(dailyRx News) Eli Lilly has announced that the FDA has approved a new indication for Symbyax (olanzapine and fluoxetine HCl). It's now the first drug approved by the agency for the acute treatment of treatment-resistant depression (TRD).
"Living with major depressive disorder is difficult and distressing for anyone, but even more so for patients whose symptoms continue despite treatment," said Eli Lilly Medical Director Dr. Sara Corya. "Until today, there has been no approved medication for treatment-resistant depression. Now, after two failed attempts with other antidepressants, doctors and patients have a new treatment option."
In other actions, the FDA approved two new combination indications for Zyprexa (olanzapine) and fluoxetine for the acute treatment of bipolar depression and TRD. Eli Lilly originally developed Prozac (fluoxetine HCl).
The new Symbyax TRD indication is for acute treatment of adult patients with major depressive disorder who have not responded to two separate trials of different antidepressants of adequate dose and duration in their current episode. Symbyax was the first drug approved by the FDA for acute treatment of bipolar depression in adults in 2003.
Zyprexa, in combination with fluoxetine, is now approved for the acute treatment of TRD in adults. It's also approved for the acute treatment of bipolar depression in adults.
Neither Zyprexa nor fluoxetine are indicated as monotherapy for bipolar depression or TRD.
Supporting Study Details
The data package submitted to the FDA supporting the approval of Symbyax for TRD as well as the approval of Zyprexa in combination with fluoxetine for TRD included one pivotal trial and data from three supportive trials and one inconclusive trial. Acute safety information was based on a total of 10 studies. Doses evaluated in these studies ranged from 6 to 18 mg for olanzapine and 25 to 50 mg for fluoxetine in fixed combination.
An eight-week randomized, double-blind, controlled study was conducted to evaluate the efficacy of Symbyax in patients who met the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD) and did not respond to two antidepressants of adequate dose and duration in their current episode. Patients who were not responding to an antidepressant in their current episode entered an eight-week open-label fluoxetine lead-in and then were randomized to receive an eight-week trial of Symbyax, olanzapine or fluoxetine. Symbyax was flexibly dosed between 6/50 mg, 12/50 mg and 18/50 mg (olanzapine/fluoxetine dose).
Results from this study yielded a greater statistically significant reduction in mean total Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline to endpoint for Symbyax versus fluoxetine and olanzapine alone.
A second study of 28 patients who met the same criteria for TRD demonstrated statistically significant greater reductions in MADRS scores for Symbyax versus fluoxetine and olanzapine alone.
A third study demonstrated statistically significant greater reductions in total MADRS scores for Symbyax versus fluoxetine or olanzapine alone when analyzed in a subpopulation of depressed patients who met the same criteria for treatment resistance.
Of the two additional studies included in the sNDA data package, one provided statistically significant supporting data for Symbyax in the acute treatment of TRD, while the other was inconclusive.
An integrated analysis of all five studies provided to the FDA yielded a statistically significant greater reduction in mean total MADRS scores from baseline to endpoint in the defined population for patients treated with Symbyax versus fluoxetine and olanzapine and greater statistically significant remission rates for patients treated with Symbyax (25.5 percent) versus fluoxetine (17.3 percent) and olanzapine (14 percent).
Adverse events reported in 5 percent or more of Symbyax-treated patients in these trials and at twice the rate of placebo were weight gain, increased appetite, dry mouth, drowsiness and fatigue.
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