The FDA’s Antimicrobial Drugs Advisory Committee (AMDAC) convened on November 16th to discuss ciprofloxacin inhalation powder (NDA 209367), sponsored by Bayer HealthCare Pharmaceuticals, Inc., for the proposed indication of reduction of exacerbations in non-cystic fibrosis (CF) bronchiectasis (NCFB) in adult patients (≥18 years of age) with respiratory bacterial pathogen.
Ciprofloxacin is a synthetic, fluorinated carboxyquinolone and has in vitro activity against both Gram-negative and Gram-positive organisms. The bactericidal action of ciprofloxacin results from inhibition of bacterial type II topoisomerases (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
The committee was asked whether the applicant provided substantial evidence of the safety and effectiveness for the ciprofloxacin dry powder inhaler (DPI) 14 and 28- day regimens in delaying the time to first exacerbation after starting treatment. At the end of the meeting, the committee voted Yes: 6 / No: 9 and Yes: 1 / No: 14 to the questions as to whether the sponsor provided substantial evidence of the safety or effectiveness of 14- and 28-day ciprofloxacin regimens, respectively, in delaying the time to first pulmonary exacerbation after starting treatment.
The committee’s negative vote came after review of data from the Phase III RESPIRE 1 and RESPIRE 2 trials with a total of 937 patients with non-CF bronchiectasis. In RESPIRE 1, the 14-day on/off regimen of ciprofloxacin met the primary endpoint of improving median time to first pulmonary exacerbation vs. pooled placebo (>336 vs. 186 days, p=0.0005), but the 28-day on/off regimen did not. In RESPIRE 2, both the 14- and 28-day on/off regimens of ciprofloxacin missed the primary endpoint of improving median time to first pulmonary exacerbation vs. pooled placebo.
FDA advisory committees are panels of independent experts who advise the FDA on specific questions raised by the FDA as they consider regulatory decisions. Although not bound by the recommendation of the committee, the Agency usually follows its guidance during the final review process. Ciprofloxacin inhalation powder is a qualified infections disease product and has been granted orphan drug status, fast track status, and breakthrough therapy designation for the treatment of NCFB.
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