A U.S. Food and Drug Administration (FDA) advisory panel voted not to recommend ciprofloxacin dry powder for inhalation (Cipro DPI), being developed by Bayer, to be approved for the treatment of non-cystic fibrosis bronchiectasis.
Reasons given for this decision were a lack of data consistency regarding safety and efficacy in pivotal clinical trials of the potential therapy, and failure to meet all but one of the trials’ primary goals.
A majority of the FDA’s Antimicrobial Drugs Advisory Committee (AMDAC) opposed both Cipro DPI treatment courses evaluated in two Phase 3 clinical trials — the 14-day and 28-day regimens used in RESPIRE 1 (NCT01764841) and RESPIRE 2 (NCT02106832).
Members recommended against the 14-day Cipro DPI course by a margin of 9–6, but opposed the 28-day course in a 14–1 vote.
That 14-days-on, 14-days-off treatment regiment was also the only one to meet a primary trial endpoint with significance — that of increased time to a pulmonary exacerbation or flare — and only in the RESPIRE 1 study.
The two trials were of similar design — evaluating a 14-day and 28-day treatment courses — but differed slightly in their analyses according to agreements set with the FDA, the European Medicines Agency (EMA) and other agencies. Both assessed ciprofloxacin DPI as a long-term, intermittent therapy, and both ran for 48 weeks.
The FDA can choose not to accept this recommendation by the advisory panel when it votes on the company’s application, but it usually does.
In a statement to Bronchiectasis News Today, Bayer said that it is continuing discussions with the agency before the expected final decision.
“Bayer is working closely with the FDA and we anticipate a decision by the end of 2017,” the statement read.
Regarding Cipro DPI’s safety profile, a briefing document given by the panel noted no unusual side effects linked to the treatment, which included headache, bronchospasm, dyspnea or shortness of breath, and cough.
But mention was made of concerns with bacterial resistance to ciprofloxacin, which was “noted over the course of the Phase 3 trials.” This resistance is particularly worrisome for infections with the aggressive and difficult-to-treat Pseudomonas aeruginosa bacteria.
Data showed a marked increase in ciprofloxacin-resistant P. aeruginosa in treated patients in both RESPIRE studies compared to those given placebo.
Ciprofloxacin DPI is an investigational drug-device combination intended to reduce exacerbations in non-CF bronchiectasis patients with bacterial pathogens in their respiratory tract. It consists of the antibiotic ciprofloxacin delivered to the lung using a powder solution inhaled from a handheld device developed by Novartis, the T-326 inhaler.
In people with bronchiectasis, sputum (saliva and mucus) pools in the small airways form a fertile ground for bacterial growth that often results in chronic airway infections.
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