the first pulmonary exacerbation with Linhaliq treatment — results were statistically significant in only one of the trials.
Reductions in exacerbation rates differed among the trials. In ORBIT-4, researchers noted a 37 percent reduction in exacerbation rates, which was significant. The 15 percent reduction in ORBIT-3 was not. Similarly, severe exacerbations were reduced by 60 percent in ORBIT-4 and 20 percent in ORBIT-3.
This meant that the ORBIT-4 trial met its objectives, while ORBIT-3 did not.
“We will work closely with the FDA to address the issues discussed by the panel today as they complete their review of Linhaliq. We are committed to helping NCFBE patients, who presently have no available treatment options,” Gonda said.