Shire plc, the global specialty biopharmaceutical company, announced results from a phase-2 signal finding study of Vyvanse [lisdexamfetamine dimesylate (or SPD489)] in patients who have had residual symptoms of depression following treatment with Lexapro (escitlopram) for Major Depressive Disorder (MDD). Based on these findings, Shire intends to advance discussions with regulators to explore the development of program parameters for additional studies of Vyvanse as adjunctive therapy to primary anti-depressant treatments in patients with MDD.    

Vyvanse is a prescription medicine currently approved in the US for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Efficacy was based on two controlled trials in children aged six to 12 and two controlled trials in adults. Vyvanse should be used as part of a total treatment program that may include counseling or other therapies.

Vyvanse is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep Vyvanse in a safe place to prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is against the law. Vyvanse is a stimulant medication. Misuse of stimulants may cause sudden death and serious cardiovascular adverse events.

In this investigational 14-week, double-blind, randomized, placebo-controlled study (n=246), Vyvanse was administered orally as an adjunctive therapy for six weeks to adults between the ages of 18 and 55, who continued to experience symptoms of depression following a prospective eight-week treatment period with 20 mg/day of escitalopram/Lexapro. Continuing symptoms were defined as a total HAM-D17 score= 4 at the end of this prospective phase (n=177). In the randomized period, eligible subjects received escitalopram plus either placebo or Vyvanse (dose optimized over the range of 20 to 50 mg per day) on a 1:1 basis.

The primary study endpoint was the mean change in the total MADRS score after 6 weeks of blinded treatment in the non-remitter subset (n=129) of the randomized population, defined as subjects with a total MADRS score of >10 after the 8 week escitalopram treatment. The significance level was prospectively set at 10%.

Vyvanse demonstrated improvement compared to placebo on the mean total MADRS of  -2.3 [90% CI -4.5 to -0.1] after six weeks of treatment in the primary analysis of non-remitting subjects (p=0.090). An additional pre-planned analysis was conducted among subjects who had a total MADRS score >10 and achieved < 50% improvement in total MADRS score (n=86). This analysis found an endpoint LS mean difference between Vyvanse and placebo of -3.9 [90% CI -6.5 to -1.3; p=0.0132 (not adjusted for multiplicity)]. The most commonly reported adverse events (dry mouth, headache, decreased appetite, and insomnia) in the trial were consistent with the known, labelled profile of Vyvanse in ADHD. Mean blood pressure and mean heart rate changes were also consistent with the product label. No notable mean ECG changes or mean changes in clinical laboratory assessments were reported in this study. The mean dose per day of Vyvanse used for adjunctive therapy with escitalopram was 29.6 mg.

“Only about 30 to 33 percent of patients will achieve full symptom remission with the first step standard antidepressant treatment,” said Madhukar H Trivedi, professor of Psychiatry at University of Texas Southwestern Medical School. “Therefore, almost two-thirds of patients starting an antidepressant will need a second or third step treatment to achieve symptom relief.  We are encouraged by the signal findings we’ve seen in this phase-2 study and look forward to further evaluating Vyvanse for adjunctive treatment of patients with inadequate response to treatment in MDD.”

Vyvanse is a prescription medicine for the treatment of ADHD. Efficacy was based on two controlled trials in children aged six to 12 and two controlled trials in adults.