H Lundbeck A/S has reported positive results for the REVIVE study, a double-blind randomized study of Brintellix (vortioxetine) versus agomelatine in adults with major depression (MDD) who changed antidepressant treatment after an inadequate response to SSRI or SNRI treatment. The objective was to compare the efficacy and tolerability of flexible dose treatment with Brintellix (10-20mg/day) versus agomelatine (25-50 mg/day) in this challenging MDD patient population.
The study was conducted in Europe and one of the newest antidepressants agomelatine was chosen as a comparator because of its different mode of action from conventional SSRI/SNRI therapies.
Few randomized, double-blind studies comparing treatment strategies in MDD patients who were unresponsive to first-line antidepressant treatment have been conducted. This is one of these few studies which also shows a significant difference between treatments.
Anders Gersel Pedersen, executive vice president and head of Research & Development at Lundbeck, said, “Patients with inadequate response to current SSRI or SNRI therapies represent a large proportion of patients suffering from major depression. Only a few years ago, the landmark STAR*D study1 confirmed a significant unmet medical need as only half of patients responded to their first-line treatment, which was an SSRI. First-line treatments in clinical practice are typically SSRIs or SNRIs.”
In the REVIVE study, the primary efficacy endpoint was change from baseline to week 8 in MADRS total score. Secondary endpoints included assessments of anxiety symptoms (HAM-A), global clinical judgment (CGI-S, CGI-I) and overall functioning (SDS). Patients were randomized to Brintellix (10-20 mg/day) or agomelatine (25-50 mg/day) for 12 week of double-blind treatment.
On the primary efficacy endpoint, Brintellix (n=252) was statistically significantly superior to agomelatine (n=241) (p<0.05) by 2.2 MADRS points. Significant differences in favor of Brintellix were also found for MADRS, HAM-A, CGI-S, CGI-I and SDS from week 4 onwards (p<0.05). Brintellix was well tolerated, with fewer patient withdrawals in the Brintellix group (5.9 per cent) vs. Agomelatine (9.5 per cent). Adverse events were consistent with results from previous clinical phase III studies and included nausea (Brintellix 16 per cent and agomelatine nine per cent) (incidence >five per cent and higher than agomelatine). Overall, this study confirms that Brintellix is efficacious and well tolerated.
Separately, Lundbeck plans to present further efficacy and safety data from its pivotal clinical programme at the 166th American Psychiatric Association (APA) Annual Meeting in San Francisco, USA, which will be held from May 18 to 22, 2013.
Brintellix is under investigation as a multimodal antidepressant that is thought to work through a combination of two complementary mechanisms of action: receptor activity modulation and reuptake inhibition. In vitro studies indicate that Brintellix is a 5-HT3,5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the serotonin transporter (SERT). In vivo non-clinical studies have demonstrated that Brintellix modulates neuronal firing and neurotransmitter release in multiple systems, resulting in enhanced levels of serotonin, noradrenaline, dopamine, acetylcholine and histamine in specific areas of the brain.
The multimodal activity profile of Brintellix is different from the profile of currently anti-depressive medicines.
In 2012, Lundbeck filed Brintellix (formerly described as Lu AA21004) for regulatory approval for the indication of MDD in the EU, Canada and other markets, as well as in the US with its co-development partner, Takeda.
MDD - commonly referred to as major depression — is a highly prevalent, serious and debilitating medical condition. The disease can be described as a complex syndrome of emotional, cognitive and somatic symptoms. MDD is the leading worldwide cause of years lost due to disability, and projected to be the biggest contributor to the worldwide burden of disease by 2030. It is estimated that between a quarter and a third of the population will develop at least one episode of major depression during their life-time and of these as many as two thirds will have recurrent episodes, and one third will develop a chronic condition.
Lundbeck is a global pharmaceutical company highly committed to improving the quality of life of people living with brain diseases.