Brovana Inhalation Solution Study Data Presented at American College of Chest Physicians Annual Conference
The Effect of Twice-Daily Nebulized Arformoterol on QTC in Subjects With COPD
This four-week, placebo-controlled, randomized, double-blind, multicenter, parallel-group, dose-ranging study evaluated changes in QTc interval in patients with chronic obstructive pulmonary disease (COPD) who were administered arformoterol at various doses, or placebo. Patients were divided into Part A (n=215) and were administered arformoterol 5 mcg, 15 mcg, or 25 mcg or placebo twice daily for two weeks, and subsequently re-randomized in Part B (n=191) and administered arformoterol 15 mcg, 25 mcg, or 50 mcg or placebo once daily for two weeks. Two models were used to calculate QTc from results of electrocardiograms (ECGs) for each of the patients in the study. Based on the data analyzed in this study, dosing with arformoterol did not prolong cardiac repolarization.
An Open-Label Study of Arformoterol Inhalation Solution and Racemic Formoterol Dry-Powder Inhaler in Subjects With COPD
This Phase II, open-label, randomized, multicenter, multiple-dose, 3-way crossover study (n=39) evaluating BROVANA 15 mcg, and formoterol 12 mcg and formoterol 24 mcg, both administered by dry-powder inhaler (DPI), was designed to assess systemic exposure to the single isomer, (R,R)-formoterol, in each medication, and airway function efficacy for each of the treatment arms in patients with COPD. (R,R)-Formoterol is the single isomer that is responsible for bronchodilation in racemic formoterol, which is a mixture of (R,R)- and (S,S)-isomers. All treatment groups demonstrated similar improvements in airway function as measured by changes in FEV1 (forced expiratory volume in one second; a test of lung function) from predose and over the 12-hour dosing periods, on the first and last days of each treatment sequence. However, in this study, mean steady state concentrations of (R,R)-formoterol were similar for the BROVANA 15 mcg and formoterol 12 mcg groups, and higher concentrations of (R,R)-formoterol were observed in the formoterol 24 mcg group. All treatments were well tolerated and adverse events were similar for all groups.
Baseline BODE (Body mass index, Obstruction, Dyspnea and Exercise capacity) Correlates With Baseline Dyspnea Index (BDI) and Baseline St. George's Hospital Respiratory Questionnaire (SGRQ), But Not With Changes in These Measures Following LABA (long-acting beta-agonist) Treatment in Two 12-Week Double-Blind Trials
BODE is an index that incorporates assessments of COPD symptoms, pulmonary function, nutritional status and exercise capacity and is believed to be a better indicator than FEV1 alone in predicting death and hospitalization in patients with COPD. This post-hoc analysis of a double-blind, double-dummy, randomized, placebo- and active-controlled, multicenter, parallel-group study assessed the relationship between pre-treatment BODE level and two other patient-based COPD severity measures, as well as whether change in these measures was related to pre-treatment BODE scores in patients administered either BROVANA or salmeterol. The analysis showed that baseline BODE scores had a moderate correlation with BDI and baseline SGRQ scores. A one-unit increase in the severity of COPD measured by BODE was associated with a 3.7-unit increase in the SGRQ and a 0.46-unit worsening of dyspnea on the BDI scale. The changes observed in dyspnea and SGRQ scores after administration of placebo, salmeterol or BROVANA were not associated with baseline BODE score. These results support the BODE index as a useful instrument to assess COPD severity, but suggest that the index is insensitive in predicting patients who will have improvements in two other COPD severity scales when given inhaled long-acting bronchodilator therapy.
The Influence of Breathing Pattern During Nebulization on the Emitted Dose of Arformoterol
This study assessed whether various simulated breathing patterns would affect the amount of BROVANA that a patient would inhale when using a PARI LC(R) PLUS nebulizer to deliver the medication. Overall, there appeared to be no substantial difference in the amount of delivered medication for any of the simulated breathing patterns in this study. However, less residual medication was recovered from the nebulizer with longer inspiratory duration. These results suggest that the breathing pattern used during nebulization does not have a major influence on the amount of medication delivered. However, like all other nebulized treatments, the amount delivered to the lungs will depend upon patient factors, the nebulizer used and compressor performance.
