Results of Studies of Alvesco for the Treatment of Asthma and Omnaris in an HFA Nasal Aerosol Presented at American College of Allergy, Asthma & Immunology Annual Meeting
MARLBOROUGH, Mass.--(BUSINESS WIRE)--Nov 10, 2008 - Sepracor (Nasdaq: SEPR) today announced the presentation of Phase III study data for ALVESCO(R) (ciclesonide) HFA Inhalation Aerosol and Phase I data for a ciclesonide HFA MDI nasal aerosol formulation for the treatment of allergic rhinitis. These results were presented at the Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI) in Seattle.
Ciclesonide HFA MDI Nasal Aerosol Trial
The results of a 14-day, randomized, double-blind, placebo-controlled, 3-period crossover, single-center study in healthy volunteers (n=17) and patients with perennial allergic rhinitis (n=18) were orally presented. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of two dosages (150 mcg and 300 mcg) of an HFA MDI formulation of the intranasal corticosteroid. In this study, systemic exposure to des-ciclesonide, which is the activated form of ciclesonide, was found to be low and similar in both healthy volunteers and patients with perennial allergic rhinitis, with no evidence of systemic accumulation over the study period. In this study, no significant effect on HPA-axis (hypothalamic-pituitary-adrenal axis; a significant part of the neuroendocrine system, which regulates several body functions) function was observed following treatment with ciclesonide HFA nasal aerosol as measured by comparable serum cortisol levels in both the ciclesonide HFA nasal aerosol and placebo groups. Both dosages of ciclesonide HFA nasal aerosol were well tolerated.
Sepracor recently initiated Phase III development for ciclesonide in an HFA nasal aerosol for the treatment of allergic rhinitis. OMNARIS is currently available in the U.S. in a hypotonic aqueous suspension nasal spray for the treatment of allergic rhinitis.
ALVESCO HFA Phase III Trial in Patients Not Previously Treated With an Inhaled Corticosteroid
The results of a 691-patient, double-blind, placebo-controlled, parallel-group, multicenter study of patients 12 years of age and older were summarized in three posters at the conference. In this study, patients received either:
-- ALVESCO 80 mcg twice daily (BID) for 16 weeks;
-- ALVESCO 160 mcg once daily (QD) in the morning for 16 weeks;
-- ALVESCO 80 mcg BID for four weeks followed by ALVESCO 160 mcg QD in the morning for 12 weeks; or
-- Placebo for 16 weeks.
The study was comprised of patients who demonstrated FEV1(a) of > or = 60 to < or = 85 percent of predicted lung function and who were determined to have uncontrolled asthma based on symptom scores, rescue inhaler use and peak expiratory flow measurements. The study demonstrated that patients who were treated with ALVESCO 80 mcg BID or ALVESCO 160 mcg QD experienced improved pulmonary function versus those patients administered placebo. In this study, ALVESCO HFA was well tolerated.
Each of the ALVESCO treatment groups (ciclesonide 80 mcg BID p less than 0.0001; ciclesonide 160 mcg QD p=0.0021; ciclesonide 80 mcg BID + 160 mcg QD p=0.0016) demonstrated significantly improved FEV1 from baseline to the average of Weeks 12 and 16, compared to the placebo group (300 mL for ciclesonide 80 mcg BID; 180 mL for ciclesonide 160 mcg QD; 190 mL for ciclesonide 80 mcg BID + 160 mcg QD; and 70 mL for placebo at Week 16). Each of the ALVESCO treatment groups (ciclesonide 80 mcg BID p less than 0.0001; ciclesonide 160 mcg QD p=0.0006; ciclesonide 80 mcg BID + 160 mcg QD p less than 0.0001) also demonstrated significantly improved morning peak expiratory flow from baseline to Week 16 versus the placebo group.
All ALVESCO treatment groups (ciclesonide 80 mcg BID p less than 0.0001; ciclesonide 160 mcg QD p=0.0116; ciclesonide 80 mcg BID + 160 mcg QD p=0.0002) significantly reduced rescue racemic albuterol use from baseline to Week 16 versus the placebo group. The ALVESCO 80 mcg BID group (p=0.0002) and the ALVESCO 80 mcg BID + 160 mcg QD group (p=0.0325) demonstrated significant improvement in total daily asthma symptom scores versus placebo, but the reduction for the ALVESCO 160 mcg QD treatment group was not significantly different from placebo. Reduction in nighttime awakenings from baseline to Week 16 versus placebo was also significant for the ALVESCO 80 mcg BID group (p=0.004) versus placebo, but not for the other ALVESCO treatment groups.
