Lunesta Data Presented at 2005 American Psychiatric Association Meeting Poster Session

Main Category: Depression
Article Date: 27 May 2005 - 13:00 PDT

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Sepracor Inc (Nasdaq: SEPR) today announced that it has presented four LUNESTATM brand eszopiclone posters at the 158th annual meeting of the American Psychiatric Association (APA) in Atlanta.

Two LUNESTA posters reported the findings of a study in patients with co-existing insomnia and depression. Insomnia symptoms are reported in 65 percent to 90 percent of individuals with depression.1 An additional poster presented data on LUNESTA's effect on sleep parameters that impact next-day function, and the results of a crossover study evaluating the safety and efficacy of LUNESTA versus placebo were also presented.

Adjunctive Eszopiclone With Fluoxetine for Major Depressive Disorder (MDD) and Insomnia: Sleep Effects

The results of a Phase IIIB/IV, 545-patient, double-blind, placebo-controlled, ten-week study evaluating the efficacy and safety of eszopiclone in patients with major depressive disorder (MDD) and insomnia were presented. In this study, patients who met DSM-IV2 criteria for both insomnia and MDD (either newly diagnosed or patients who have relapsed), were randomized to receive open-label PROZAC(R) brand fluoxetine each morning and either double-blind eszopiclone 3 mg (n=270) or placebo (n=275) nightly for the first eight weeks, followed by a two-week period during which patients discontinued double-blind treatment but continued receiving fluoxetine.

In this study, patient-reported sleep and daytime function measures were assessed. Sleep efficacy was determined using patient-reported measures of time to sleep onset, wake time after sleep onset (WASO; a sleep maintenance measurement of the amount of time spent awake after initially falling asleep and the primary endpoint in this analysis) and total sleep time (TST). Sleep quality and depth, sense of physical well-being, daytime alertness, ability to function and ability to concentrate were also measured.

Averaged over the double-blind period, patients treated with eszopiclone showed statistically significant (p<0.05) improvements in time to sleep onset, WASO and TST, compared to those patients taking placebo. In this study, there was no evidence of tolerance to sleep efficacy (no waning of effect) across the eight weeks of treatment, and there was no rebound insomnia upon eszopiclone discontinuation.

Improvements in other measures of sleep and daytime function were statistically significant (p<0.05) for each parameter including sleep depth, sleep quality, alertness, ability to concentrate, sense of physical well-being and ability to function.

Adjunctive Eszopiclone With Fluoxetine for MDD and Insomnia: Depression Effects The Phase IIIB/IV, 545-patient, double-blind, placebo-controlled, ten-week study evaluating the efficacy and safety of eszopiclone in patients with MDD and insomnia also assessed antidepressant efficacy, and the results were presented separately in the poster session.

In this study, antidepressant efficacy was assessed using patient-reported depression measures and clinician-administered measures, including HAM-D17 (Hamilton Depression Rating Scale, the standard scale used by clinicians to assess depression; HAM-D17 is a list of symptoms commonly associated with depression) and Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales (used by clinicians to subjectively assess improvement in a patient's symptoms and the severity of their depression, respectively).

In this study, co-administration of eszopiclone with fluoxetine resulted in statistically significant reductions in clinician-evaluated overall HAM-D17 scores at Week 4 (p< or =0.01) with a statistically significant, progressive improvement at Week 8 (p< or =0.002), versus the placebo-fluoxetine control group. After removing insomnia-specific questions from HAM-D17, improvements in scores remained significant at Week 8. At Week 8, significantly more eszopiclone-treated patients were responders (patients experiencing a 50 percent or greater decrease in their HAM-D17 scores; p=0.01) and remitters (patients who have HAM-D17 scores of 7 or lower and are therefore considered to no longer be depressed; p=0.03). Patient-reported depression measures showed more improvement in the eszopiclone co-administration group than in the placebo-fluoxetine control group, but these differences were not statistically significant.

Additionally, fewer patients receiving eszopiclone and fluoxetine therapy (45%) required titration to a higher dose of fluoxetine as compared to those in the placebo-fluoxetine control group (54%). CGI-I and CGI-S scores were significantly improved with eszopiclone co-administration. These statistically significant differences (p< or =0.01) were noted beginning at Week 1 and Week 2, respectively, and were maintained through the 8-week treatment period. Study completion rates were similar in both the placebo- and eszopiclone-treated groups and eszopiclone and fluoxetine co-administration was well tolerated.

Effect of Eszopiclone on Sleep Parameters that Affect Next-Day Function

Analysis of data from a randomized, double-blind, placebo-controlled, parallel-group study of 264 elderly (65-85 years of age) patients with a DSM- IV diagnosis for primary insomnia assessed the correlation between nighttime sleep and next-day function, and calculated the percent of the treatment effect of eszopiclone on next-day function due to improved sleep. Patients received either eszopiclone 2 mg or placebo nightly for two weeks.

