FDA Approves Merck's DULERA(R) (mometasone furoate and formoterol fumarate dihydrate) Inhalation Aerosol for the Treatment of As

FDA Approves Merck's DULERA(R) (mometasone furoate and formoterol fumarate dihydrate) Inhalation Aerosol for the Treatment of Asthma in Patients 12 Years of Age and Older

WHITEHOUSE STATION, N.J., Jun 24, 2010 (BUSINESS WIRE) -- Merck today announced that the U.S. Food and Drug Administration (FDA) has approved DULERA(R) (mometasone furoate and formoterol fumarate dihydrate) Inhalation Aerosol, a new fixed-dose combination asthma treatment for patients 12 years of age and older. DULERA is not indicated for the relief of acute bronchospasm. DULERA combines an inhaled corticosteroid (mometasone furoate) with a long-acting beta2-agonist (formoterol fumarate). The approval of DULERA is based, in part, on Phase III studies that evaluated the safety and efficacy of DULERA in patients 12 years of age and older with persistent asthma.

"Despite the advances made in the treatment of asthma in recent years, many patients may still not be well-controlled on their current therapies," said Michael S. Blaiss, M.D., clinical professor of pediatrics and medicine at the University of Tennessee Health Science Center, Memphis, Tennessee. "Asthma control is an important treatment goal and DULERA provides a new option for physicians to help manage this chronic condition in appropriate patients."

DULERA is indicated for the treatment of asthma in patients 12 years of age and older. DULERA is not indicated for the relief of acute bronchospasm.

Long-acting beta2-adrenergic agonists (LABA), such as formoterol, one of the active ingredients in DULERA, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, DULERA should only be used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue DULERA) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use DULERA for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

"As a leader in researching and developing new treatments for respiratory diseases, including asthma, Merck is committed to bringing forth medicines that help meet the needs of healthcare professionals and their patients," said James E. Fish, M.D., executive director, Global Scientific Affairs, Merck Research Laboratories. "DULERA represents an important part of this ongoing commitment."

DULERA is a pressurized metered-dose inhaler with a built-in numeric counter that shows the number of remaining doses. DULERA will be available for patients 12 years of age and older in two strengths: DULERA 100 mcg/5 mcg and DULERA 200 mcg/5 mcg. Each inhalation contains 5 mcg of formoterol fumarate and either 100 mcg or 200 mcg of mometasone furoate. The recommended starting dose is based on prior asthma therapy. The maximum daily recommended dose is two inhalations of DULERA 200 mcg/5 mcg twice daily every day in the morning and evening. DULERA is expected to be available in retail pharmacies nationwide by the end of July 2010.

Clinical Trials - Lung Function Measures

The approval of DULERA is supported, in part, by two randomized clinical trials (Trial 1, Trial 2) lasting 12 to 26 weeks in duration. These trials involved a total of 1,509 patients 12 years of age and older with persistent asthma uncontrolled on medium or high dose inhaled corticosteroids. These studies included a 2 to 3-week run-in period with mometasone furoate to establish a certain level of asthma control.

Trial 1 compared DULERA 100 mcg/5 mcg (n=191) to its individual components, mometasone furoate 100 mcg (n=192) and formoterol 5 mcg (n=202), and placebo (n=196). Trial 2 compared DULERA 200 mcg/5 mcg (n=255) with DULERA 100 mcg/5 mcg (n=233) and mometasone furoate 200 mcg (n=240). All medications were given as two inhalations twice daily by metered dose inhalers.

Results from both clinical trials showed patients receiving DULERA (100 mcg/5 mcg or 200 mcg/5 mcg) experienced significant improvement from baseline in lung function (mean area under the concentration-time curve for forced expiratory volume in 1 second, measured from 0 to 12 hours [FEV1 AUC0-12h]) at week 12, a primary efficacy endpoint in the trials, compared to mometasone furoate (Trial 1 and 2) and placebo (Trial 1). In Trial 1, these differences were maintained through week 26.

The change in mean trough FEV1 from baseline to week 12 was assessed as another endpoint in both trials. In Trial 1, a significantly greater increase in the mean trough FEV1 was observed for DULERA 100 mcg/5 mcg compared to formoterol 5 mcg (the primary treatment comparison) as well as to placebo. In trial 2, a greater numerical increase in the mean trough FEV1 were was observed for DULERA 200 mcg/5 mcg compared to DULERA 100 mcg/5 mcg and mometasone furoate 200 mcg.

Clinical Trials - Clinically Judged Deteriorations in Asthma or Reduction in Lung Function

Clinically judged deteriorations in asthma or reductions in lung function were assessed in Trial 1 as another primary endpoint to evaluate the contribution of mometasone furoate 100 mcg to DULERA 100 mcg/5 mcg (primary treatment comparison DULERA vs. formoterol). Deteriorations in asthma were defined as any of the following: a 20 percent decrease in FEV1; a 30 percent decrease in peak expiratory flow (PEF) on two or more consecutive days; emergency treatment, hospitalization, or treatment with systemic corticosteroids or other asthma medications not allowed per protocol. Fewer patients who received DULERA 100 mcg/5 mcg reported an event compared to patients who received formoterol 5 mcg (p<0.001).

In Trial 2, clinically judged deterioration in asthma or reduction in lung function was also assessed as an additional endpoint. Fewer patients who received DULERA 200 mcg/5 mcg or DULERA 100 mcg/5 mcg compared to mometasone furoate 200 mcg alone reported an event, using the same definition as Trial 1.

Clinical Trials - Safety Data

The most common treatment-emergent adverse events were nasopharyngitis, sinusitis and headache. These adverse events were reported at an incidence of greater than or equal to 3.0 percent and more commonly than placebo. Oral candidiasis has been reported in clinical trials at an incidence of 0.7 percent in patients using DULERA 100 mcg/5 mcg, 0.8 percent in patients using DULERA 200 mcg/5 mcg and 0.5 percent in the placebo group. Similar safety outcomes were observed in a long-term 52-week trial of patients 12 years of age and older receiving DULERA (100 mcg/5 mcg or 200 mcg/5 mcg) or active comparator. Dysphonia was observed at a higher frequency in the longer term treatment trial at a reported incidence of 7/141 (5%) patients receiving DULERA 100 mcg/5 mcg and 5/130 (3.8%) patients receiving DULERA 200 mcg/5 mcg.

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