FDA approves once-daily SEROQUEL XR Extended Release Tablets

AstraZeneca (NYSE: AZN) today announced that the US Food and Drug Administration (FDA) has approved once-daily SEROQUEL XR® (quetiapine fumarate) Extended Release Tablets as adjunctive (add-on) treatment to antidepressants in adults with Major Depressive Disorder (MDD). SEROQUEL XR is the only medication in its class approved by the FDA to treat both major depressive disorder as adjunctive therapy and acute depressive episodes associated with bipolar disorder as monotherapy.

MDD affects approximately 14.2 million American adults in a given year, and today it is often treated with antidepressants. Selective serotonin reuptake inhibitors, or SSRIs, are among the most commonly prescribed class of antidepressant medications for depression; however, in many cases patients fail to respond adequately to treatment. Results from a National Institute of Mental Health study, STAR*D, showed that approximately 63% of patients did not achieve remission with the SSRI citalopram when used as a first-line treatment(4). Additionally, this study reported that overall approximately one-third of patients with MDD failed to achieve study defined remission. This approval for SEROQUEL XR provides physicians with a new adjunctive treatment option for patients with MDD who have an inadequate response to their current antidepressant.

In addition to the FDA approval for the adjunctive indication in MDD, AstraZeneca has received a Complete Response Letter (CRL) from the FDA asking for additional information for the sNDAs for SEROQUEL XR as acute monotherapy and maintenance monotherapy for the treatment of MDD in adult patients.

AstraZeneca is evaluating the contents of the CRL. AstraZeneca will continue discussions with the FDA and will provide a response to the agency in due course. The CRL does not change the current recommendations for the treatment of patients taking SEROQUEL XR for approved indications in schizophrenia and bipolar disorder.

The FDA has required that AstraZeneca implement a Risk Evaluation and Mitigation Strategy (REMS). The REMS for SEROQUEL XR requires a Medication Guide and periodic assessments that will include a survey of patients' understanding of the potential risks of SEROQUEL XR. The REMS applies to all approved indications.

"Many people with major depressive disorder, despite being treated with currently approved medications, continue to experience depressive symptoms," said Dr. Richard Weisler. Adjunct Professor of Psychiatry at University of North Carolina School of Medicine and Adjunct Associate Professor at Duke University Medical Center. "SEROQUEL XR may provide another effective treatment option for the depressive symptoms associated with MDD as adjunctive treatment to antidepressants."

"Today's FDA approval of SEROQUEL XR is based on a clinical development program in MDD involving 939 patients randomized across two studies that assessed the efficacy and safety of once-daily treatment with SEROQUEL XR as adjunctive treatment to antidepressants," said Lisa Schoenberg, VP Specialty Care, AstraZeneca. "This new indication for SEROQUEL XR marks an important milestone in the treatment of MDD, as there is a significant need for additional options that may help patients with this devastating condition who are not adequately responding to their antidepressant therapy."

SEROQUEL XR is part of a class of drugs called atypical antipsychotics and is approved for a number of mental health disorders. In addition to today's approval for the adjunctive treatment of MDD, SEROQUEL XR is currently approved for the acute and maintenance treatment of bipolar disorder and schizophrenia.

Major Depressive Disorder sNDA Submission

The FDA approval of SEROQUEL XR for MDD was based on a supplemental new drug application (sNDA) comprising findings from two Phase III, placebo-controlled studies that assessed the efficacy and safety of once-daily treatment with SEROQUEL XR as adjunctive treatment in patients with MDD. Studies 6 and 7 were acute adjunctive therapy studies (with ongoing antidepressant therapy) involving 939 patients randomized (628 randomized to SEROQUEL XR) who had an inadequate response to their antidepressant therapy. Patients were on various antidepressants prior to study entry including SSRI's (paroxetine, fluoxetine, sertraline, escitalopram, or citalopram), SNRI's (duloxetine and venlafaxine), TCA (amitryptiline) and other (buproprion).

The primary endpoint in these studies was the change from baseline to end of treatment in the Montgomery-Asberg Depression Rating Scale(MADRS) total score. The recommended dose range of SEROQUEL XR in MDD is 150 to 300mg/day.

In both studies efficacy with SEROQUEL XR was superior to placebo, as assessed by the primary endpoints. SEROQUEL XR 300 mg once daily as adjunctive treatment to other antidepressant therapy was superior to antidepressant alone in reduction of MADRS total score in both trials. SEROQUEL XR 150 mg once daily as adjunctive treatment was superior to antidepressant therapy alone in reduction of MADRS total score in one trial. In these studies, the most commonly observed adverse reactions associated with the use of SEROQUEL XR (incidence of 5% or greater and at least twice that of placebo) were somnolence (150 mg: 37%, 300 mg: 43%), dry mouth (150 mg: 27%, 300 mg 40%), fatigue (150 mg: 14%, 300 mg: 11%) and constipation (150 mg only: 11%). The adverse events seen with SEROQUEL XR in these studies were generally consistent with the known profile of SEROQUEL XR in other indications.