Treatment-emergent adverse events (TEAEs) were comparable for all treatment groups, were predominantly mild-to-moderate in intensity and considered unrelated to study treatment, and the frequency of TEAEs leading to withdrawal from the study were greater in the placebo group (n=22; 12.4%) than any of the ALVESCO treatment groups (ciclesonide 80 mcg BID: n=4, 2.3%; ciclesonide 160 mcg QD: n=14, 8.0%; ciclesonide 80 mcg BID + 160 mcg QD: n=8, 4.6%) . The incidence of asthma adverse events was low in the ALVESCO treatment groups (ciclesonide 80 mcg BID: n=9, 5.2%; ciclesonide 160 mcg QD: n=14, 8.0%; ciclesonide 80 mcg BID + 160 mcg QD: n=18, 10.4%; placebo: n=25, 14.0%), and the percentage of patients with oropharyngeal/laryngeal adverse events (such as oral candidiasis, dysphonia and pharyngolaryngeal pain) was low and comparable for each of the treatment groups. There were no reports of oral candidiasis in the study and two reports of dysphonia (one in the placebo group and one in the ciclesonide 160 mcg QD group) in this study.
ALVESCO HFA Phase III Trial in Patients Previously Using Another Inhaled Corticosteroid
A multicenter, double-blind, placebo-controlled, parallel-group study of 446 patients 12 years of age and older with mild-to-moderate persistent asthma who had previously been treated with another inhaled corticosteroid were randomized for 12 weeks of treatment. Patients in this study received either:
-- ALVESCO 80 mcg BID;
-- ALVESCO 160 mcg QD in the morning; or
In this study, both ALVESCO 80 mcg BID and ALVESCO 160 mcg QD were well tolerated in patients switched from a different inhaled corticosteroid or a combination inhaled corticosteroid product.
In contrast to the placebo treatment arm, both ALVESCO dosage regimens maintained FEV1 at each post-randomization time point, including at Week 12, which was the primary efficacy endpoint. At Week 12, the ALVESCO 80 mcg BID and ALVESCO 160 mcg QD treatment arms had improved by 60 mL and 20 mL, respectively, while FEV1 in the placebo treatment arm had declined by 110 mL from baseline (p less than 0.001 for each comparison). The ALVESCO dosage regimens also differentiated from placebo treatment at each earlier time point (p less than 0.005 for each comparison). A significantly (p less than 0.0001) lower proportion of patients in the ALVESCO 80 mcg BID (4.0%) and the ALVESCO 160 mcg QD (5.3%) groups withdrew from the study due to lack of efficacy or an asthma exacerbation as compared to the placebo (21.8%) group.
For both ALVESCO treatment groups, mean daily rescue racemic albuterol use was stable at Week 12 compared to baseline as compared to an increase in the placebo group. Reductions in racemic albuterol use at Week 12 compared to baseline were statistically significant in the ALVESCO 80 mcg BID group (p less than 0.0001), but not in the ALVESCO 160 mcg QD group, versus the placebo treatment group. At each study visit, asthma symptom scores were lower versus baseline for each ALVESCO treatment group and higher for the placebo group, and at Week 12, reductions in asthma total symptom scores were statistically significant in the ALVESCO 80 mcg BID group (p=0.0011), but not in the ALVESCO 160 mcg QD group, versus the placebo group. The number of nighttime awakenings was stable for both ALVESCO treatment groups from baseline to Week 12, and there was a numerically greater increase in nighttime awakenings in the placebo group, but the differences versus placebo were not statistically significant.
TEAEs were similar across all treatment groups (ciclesonide 80 mcg BID: n=79, 52.0%; ciclesonide 160 mcg QD: n=88, 57.9%; placebo: n=84, 55.3%) with most being mild-to-moderate in intensity and determined to be unrelated to study medication. The placebo group demonstrated the highest proportion of asthma adverse events (ciclesonide 80 mcg BID: n=5, 3.3%; ciclesonide 160 mcg QD: n=7, 4.6%; placebo: n=27, 17.8%), while the ALVESCO groups demonstrated higher proportions of nasopharyngitis (ciclesonide 80 mcg BID: n=14, 9.2%; ciclesonide 160 mcg QD: n=19, 12.5%; placebo: n=9, 5.9%). In the study, 39 patients withdrew from the study due to adverse events with the majority being in the placebo treatment group (n=24), and the most common reasons were worsening asthma or upper respiratory tract infection. Oropharyngeal adverse events were comparable across treatment groups (ciclesonide 80 mcg BID: n=10, 6.6%; ciclesonide 160 mcg QD: n=10, 6.6%; placebo: n=6, 4.0%). One case of oral candidiasis (ciclesonide 80 mcg BID group) and one case of dysphonia (ciclesonide 160 mcg QD group) were reported during the trial.
