Dr. Chowdhury noted that there are no 12-week studies that include both the 75-mcg and 150-mcg doses in the same study.
Across the various studies for indacaterol, the accumulated SGRQ data showed statistical significance over placebo for all active treatments, aside from tiotropium, including the full range of indacaterol doses. In an analysis of pooled data from the COPD trials, Dr. Chowdhury pointed out that there was no statistically significant difference among the indacaterol doses in terms of the percentage of patients for whom an improvement in SGRQ score was considered clinically important. "Considering the evidence collectively, a labeling claim based on the improvement in SGRQ scores for the dose of 150 mcg seems to be questionable," he concluded.
Safety Concerns in Both Asthma and COPD
The earlier asthma studies raised safety concerns because there were two deaths in the indacaterol group in one study, and both patients were receiving concomitant inhaled corticosteroids, Dr. Chowdhury noted. Furthermore, serious adverse events related to asthma exacerbation or respiratory events appeared to be more common in indacaterol-treated patients.
A safety addendum to the clinical review written by Dr. Banu Karimi-Shah, a medical officer with the FDA’s division of pulmonary, allergy, and rheumatology products, discussed a blinded, adjudicated analysis comparing indacaterol-treated patients with controls with regard to respiratory-related death, hospitalization and intubation. The analysis was conducted by Novartis at the FDA’s request to establish whether there was a safety disadvantage with the 150-mcg dose.
Focusing on data from the COPD population, Dr. Karimi-Shah wrote: "Although the magnitude of the signal is not large, there does appear to be a numerical trend of increasing incidence of acute respiratory-related events, particularly those that were adjudicated as having been COPD-related, as the dose of indacaterol rises from 75 mcg to 300 mcg.