SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on March 8 recommended that the inhaled bronchodilator indacaterol should be approved for patients with chronic obstructive pulmonary disease.
The FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 13-4 that the data on the safety and efficacy of the 75-mcg dose of indacaterol, as a maintenance treatment, provided substantial evidence to support the drug’s approval at this dose, for the proposed indication: the long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Indacaterol, a long-acting beta-2 adrenergic agonist (LABA) that is administered in a dry-powder inhaler, has a rapid onset of effect sustained over 24 hours, according to Novartis, which filed for approval of two once-daily doses: 75 mcg and 150 mcg. But in a 12-5 vote, the panel recommended against approval of the higher dose, largely because of the paucity of data directly comparing the two doses and, as the panel chair said, "No compelling difference" in efficacy that was evident between the two doses.
The 150-mcg once-daily dose and a higher dose (300 mcg once daily) of indacaterol were approved to treat COPD in the European Union in September 2009, where it is marketed as the Onbrez Breezhaler; the drug at those doses is now approved in more than 50 countries.
Initially, Novartis had applied for approval of these two doses in December 2008, but the FDA requested that the company study lower doses of the drug, after the agency review concluded that no clinically meaningful advantage had been shown for the 300-mcg dose over the 150-mcg dose and because of safety concerns. There were more cardiovascular and cerebrovascular adverse events among patients with COPD treated with indacaterol, when compared with those on placebo and the active compactor, formoterol; and in studies of indacaterol in patients with asthma, there were some deaths, possibly related to indacaterol. In addition, treatment with inhaled LABAs has been linked to severe asthma exacerbations and asthma-related deaths in patients with asthma.
At the meeting, Novartis presented the results of five phase III studies of the 75-mcg, 150-mcg, and 300-mcg doses, compared with placebo or active controls in approximately 4,000 patients with COPD. After 12 weeks, there were significant improvements in lung function associated with each dose, when compared with placebo. In the safety database of patients with COPD, the risk of serious cardiovascular events (including MI, stroke, or cardiac death) was not increased, and there was no increase in acute respiratory events associated with any dose of indacaterol studied, according to Novartis.
If both doses were approved, indacaterol would be the first bronchodilator in the United States to be approved at two doses for the treatment of COPD; only one dose of formoterol and salmeterol, which are also LABAs, are approved for COPD treatment
Pending approval, Novartis plans to market indacaterol in the United States as the Arcapta Neohaler.
The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.