• The combination treatment arm of brexpiprazole and sertraline demonstrated improvement in symptoms of PTSD versus placebo (p<0.01) on the primary efficacy endpoint

• The efficacy of the combination arm over placebo was also supported by data from multiple secondary endpoints

• The companies will discuss the results with the FDA at an end-of-phase-II meeting in 2019

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announced today the achievement of positive clinical results (in intention-to-treat population) as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score change from baseline compared to placebo, when brexpiprazole and sertraline was given as combination treatment (p<0.01).

The treatment effects of brexpiprazole alone did not demonstrate clinically meaningful differences in comparison to placebo on the primary endpoint (p>0.35). The treatment effects of sertraline alone also did not to demonstrate clinically meaningful differences in comparison to placebo on the primary endpoint (p > 0.60).

The randomized, double-blind, placebo-and active-controlled phase II trial was initiated in 2017 and was designed to assess the efficacy, safety and tolerability of flexible doses of brexpiprazole as monotherapy, flexible doses of sertraline as monotherapy or as combination therapy with both brexpiprazole and sertraline in adult subjects with PTSD. The study consisted of a 12-week, double-blind treatment period, including a 1-week placebo run-in period, and a 14-day follow-up after the last dose. A total of 321 participants were randomized to treatment in the study.

The overall safety and tolerability of brexpiprazole were good (and comparable to previous data), when administered as either a combination of brexpiprazole and sertraline or brexpiprazole alone. One (1) incident of death was reported in the placebo group.

The companies plan to meet with the U.S. Food and Drug Administration (FDA) to discuss the results of the phase II study and to evaluate the continuation of a trial program.

About PTSD

PTSD is a psychiatric disorder that can develop as a response to traumatic events such as interpersonal violence, combat, life-threatening accidents or natural disasters. Core features of PTSD include a variety of symptoms, such as re-experiencing phenomena (i.e., flashbacks and nightmares), avoidance behavior, numbing (i.e., amnesia, anhedonia, withdrawal, negativism) and increased arousal (i.e., insomnia, irritability, poor concentration, hypervigilance. Psychiatric co-morbidities are common, and PTSD sufferers can also present with substance abuse, mood and other anxiety disorders, impulsive and dangerous behavior and self-harm.

Across different populations and countries, differences in PTSD prevalence (0.2-4%) can be attributed to geographically specific distributions of trauma type and severity, as well as cross-national and cultural differences in reporting or experiencing PTSD symptoms.

About brexpiprazole

Brexpiprazole was approved by the U.S. Food and Drug Administration in July 2015 to treat patients with schizophrenia and as an adjunctive treatment for patients with major depressive disorder (MDD). Brexpiprazole was also approved in 2017 by Health Canada and by the EMA in 2018 in Europe for the treatment of schizophrenia. In addition, brexpiprazole has been approved in several other countries across the world. Brexpiprazole is distributed and marketed under the brand name Rexulti^®. In Europe, brexpiprazole is distributed and marketed under the brand name Rxulti^®.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT_1A and dopamine D₂ receptors, and antagonist activity at serotonin 5-HT_2A receptors. Brexpiprazole exhibits high affinity (sub-nanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors.