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H Lundbeck A/S (Lundbeck) and partner Takeda Pharmaceutical Company Limited (Takeda) have announced that the companies will be presenting new data on four pivotal studies on vortioxetine, a novel investigational drug under review by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of major depression.
The phase III data will be presented at the 2013 Annual Meeting of the American Psychiatric Association (APA) in San Francisco, USA.
The objective of these four studies was to evaluate the efficacy and safety profile of vortioxetine in doses ranging from 10–20mg per day, complementing other studies in the New Drug Application (NDA) submission package that included dose ranges of 5–20mg per day.
Three of the four pivotal studies met the primary efficacy endpoint as measured by the change from baseline of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8. Statistically significant improvements in overall symptoms of depression were demonstrated, as compared to placebo. A fourth study did not meet the primary endpoint. Results of all four studies provided additional information regarding the safety profile of vortioxetine.
“It is important that we continue to seek new options in depression because, even though there are effective treatments available, many patients remain symptomatic,” said Madhukar Trivedi, MD, professor of psychiatry, UT Southwestern Medical Center. “As a clinician, I’m encouraged by these data. They represent an important addition to the broader clinical profile for vortioxetine and support its potential as a new treatment for patients with MDD.”
Dr. Trivedi, director of UT’s Southwestern Depression Center, serves as scientific advisor for Lundbeck and Takeda.
About the studies
The studies were multicentre, randomised, double-blind, parallel-group trials of adult patients taking vortioxetine designed to assess improvement in overall symptoms of depression at week 8 with vortioxetine, compared to placebo. Two studies included an established depression therapy, duloxetine, as an active reference arm. The four studies were also conducted to assess and provide further information on vortioxetine’s safety profile.
A Duloxetine-referenced Fixed Dose Study Comparing Efficacy and Safety of 2 Vortioxetine Doses in the Acute Treatment of Adult MDD Patients (Study 315 conducted in the US; Poster #NR9-01):
- Vortioxetine 20 mg demonstrated significantly improved overall symptoms of MDD using the MADRS. Specifically, declines from baseline in MADRS total score ±standard error [SE] at week 8 were -12.83(±0.834), -14.30(±0.89), -15.57(±0.880), -16.90(±0.884), respectively for placebo (n=161), vortioxetine 20 mg (p=.023, n=147), and duloxetine 60 mg (p<.001, n=152) confirming assay sensitivity. Vortioxetine 15 mg did not meet statistical significance (p=NS, n=147).
- Adverse events (AEs) reported in ≥5% of the vortioxetine group were nausea, headache, dry mouth, dizziness, diarrhoea, constipation, vomiting, insomnia, fatigue, nasopharyngitis, and respiratory tract infection.
A Randomized, Double-blind, Placebo-controlled, Duloxetine-referenced Study of the Efficacy and Safety of Vortioxetine in Acute Treatment of MDD (Study 13267A conducted in Europe/South Africa; Poster #NR3-055):
- Both 15mg and 20mg doses of vortioxetine were statistically significantly superior to placebo in mean change from baseline in MADRS total score at Week 8, with a mean treatment difference to placebo (n=158) of -5.6 (vortioxetine 15mg, p<0.0001, n=148) and -7.1 points (vortioxetine 20mg, p<0.0001, n=151). Duloxetine (n=146) separated from placebo, confirming assay sensitivity.
- The most commonly reported AEs (≥5%) in the vortioxetine group were nausea, headache, diarrhoea, dry mouth, dizziness and hyperhidrosis.
A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Vortioxetine 10 mg and 20 mg in Adults with Major Depressive Disorder (Study 316; Poster #NR9-06):
- Vortioxetine 20mg significantly improved overall symptoms of MDD. Specifically, mean declines from baseline in MADRS total score at week 8 were -10.77 (± 0.807) (n=157) for placebo and -14.41 (±0.845) (p=0.002, n=150) for vortioxetine 20mg. Vortioxetine 10mg did not meet statistical difference (p=0.58, n=155).
- The most frequently reported AEs (≥5%) in the vortioxetine group were nausea, headache, diarrhoea, dizziness, constipation, vomiting, viral upper respiratory infection, and fatigue.
A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Two Doses of Vortioxetine in Adults with Major Depressive Disorder (Study 317; Poster #NR9-02):
- Vortioxetine 10mg and 15mg did not differ significantly in improvement of overall symptoms of MDD from placebo. Specifically, mean declines from baseline in MADRS total score ±standard error [SE] at week 8 were -12.87(±1.043), -13.66(±1.064), -13.36(±1.087), respectively, for placebo (n=160), vortioxetine 10mg (n=157) and vortioxetine 15mg (placebo=152).
- AEs reported by ≥5% in either vortioxetine group were nausea, headache, dry mouth, vomiting, constipation, diarrhoea, dizziness and flatulence.
The four pivotal studies presented during the meeting are part of a larger NDA data package that is currently under review by the US FDA that includes data from seven positive studies – six short-term studies and one long-term maintenance study – conducted in regions throughout the world. The vortioxetine global clinical program evaluated the effectiveness and safety profile of vortioxetine in a broad dose range of 5-20mg per day and included more than 7,500 total subjects.