"Use of long-acting bronchodilators is central to the long-term, maintenance treatment of bronchoconstriction in patients with COPD. Prior to the launch of BROVANA, patients with COPD who use medications delivered by nebulizer had to depend on more frequent dosing with short-acting beta-agonists to manage their symptoms," said Mark Corrigan, Executive Vice President of Research and Development at Sepracor Inc. "The use of BROVANA as a long-term, maintenance therapy is consistent with GOLD guidelines(1) for patients with moderate, severe or very severe COPD. We believe that BROVANA is an important therapeutic option for these patients, who comprise approximately 70 percent of those diagnosed with COPD in the U.S."(2)
BROVANA is a long-term, twice-daily (morning and evening), maintenance treatment of bronchoconstriction in patients with COPD, including chronic bronchitis and emphysema. BROVANA is for use by nebulization only.
According to the National Center for Health Statistics, COPD is the fourth leading cause of death in the U.S. and it is estimated to be the third leading cause by the year 2020. Approximately 12 million adults in the U.S. are reported to have COPD, although approximately 24 million adults have evidence of impaired lung function, which may indicate that COPD is under-diagnosed, according to the National Heart, Lung, and Blood Institute. COPD is a slowly progressive disease of the airways that is characterized by a gradual loss of lung function and includes chronic bronchitis, chronic obstructive bronchitis and emphysema, or combinations of these conditions.
BROVANA has not been demonstrated to have an impact on the progression of disease or the survival of patients with COPD.
Important Safety Information
Long-acting beta2-adrenergic agonists may increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to arformoterol (a long-acting beta2-adrenergic agonist), the active ingredient in BROVANA.
Data are not available to determine whether the rate of death in patients with COPD is increased by long-acting beta2-adrenergic agonists. BROVANA is indicated for the long-term, twice-daily (morning and evening) maintenance treatment of bronchoconstriction in COPD, including chronic bronchitis and emphysema. BROVANA is for use by nebulization only. BROVANA is not indicated for the treatment of acute episodes of bronchospasm, i.e. rescue therapy. BROVANA should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition.
BROVANA should not be used in conjunction with other inhaled, long-acting beta2-agonists. BROVANA should not be used with other medications containing long-acting beta2-agonists. As with other inhaled beta2-agonists, BROVANA can produce paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs, BROVANA should be discontinued immediately and alternative therapy instituted. BROVANA, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of BROVANA at the recommended dose, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTC interval and ST segment depression. The clinical significance of these findings is unknown. BROVANA, as with other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias and hypertension; in patients with convulsive disorders or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines.
In clinical studies, the numbers and percent of patients who reported adverse events were comparable in the BROVANA 15 mcg twice daily and placebo groups. The most frequent adverse events reported in patients taking BROVANA were pain (8%), chest pain (7%), back pain (6%), diarrhea (6%) and sinusitis (5%). BROVANA, as with other long-acting beta2-adrenergic agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTC interval because these agents may potentiate the action of adrenergic agonists on the cardiovascular system.
Please visit the BROVANA web site at www.brovana.com for complete prescribing information.
Sepracor Inc. is a research-based pharmaceutical company dedicated to treating and preventing human disease by discovering, developing and commercializing innovative pharmaceutical products that are directed toward serving unmet medical needs. Sepracor's drug development program has yielded a portfolio of pharmaceutical products and candidates with a focus on respiratory and central nervous system disorders. Sepracor's corporate headquarters are located in Marlborough, Massachusetts.
Forward Looking Statement
This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to safety, efficacy and potential benefits of BROVANA. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: Sepracor's ability to fund further clinical trials and the results of such clinical trials; Sepracor's ability to successfully commercialize BROVANA; continued growth of the COPD market; the scope of Sepracor's trademarks and patents and the success of challenges by others of Sepracor's patents and trademarks; Sepracor's ability to attract and retain qualified sales personnel and other employees; and certain other factors that may affect future operating results and are detailed in Sepracor's Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 and other periodic filings that Sepracor has made with the Securities and Exchange Commission.
In addition, the statements in this press release represent Sepracor's expectations and beliefs as of the date of this press release. Sepracor anticipates that subsequent events and developments may cause these expectations and beliefs to change. However, while Sepracor may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Sepracor's expectations or beliefs as of any date subsequent to the date of this press release.
(1) The Global Initiative for Chronic Obstructive Lung Disease 2006.
(2) Percentages from Datamonitor DMHC2147, 2005. In: Pipeline Insight: Asthma/COPD. Reference code: DMHC2251. November 2006.
Brovana is a trademark of Sepracor Inc. PARI LC is a registered trademark of PARI Respiratory Equipment, Inc. For a copy of this release or any recent release, visit Sepracor's web site at www.sepracor.com.
David P. Southwell, 508-481-6700
Chief Financial Officer
Jonae R. Barnes, 508-481-6700
Sr. Vice President
Posted: October 2007