FDA Panel Votes in Favor of Olodaterol for COPD

Miriam E. Tucker

January 30, 2013

A federal advisory panel has voted 15 to 1 with 1 abstention to recommend approval of olodaterol, a new medication for treating patients with chronic obstructive pulmonary disease.

The Pulmonary-Allergy Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted 15 to 1 with 1 abstention in 3 separate votes that the data support the efficacy, safety, and approval of Boehringer Ingelheim's olodaterol, a long-acting beta-agonist, delivered via a metered dose inhaler under the proposed trade name Striverdi Respimat.

The proposed indication is for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. The proposed dose is two 2.5-μg sprays once daily for a total dose of 5 μg olodaterol.

Panel member James M. Tracy, DO, voted yes for efficacy, safety, and approval. Dr. Tracy, assistant professor of internal medicine at Creighton University School of Medicine, Omaha, Nebraska, listed his reasons: "Background medications, spectrum of disease severity, real-world setting, all the endpoints were met."

Exercise Tolerance

The company is also seeking FDA approval to make claims in the product label about olodaterol's ability to increase exercise tolerance, increase inspiratory capacity at rest and during exercise, and reduce lung hyperinflation based on decreased functional residual capacity. No COPD treatment currently on the US market makes such claims on their product label.

The committee did not vote on the labeling proposal but did discuss it at length. Some panel members agreed with the FDA analysis that despite a statistically significant 14% improvement in exercise tolerance, as measured in seconds, it was not clear to what degree that difference translated to clinically relevant improvement for patients.

The manufacturer's data came from 7 dose ranging/dose regimen trials (3 in COPD and 4 in asthma), four 48-week trials, and six 6-week trials, 2 of which were focused on exercise. The majority of the trials permitted patients to continue taking usual care background medications, including long-acting antimuscarinic agents (tiotropium), but not other long-acting beta-agonists.

Overall, the studies included 4936 patients with COPD (1095 patients in phase 1 and phase 2 and 3841 patients in phase 3), 731 patients with asthma, and 276 healthy volunteers. A total of 876 patients received olodaterol at the proposed marketed dose of 5 μg every day, and an additional 883 patients received olodaterol at the higher dose of 10 μg every day during the 48-week pivotal studies.

In contrast to data submitted to FDA for previous bronchodilator treatments, the phase 3 studies for olodaterol included patients with all levels of COPD severity including approximately 10% with very severe disease (Global Obstructive Lung Disease stage IV). Also included were patients with comorbidities, including hypertension in about a third of patients in the phase 3 studies.

The overall treatment effect at 12 weeks for the 5-μg dose was an average 65-mL improvement in trough forced expiratory volume at 1 second and a mean 155-mL improvement in forced expiratory volume at 1 second area under the curve. No additional benefit was seen with the 10-μg dose over the 5-μg dose.

There was a safety signal for neoplasms, with 3 patients (0.3%) in the 10-μg olodaterol group developing small cell lung cancers compared with no patients in the placebo group. Panel members agreed with company officials that the difference may be a result of chance and/or an imbalance in preexisting neoplasms between the 2 groups but urged the FDA to monitor for neoplasms specifically in postmarketing surveillance.

FDA advisory panel members are vetted for conflicts of interest and waivers are granted if necessary. No waivers were granted for this meeting.