Forest Announces Results of Recently Completed Lexapro(R) Pediatric Depression Clinical Trial

NEW YORK, Jun 24, 2004 /PRNewswire-FirstCall via COMTEX/ -- Forest Laboratories, Inc. (NYSE: FRX) announced today the results of a recently completed placebo- controlled study of Lexapro(R) (escitalopram oxalate) in children and adolescents. Patients receiving Lexapro did not demonstrate statistically significant separation from placebo in the primary efficacy measure, the mean change from baseline in the Children's Depression Rating Scale-Revised (CDRS-R) score.

The study was just completed and the safety data reported to the U.S. Food and Drug Administration (FDA). While data from the study are still being analyzed, initial results are being disclosed in this release.

The study found that Lexapro was well tolerated in both children and adolescents with no significant difference in withdrawal rates due to adverse events with Lexapro as compared to placebo. A separate analysis evaluating the frequency of suicide-related events and worsening of depression found that two placebo-treated patients reported suicide-related events and one placebo patient reported worsening of depression, whereas only one Lexapro-treated patient reported a suicide-related event and no Lexapro-treated patient reported worsening of depression. Forest believes the results of this trial in addition to the pediatric depression trials of citalopram (marketed as Celexa(R) in the U.S.) show that there is no added risk of suicidality or worsening of depression due to the use of these products in pediatric patients. There have been no suicides observed in the pediatric placebo- controlled clinical trial experience with either citalopram or Lexapro.

These initial analyses revealed positive trends in some of the secondary efficacy measures for the group of patients treated with Lexapro as compared to the placebo group.

Escitalopram is the single S-enantiomer form and therapeutically active component of the drug citalopram. There have been two pediatric, placebo- controlled clinical trials involving citalopram; one European trial in both hospitalized and outpatient adolescents, and one U.S. trial in child and adolescent outpatients.

In the European trial, citalopram did not show any improvement of depressive symptoms versus placebo. In contrast, the U.S. pediatric depression trial of citalopram showed a reduction of symptoms of depression to a significantly greater extent than placebo.

"It is important to better define the role antidepressants can play in treating this population," said Lawrence S. Olanoff, M.D., Ph.D., Executive Vice President and Chief Scientific Officer, Forest Laboratories, Inc. "The two U.S. studies are comparable in design and studied similar patient populations. We recognize that the European study is limited in its comparability to the U.S. experience due to its unique design and patient population -- which included both hospitalized patients and outpatients, many of whom had a history of more complicated depressive disorders. We believe that the aggregate safety and efficacy experience with Celexa and Lexapro in pediatric patients remains encouraging and that further study is warranted."

Forest plans to discuss with the FDA the initiation of new pediatric studies with Lexapro in the U.S. with the goal of ultimately achieving approval of its use in pediatric patients with major depressive disorder.

Lexapro Pediatric Study Details

Two hundred and sixty four patients, ages 6 to 17 with major depressive disorder and a CDRS-R score of 40 or greater, participated in the randomized, double-blind, multicenter, flexible dose study. Patients received either Lexapro (10-20 mg/day) or placebo treatment for up to 8 weeks. The primary efficacy measure was the mean change from baseline to week eight on the CDRS-R score. Secondary efficacy measures included the Clinical Global Impressions - Improvement (CGI-I) Scale, the Clinical Global Impressions - Severity (CGI-S) Scale, and the Children's Global Assessment Scale (CGAS). The initial results of the trial indicated that the change from baseline for the CGAS and the CGI-S scores appeared greater for the Lexapro treated group compared to the placebo group, however the differences did not quite achieve statistical significance (p= 0.07 and 0.06, respectively). When these same efficacy measures were analyzed for those subjects who remained in the study through the eight week assessment, statistically significant (p < 0.05) improvements were seen in the Lexapro group for both these assessments by comparison to the placebo group.

Lexapro was well tolerated in both pediatric and adolescent groups as compared to placebo treatment. No significant difference in drop-out rates due to adverse events compared to placebo was observed (1.5 % for both Lexapro-treated patients and placebo-treated patients). The incidence of patients with adverse events, including activation side effects, was similar between the Lexapro and placebo groups. Adverse events occurring at an incidence of >= 10% in patients treated with Lexapro or placebo respectively, included headache (22.9% and 21.8%), abdominal pain (10.7% and 5.3%), and menstrual cramps (4.4% and 10.1%).

About Lexapro

Lexapro is the newest and fastest-growing selective serotonin reuptake inhibitor (SSRI) and has been prescribed for more than 5 million patients in the U.S.

Lexapro was approved by the U.S. Food and Drug Administration in August 2002 for both the initial and maintenance treatment of major depressive disorder in adults and in December 2003 for the treatment of generalized anxiety disorder in adults.

The most common adverse events reported with Lexapro (reported at rates of approximately 5% or greater and 2 times or more the incidence seen in the placebo group) were nausea, insomnia, ejaculation disorder, somnolence, increased sweating, fatigue, decreased libido, and anorgasmia. Lexapro is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients with a hypersensitivity to escitalopram oxalate or any of the ingredients in Lexapro.

As with other SSRIs, caution is indicated in the co administration of tricyclic antidepressants (TCAs) with Lexapro. As with other psychotropic drugs that interfere with serotonin reuptake, patients should be cautioned regarding the risk of bleeding associated with the concomitant use of Lexapro with NSAIDs, aspirin, or other drugs that affect coagulation.

Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Although no causal role for antidepressants in inducing such behaviors has been established, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases.

Forest Laboratories licenses Lexapro from H. Lundbeck A/S, the Danish pharmaceutical firm that developed escitalopram and citalopram.

About Forest Laboratories and Its Products

Forest Laboratories' growing line of products includes: Lexapro(R), an SSRI antidepressant indicated for the initial and maintenance treatment of major depressive disorder and for generalized anxiety disorder; Celexa(R), an antidepressant; Namenda(R), an N-methyl-D-aspartate (NMDA)-receptor antagonist indicated for the treatment of moderate to severe Alzheimer's disease; Tiazac(R), a once-daily diltiazem, indicated for the treatment of angina and hypertension; Benicar(R),* an angiotensin receptor blocker indicated for the treatment of hypertension; Benicar HCT(TM), an angiotensin receptor blocker and diuretic combination product indicated for the second-line treatment of hypertension; and Aerobid(R), an inhaled steroid indicated for the treatment of asthma.

*Benicar(R) is a registered trademark of Sankyo Pharma, Inc.

Except for the historical information contained herein, this release contains "forward-looking statements" within the meaning of the Private Securities Reform Act of 1995. These statements are subject to risks and uncertainties that affect our business, including risk factors listed from time to time in the Company's SEC reports, including the Company's Annual Report on Form 10-K for the fiscal year ended March 31, 2004. Actual results may differ materially from those projected.

Photo Notes: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO

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