Data for the patients who received eszopiclone showed that a correlation exists between improvements in patient-reported measures of next-day function and improvements in both objective (measured by polysomnography, or PSG; a sleep laboratory assessment) and patient-reported sleep parameters such as TST, WASO, sleep latency (time to sleep onset) and number of awakenings.

Additionally, patient-reported improvements in sleep quality and sleep depth correlated best with improvements in next-day function. The effect of eszopiclone 2 mg on improvements in next-day function in this elderly population was largely explained by improvements in nighttime sleep.

A Crossover Study of Eszopiclone in the Treatment of Primary Insomnia

The results of a multicenter, double-blind, placebo-controlled, six-way crossover study evaluating the efficacy and safety of eszopiclone versus placebo in 65 adults with a DSM-IV diagnosis for primary insomnia showed that, based on sleep parameters measured objectively using PSG, eszopiclone statistically significantly reduced latency to persistent sleep (also known as time to sleep onset; p< or =0.0001) and increased sleep efficiency (p< or =0.05) versus placebo. Patients in this study received two nights of treatment with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg and 3 mg, or AMBIEN(R) brand zolpidem 10 mg in a random order. Zolpidem was included as an active control in this study. Visits were separated by a three- to seven-day washout period.

All eszopiclone doses and zolpidem were effective in reducing time to sleep onset and improving sleep efficiency when compared to those patients treated with placebo. In this study, only eszopiclone 2.5 mg and 3 mg had a significant (p< or =0.05) impact on PSG measures of sleep maintenance, including WASO, wake time during sleep and number of awakenings, when compared to placebo. In addition, only eszopiclone 2.5 mg and 3 mg significantly reduced morning sleepiness when compared to placebo. In this study, all treatment arms were generally well tolerated.

About LUNESTA

LUNESTA is a new non-benzodiazepine indicated for the treatment of insomnia in patients who experience difficulty falling asleep as well as for the treatment of patients who have difficulty sleeping through the night (sleep maintenance difficulty). LUNESTA is approved for long-term use. LUNESTA 1 mg, 2 mg and 3 mg tablets are available by prescription in pharmacies nationwide.

An estimated 100 million adult Americans suffer from either chronic or occasional insomnia.3 Symptoms of insomnia include difficulty falling asleep, awakening frequently during the night, waking up too early, an inability to fall back to sleep or awakening feeling unrefreshed.

Important Safety Information

LUNESTA works quickly and should only be taken immediately before bedtime. Be sure you have at least eight hours to devote to sleep before becoming active. You should not engage in any activity after taking LUNESTA that requires complete alertness, such as driving a car or operating machinery. You should use extreme care when engaging in these activities the morning after taking LUNESTA. Do not use alcohol while taking any sleep medicine. All sleep medicines carry some risk of dependency. Do not use sleep medicines for extended periods without first talking to your doctor. Side effects may include unpleasant taste, headache, drowsiness and dizziness.

Please visit sepracor.com or lunesta.com to access the FDA-approved labeling text for LUNESTA.

About Sepracor

Sepracor Inc. is a research-based pharmaceutical company dedicated to treating and preventing human disease through the discovery, development and commercialization of innovative pharmaceutical products that are directed toward serving unmet medical needs. Sepracor's drug development program has yielded an extensive portfolio of pharmaceutical compound candidates with a focus on respiratory and central nervous system disorders. The company's commercialization efforts are carried out by its U.S.-based, 1,250-person, primary care and specialty-oriented sales force. Sepracor's corporate headquarters are located in Marlborough, Massachusetts.

This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to the safety, efficacy and potential benefits of LUNESTA. 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, and the results of, further clinical trials; the timing and success of submission, acceptance and approval of additional regulatory filings; label/use changes or concerns of LUNESTA prescribers or patients; and certain other factors that are detailed in the company's quarterly report on Form 10-Q for the quarter ended March 31, 2005 filed 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.

Lunesta is a trademark of Sepracor Inc. Ambien is a registered trademark of sanofi-aventis Corporation. Prozac is a registered trademark of Eli Lilly and Company.

(1) Perlis ML, Giles DE, Buysse DJ, Tu X, Jupfer DJ. Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord 1997:42;209-212 and McCall WV, Reboussin BA, Cohen W. Subjective measurement of insomnia and quality of life in depressed inpatients. J Sleep Res 2000;9:43-48.

(2) Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition

(3) Extrapolated to current population from 2000 census based on Ancoli- Israel et al. SLEEP. 1999;22 (suppl 2):S347-S353.

For a copy of this release or any recent release, visit http://www.sepracor.com.

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding Sepracor Inc.'s business which are not historical facts are "forward-looking statements" that involve risks and uncertainties. For a discussion of such risks and uncertainties, which could cause actual results to differ from those contained in the forward-looking statements, see "Risk Factors" in the Company's Annual Report or Form 10-K for the most recently ended fiscal year.