March 9, 2011 — Advisors to the US Food and Drug Administration (FDA) on Tuesday backed Novartis Pharmaceuticals' new drug application for indacaterol maleate (Arcapta Neohaler) for chronic obstructive pulmonary disease (COPD), but only in the 75-μg dose, not in the 150-μg dose.
Indacaterol maleate is a long-acting β-adrenergic agonist (LABA) that is taken once daily. If approved, it would be the only once-daily bronchodilator on the US market. It is already approved in Europe for COPD.
Novartis is seeking approval of 2 doses, 75-μg and 150-μg, with the higher dose being reserved for patients with more severe bronchial obstruction. The panel struggled with the necessity of both doses, in particular the higher dose.
After a day-long session, the FDA Pulmonary-Allergy Drugs Advisory Committee voted 13 to 4 (with no abstentions) in favor that the available efficacy and safety data provide substantial evidence to support approval of indacaterol inhalation powder, 75-μg, for the long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD.
However, the panel voted 12 to 5 against approval of the 150-μg dose on the basis of available efficacy and safety data. To reach its decision, the panel reviewed data from pivotal studies of the drug conducted in more than 15,000 patients with COPD.
Those rejecting the higher dose cited a failure of data showing superior efficacy over the lower dose. There was no evidence of further bronchodilation with the higher dose in any patient subgroup, one panel member noted. Several panel members said they thought the additional efficacy did not outweigh the potential for additional safety issues.
In her presentation, Banu Karimi-Shah, MD, Medical Officer, Division of Pulmonary, Allergy and Rheumatology Products, Center for Drug Evaluation and Research, FDA, noted that trial data showed a "numerical trend" of an increasing incidence of acute respiratory-related events in patients with COPD when going from the 75-μg to the 150-μg dose. This signal, she said, "reinforces the importance of selecting the lowest possible effective dose."
However, panel member Thomas Alexander Platts-Mills, MD, PhD, from the University of Virginia Medical Center in Charlottesville, said he didn't feel that the 150-μg dose "should be judged as less safe" than the 75-μg dose.
Panel member Peter Terry, MD, from Johns Hopkins Medical Institutions, Division of Pulmonary and Critical Care Medicine, Baltimore, Maryland, said he voted "no" on the 150-μg dose because there was "no compelling evidence of a significant difference between the 75- and 150-μg doses."
Panel member Daren Knoell, PharmD, from the Ohio State University, Davis Heart and Lung Research Institute in Columbus, said he would like to see a trial specifically designed to see whether "a higher dose in more severe patients is warranted."
It was also noted that the 75-μg and 150-μg doses were never directly compared. Several panel members said they'd like to see such a head-to-head study, as well as longer-term data and data in more heterogenous populations.
During the open public comment portion of the session, John W. Walsh, a COPD patient and president of the nonprofit COPD Foundation, applauded the FDA for "accelerating approval of new therapies for COPD."
It is "unacceptable," he said, that there are only a handful of approved therapies for COPD, currently the third leading cause of death in the United States.
Walsh noted that "currently available LABAs are all given twice a day, and adherence is a great challenge. The advantage of a once-daily LABA to increase compliance and impact adherence cannot be overstated," he said.
A final decision by the FDA, which usually follows panel recommendations, is due April 1, 2011.
Medscape Medical News © 2011
Cite this: FDA Panel Backs Lower Dose of Indacaterol Maleate for COPD - Medscape - Mar 09, 2011.