About OMNARIS Nasal Spray
OMNARIS (ciclesonide) Nasal Spray is the intranasal formulation of ciclesonide for the treatment of nasal symptoms associated with seasonal allergic rhinitis in adults and children 6 years of age and older, and with perennial allergic rhinitis in adults and adolescents 12 years of age and older. Intranasal corticosteroids are well accepted as first-line therapy for the treatment of allergic rhinitis, and they work by reducing inflammation - the major underlying cause of the clinical symptoms. OMNARIS Nasal Spray was shown to have a favorable safety profile. The most frequently reported adverse events seen with OMNARIS Nasal Spray were headache, epistaxis, nasopharyngitis, ear pain, and pharyngolaryngeal pain. The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. Intranasal corticosteroids may cause a reduction in growth velocity when administered to pediatric patients.
For additional information about OMNARIS Nasal Spray, please visit www.omnaris.com.
About ALVESCO HFA
ALVESCO (ciclesonide) HFA Inhalation Aerosol is an inhaled corticosteroid that reduces inflammatory processes and is indicated for use in adolescent and adult asthma patients 12 years of age and older with recommended twice-daily dosing. The active ingredient in ALVESCO HFA is ciclesonide. ALVESCO HFA has wide inhibitory activities against multiple inflammatory cell types and chemicals involved in the asthmatic response.
ALVESCO HFA should be used regularly as prescribed. The effectiveness of the medication depends on its regular use. It may take 4 weeks or longer before a patient feels the full benefits of ALVESCO HFA. Patients should not increase their prescribed dosage; if symptoms do not improve or asthma symptoms worsen, patients should contact their doctor.
ALVESCO HFA is not a bronchodilator and is not intended to provide rapid relief of breathing difficulties during an asthma attack. Patients should not use ALVESCO HFA if they are experiencing sudden symptoms of shortness of breath. Patients should use an inhaled short-acting bronchodilator, or rescue medication, such as levalbuterol, to relieve sudden symptoms of shortness of breath. Patients using doses of corticosteroid drugs that weaken the immune system are more susceptible to infection and should avoid exposure to chickenpox and/or measles. ALVESCO HFA can worsen existing conditions such as tuberculosis (TB), herpes of the eye, and other infections.
Orally inhaled corticosteroids, including ALVESCO HFA, may cause slowed growth in children and adolescents. These patients should have their growth monitored regularly.
Yeast infections in the mouth and throat (thrush) have occurred in some patients treated with ALVESCO HFA. Eye problems have been reported following the use of inhaled corticosteroids including ALVESCO HFA. Patients should speak to their doctor if they have a history of eye problems or experience a change in vision.
For more information about ALVESCO HFA, please visit www.alvesco.us, or click here.
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 large and growing markets and 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. Currently marketed products include LUNESTA(R) brand eszopiclone, XOPENEX(R) brand levalbuterol HCl Inhalation Solution, XOPENEX HFA(R) brand levalbuterol tartrate Inhalation Aerosol, BROVANA(R) brand arformoterol tartrate Inhalation Solution, OMNARIS brand ciclesonide Nasal Spray and ALVESCO brand ciclesonide HFA Inhalation Aerosol. Sepracor's corporate headquarters are located in Marlborough, Massachusetts.
(a) Forced expiratory volume in one second; a test of lung function.
OMNARIS is a trademark and ALVESCO is a registered trademark of Nycomed GmbH. LUNESTA, XOPENEX, XOPENEX HFA and BROVANA are registered trademarks of Sepracor Inc. For a copy of this release or any recent release, visit Sepracor's web site at www.sepracor.com.
JonaÃ© R. Barnes, 508-481-6700
Sr. Vice President, Investor Relations
and Corporate Communications
Posted: November 2008