Safety of nebulized Formoterol in COPD

Data from two Phase III clinical trials were presented today in Chicago at CHEST 2007, the annual scientific assembly of the American College of Chest Physicians (ACCP), supporting the use of Perforomist (formoterol fumarate) Inhalation Solution as a safe and effective maintenance treatment for COPD patients.

The results of both studies were included as part of the New Drug Application (NDA) filing to the U.S. Food and Drug Administration (FDA) for Perforomist™ Inhalation Solution. Perforomist™ Inhalation Solution is indicated for long-term, twice-daily maintenance treatment of bronchoconstriction for emphysema and chronic bronchitis, also known as Chronic Obstructive Pulmonary Disease (COPD).

Formoterol fumarate is a rapid and long-acting beta2-agonist (LABA) that has been previously available in the U.S. in a dry powder formulation and has twenty years of worldwide experience. Perforomist Inhalation Solution is the first and only FDA-approved nebulized form of this molecule. Nebulizers convert liquid medication into a mist that patients inhale through a mouthpiece or face mask.

The first of the two safety studies presented, “Long-Term Safety of Nebulized Formoterol in COPD: An Open-Label Active-Control Extension Study,” involved 569 COPD patients and found that twice-daily delivery of nebulized formoterol fumarate was well tolerated over a 12-month treatment period in patients with moderate-to-severe COPD. Over the course of a year, patients in the study received either 20 mcg nebulized formoterol fumarate inhalation solution (FFIS) or 12 mcg formoterol fumarate delivered by dry powder inhaler (FA) DPI.

“The study's findings indicate that nebulized delivery of formoterol fumarate is a safe long-term treatment option for patients with moderate-to-severe COPD who may prefer or require nebulization,” said James F. Donohue, MD, Chief of Pulmonary Medicine at the University of North Carolina at Chapel Hill and the lead trial investigator. “The incidences of adverse events as well as medication discontinuation due to adverse events were similar between the nebulized FFIS and dry powder FA groups. Physicians should feel confident offering Perforomist™ Inhalation Solution as an additional therapeutic choice for COPD patients with moderate-to-severe disease.”

The study also demonstrated similar electrocardiogram (ECG) results between the groups and no clinically important changes from baseline in laboratory tests, including serum potassium and glucose, vital signs, and physical examinations.

The second NDA safety study, “Cardiovascular Safety of Nebulized Formoterol in COPD Patients: A Double-Blind, Placebo-Controlled Study,” involved 351 COPD patients and described results of extensive cardiac safety monitoring as a part of a pivotal Phase IIII and efficacy trial. Twice-daily treatment with FFIS over a 12-week period was not associated with an increased incidence of cardiovascular events. Patients participating in the study were randomized into three groups to receive 20 mcg FFIS by nebulization, 12 mcg FA DPI, or placebo, each given twice daily. Cardiac safety was assessed with Holter monitoring, 12-lead ECGs, serum potassium levels, cardiac adverse events, vital signs and physical examinations.

“Often, patients with moderate-to-severe COPD have multiple serious co-morbidities, and there has been concern about the cardiovascular safety of beta2-agonists as treatment for respiratory conditions,” noted Harold S. Nelson, MD, Professor of Medicine, National Jewish Medical and Research Center and a clinical investigator. “Our research shows that Perforomist™ Inhalation Solution has a cardiac safety profile that allows its use in COPD patients. It provides another therapy choice for patients who may prefer or require twice-daily dosing by nebulizer.”

Sammy C. Campbell, MD, Professor Emeritus, University of Arizona College of Medicine, was a researcher in the FFIS long-term safety study and also had previously studied cardiovascular safety of formoterol fumarate in its dry powder formulation. “Formoterol fumarate has been shown for decades to be a safe and effective treatment for COPD,” said Dr. Campbell. “My own earlier research on the cardiovascular safety of the molecule is consistent with the research findings in today's presentation, and together they complement the positive long-term safety data. The weight of these data clearly underscore the clinical value that formoterol fumarate brings to COPD patients. Perforomist Inhalation Solution will be a welcome addition to the physician's arsenal in the battle to manage symptoms of moderate to severe COPD.”

“Dey, L.P. specializes in bringing innovative new medications to market for complex respiratory diseases,” noted Christy Taylor, Chief Operating Officer of Dey, L.P. “For more than a decade we have been the U.S. leader in sales of nebulized respiratory medications, and Perforomist Inhalation Solution, launched earlier this month, is the newest addition to this portfolio. We thank Drs. Donohue, Nelson, and Campbell for their contributions to the trials that were presented today. Their research highlights the clinical value of Perforomist™ Inhalation Solution, the first nebulized version of formoterol fumarate, for patients with moderate to very severe COPD.”

For those attending CHEST 2007, the two presentations are available as follows:

Poster viewing: Session ID 902 - COPD Treatment II
Wednesday, October 24, 2007, 12:30 – 2:00 PM
Convention Center, Exhibit Hall, McCormick Place, Lakeside Center, Chicago.

Poster # 238: Cardiovascular Safety of Nebulized Formoterol in COPD Patients: A Double-Blind, Placebo-Controlled Study

Poster # 239: Long-term Safety of Nebulized Formoterol in COPD: An Open-Label Active-Controlled Extension Study

Please note that clinical investigators will be available on-site to discuss the research findings.