The Food and Drug Administration (FDA) has approved Bronchitol® (mannitol; Chiesi USA) inhalation powder as add-on maintenance therapy to improve pulmonary function in patients aged 18 years and older with cystic fibrosis (CF). Bronchitol is only indicated for use in adults who have passed the Bronchitol Tolerance Test (BTT), which identifies patients who are hyperresponsive to Bronchitol through a series of monitored inhalations of increasing doses.

The approval was based on efficacy and safety data from 3 randomized, double-blind, controlled phase 3 trials in patients with CF. Trial 1 included 423 patients aged 18 years and older with a baseline predicted FEV1 greater than 40% and less than 90%; Trial 2 included 295 patients aged 6 years and older with predicted FEV1 greater than or equal to 30% and less than 90%; and Trial 3 included 305 patients aged 6 years and older with predicted FEV1 greater than or equal to 40% and less than 90%. 

Patients were randomized to receive Bronchitol 400mg by oral inhalation or control twice daily; each dose of Bronchitol was preceded by use of an inhaled short-acting bronchodilator (albuterol or equivalent). The primary efficacy end point for all 3 trials was improvement in lung function as determined by the mean change from baseline in pre-dose FEV1 (mL) over 26 weeks.

Results from Trial 1 showed that treatment with Bronchitol was associated with a statistically significant improvement in FEV1 vs control (adjusted mean difference: 51mL [95% CI: 6, 97]; P =.028). In Trials 2 and 3, the adjusted mean differences in FEV1 between Bronchitol and control were 68mL (95% CI: 24, 113) and 52mL (95% CI: 3, 107), respectively, in the intention-to-treat population. Moreover, post-hoc descriptive analyses of the adult subgroups in Trials 2 (n=209) and 3 (n=157) showed adjusted mean differences in FEV1 of 78mL (95% CI: 21, 135) and 78mL (95% CI: 2, 153), respectively.

With regard to safety, the most common adverse reactions associated with therapy included cough, hemoptysis, oropharyngeal pain, vomiting, bacteria in sputum, pyrexia, and arthralgia. Bronchitol is contraindicated for use in patients who have failed to pass the BTT.

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“Bronchitol offers a portable and discreet option for CF management, with no routine cleaning or maintenance of the inhaler device required,” said Dr. Carmen Dell’Anna, Head, Global Medical Excellence at Chiesi. “We are excited to achieve its approval in the US for adults living with cystic fibrosis.”

Bronchitol is supplied as 40mg of mannitol per capsule in 10-, 140-, and 560-count cartons with inhalers and is expected to be available in March 2021.

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  1. Chiesi USA, Inc. announces FDA approval of Bronchitol® (mannitol) inhalation powder. [press release]. Cary, NC: Chiesi USA, Inc; November 2, 2020. 
  2. Bronchitol [package insert]. Cary, NC: Chiesi USA, Inc; 2020.