PRINCETON, NJ and TOKYO, JAPAN, November 20, 2007 Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka Pharmaceutical Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application for ABILIFY(R)(aripiprazole) as adjunctive, or add-on, treatment to antidepressant therapy (ADT) in adults with major depressive disorder (MDD). ABILIFY is the first medication approved by the FDA as add-on treatment for MDD.
The approval of this new add-on treatment option is critical for adults suffering from depression who cannot find sufficient relief for their symptoms with antidepressants alone, said Madhukar Trivedi, M.D., Professor and Chief-Division of Mood Disorders, University of Texas Southwestern Medical School, Dallas, Texas. Now physicians have a proven new option they can add to their patients antidepressant treatments to help them feel better and relieve unresolved depressive symptoms.
The approval is based on results from two six-week, double-blind, randomized, placebo-controlled, multicenter studies (n=743). The results from both studies demonstrated significant improvement in depressive symptoms in adult patients with a primary diagnosis of major depressive disorder who had experienced an inadequate response* to monotherapy with one or more ADTs in the current episode and then added ABILIFY to their treatment regimens.
We are committed to helping those who suffer from depression, one of the leading causes of disability in the United States and worldwide, said Elliott Sigal, M.D., Ph.D., Executive Vice President, Chief Scientific Officer and President, Research and Development, Bristol-Myers Squibb. This approval is a reflection of our ongoing commitment to provide innovative therapies, such as ABILIFY, to help adults living with depression.
We are pleased that ABILIFY has achieved this important milestone as the first medication approved as adjunctive treatment for adults with major depressive disorder, said Taro Iwamoto, Ph.D., Chief Executive Officer, President and Chief Operating Officer, Otsuka Pharmaceutical Development and Commercialization, Inc. This new add-on treatment option for depression represents hope for many adults suffering from this debilitating illness.
Major depressive disorder affects millions of U.S. adults at some point in their lives.(2) A recent study evaluated different treatment approaches, including adjunctive medications and switching strategies, in patients with MDD.(1) The study found that 63 percent of patients did not achieve adequate relief of depressive symptoms following the initial treatment with an antidepressant alone.(1) Additionally, the study demonstrated that the use of adjunctive medications in treatment may be useful to improve unresolved depressive symptoms.(1)
Clinical Trial Design and Findings
Two six-week, double-blind, randomized, placebo-controlled, multicenter studies evaluated the efficacy and safety of add-on ABILIFY in adult patients with a primary diagnosis of major depressive disorder who had experienced an inadequate response to prior antidepressant therapy (one to three courses) in the current episode.
After an eight-week prospective treatment phase with one ADT plus single-blind placebo to confirm inadequate response to ADT, 743 participants entered a six-week randomized treatment phase during which they continued their ADT plus double-blind adjunctive placebo or adjunctive ABILIFY. All study participants received one of the commonly prescribed ADTs, including selective serotonin reuptake inhibitors (SSRIs): Lexapro(R) (escitalopram), Prozac(R) (fluoxetine), Paxil CR(R) (paroxetine controlled-release), Zoloft(R) (sertraline); or a serotonin-norepinephrine reuptake inhibitor (SNRI): Effexor XR(R) (venlafaxine extended release). The dosage range for adjunctive ABILIFY was 2-20 mg/day (15 mg/day was the maximum dose for patients receiving ABILIFY as an adjunct to Paxil CR or Prozac).
The primary efficacy endpoint was the mean change from baseline the end of the prospective treatment phase to the end of the randomized treatment phase in a standard measure called Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale used to assess depressive symptoms. A reduction in MADRS Total Score represents an improvement in depressive symptoms. The key secondary endpoint was the Sheehan Disability Scale (SDS), a three-item self-rated instrument used to assess the impact of depression on three domains of functioning (work/school, social life and family life) with each item scored from zero (not at all) to 10 (extreme). Safety evaluations included incidence of adverse reactions, discontinuation rate due to adverse reactions and laboratory measures.
For the primary endpoint, both studies showed that taking ABILIFY plus an ADT provided superior improvement in depressive symptoms to ADT alone at study endpoint (week six), as measured by the reduction of the MADRS Total Scores.(3) For the secondary endpoint, ABILIFY plus an ADT was also superior to placebo plus ADT in reducing the mean SDS Total Score in one study.
In these studies, adjunctive ABILIFY demonstrated no clinically important differences on metabolic parameters, including prolactin, fasting glucose, HDL, LDL and total cholesterol. The median percent change from baseline in triglycerides was 5 percent for adjunctive ABILIFY-treated patients vs 0 percent for adjunctive placebo-treated patients. In the studies, weight gain greater than or equal to 7 percent increase from baseline was seen in 5 percent of adult patients treated with adjunctive ABILIFY and 1 percent of adjunctive placebo-treated patients. The mean change from baseline in weight was 1.7 kilograms (kg) for adjunctive ABILIFY and 0.4 kg for adjunctive placebo.
In a pool of two placebo-controlled trials of patients, the rate of discontinuation due to adverse reactions with the use of adjunctive ABILIFY compared to placebo plus ADT was 6 percent vs 2 percent, respectively. The most commonly observed adverse reactions (incidence greater than or equal to 5 percent and at least twice the incidence of placebo plus ADT) associated with the use of adjunctive ABILIFY were akathisia (25 percent vs 4 percent), restlessness (12 percent vs 2 percent), insomnia (8 percent vs 2 percent), constipation (5 percent vs 2 percent), fatigue (8 percent vs 4 percent) and blurred vision (6 percent vs 1 percent).
About Major Depressive Disorder
Major depressive disorder is a serious mental illness(4) characterized by one or more major depressive episodes.(5) Depression affects approximately 13 to 14 million adults,(2) or about 6.7 percent of the adult population in a given year,(6) and is one of the most common mental health disorders.(7) Depression is one of the leading causes of disability in the U.S.(8) In 2000, the total economic burden of treating depression in the U.S. was $83.1 billion, with workplace costs, including missed days and lack of productivity due to illness, accounting for the majority of the total economic burden (62 percent).(9) Other economic burdens in 2000 included $26.1 billion (31 percent) for treatment costs and $5.4 billion (7 percent) for suicide-related costs.(9)
About ABILIFY (aripiprazole)
The first and only available dopamine partial agonist, ABILIFY is indicated as adjunctive treatment to antidepressant therapy in adults with major depressive disorder.
Initially approved in November 2002, over 12.5 million prescriptions have been written for ABILIFY in the U.S.(10) through June 2007.
ABILIFY is available by prescription only. ABILIFY Tablets should be taken once daily with or without food and are available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg strengths. As adjunctive treatment to antidepressant therapy in adults with major depressive disorder, ABILIFY Oral starting dose is 2 mg/day to 5 mg/day with a maximum dose of 15 mg/day. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than one week.
|Contact: David M. Rosen|