The Antimicrobial Drugs Advisory Committee voted 12-3 against supporting whether Aradigm Corporation provided substantial evidence for the safety and efficacy of inhaled ciprofloxacin dispersion.
A US Food and Drug Administration (FDA) committee has voted to not recommend approval for an investigative non-cystic fibrosis bronchiectasis (NCFBE) therapy for patients with chronic lung Pseudomonas aeruginosa infections.
The Antimicrobial Drugs Advisory Committee (ADAC) voted 12-3, with 1 abstention, against supporting a posed question of whether applicant Aradigm Corporation provided substantial evidence for the safety and efficacy of inhaled ciprofloxacin dispersion (Linhaliq), in delaying the time to first exacerbation after starting treatment in NCFBE patients with the chronic lung infection.
The vote of recommendation came 2 weeks prior to the therapy’s Prescription Drug User Fee Act (PDUFA) action date of January 26. While the FDA will make its own decision to Aradigm’s application, it takes the committee’s advice into consideration.
Ciprofloxacin dispersion’s candidacy for NCFBE patients with chronic lung Pseudomonas aeruginosa infections is based on data from 3 clinical trials. The 2 phase 3 studies included in Aradigm’s application (ORBIT-3, ORBIT-4) were 48-week, multinational, randomized 2:1 double-blind trials with a placebo-controlled population. The primary endpoint in both trials was an increase in the median time to first mild, moderate or severe pulmonary exacerbation (PE).
In ORBIT-3, the median time to first mild, moderate or severe PE was 221 days in the once-daily ciprofloxacin treatment group, versus 136 days in the placebo group, a similar rate to that of ORBIT-4 (230 days versus 163 days, respectively) but not statistically significant (P = ­0.8488).
ORBIT-4 ciprofloxacin patients reported a 37% reduction in PE frequency over 48 weeks, versus placebo (P = 0.0007). In ORBIT-3, the therapy group reported a 13% reduction in 48-week PE frequency versus placebo (P = 0.3125).
Aradigm combined the efficacy results with that of a phase 2b trial (ORBIT-2) to prove ciprofloxacin’s clinical efficacy to the FDA. The therapy also showed safety and tolerability in patients during the phase 3 trials.
Ciprofloxacin is an antibiotic therapy. Its consideration for NCFBE patients with chronic lung Pseudomonas aeruginosa infections is in line with the role antibiotics currently play in treating Pseudomonas infections.
Marin Kollef, MD, Professor of Medicine and Virginia E. & Sam J. Golman Chair, Respiratory Intensive Care department, Washington University School of Medicine, told MD Magazine that combination antibiotic therapy “grew up with Pseudomonas infection” due to its difficulty to treat from both an antibiotic and virulent perspective.
“The simplest way to think of that is, by having a combination of antibiotics available, we may be able to increase the likelihood of at least 1 of them being active against the bug,” Kollef said.
Kollef added there’s a possibility that in using different antibiotic combinations, a “synergistic effect” could be found in how the treatments compliment each other in combating the infection.
Inhaled antibacterial drugs such as tobramycin, gentamicin, and aztreonam, have been studed for the prevention of exacerbations in NCFB patients, according to the ADAC, but have reported mixed clinical results. No inhaled antibacterial drugs have yet been approved for the indication.
Igor Gonda, PhD, President and Chief Executive Officer of Aradigm, expressed disappointment in the ADAC vote, but confidence in the therapy’s benefits for patients with NCFBE.
“We will work closely with the FDA to address the issues discussed by the panel today as they complete their review of Linhaliq,” Gonda said in a statement. “We are committed to helping NCFBE patients, who presently have no available treatment options.”
Related Coverage >>>