SAN DIEGO, California - (August 4, 2022) - Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka) and H. Lundbeck A/S (Lundbeck) today presented positive results from a Phase 3 clinical trial of brexpiprazole in the treatment of agitation in patients with Alzheimer's dementia at the 2022 Alzheimer's Association International Conference.

The double-blind, randomized, placebo-controlled trial of 345 male and female participants with a diagnosis of probable Alzheimer's disease was designed to assess the safety, tolerability, and efficacy of two fixed doses of brexpiprazole (2 mg/day and 3 mg/day) in the treatment of patients with agitation in Alzheimer's dementia. All participants in the treatment group (N=228) and placebo group (N=117), aged 55-90 years (inclusive), met criteria of agitation as defined by the International Psychogeriatric Association.

The primary outcome was the change in the Cohen-Mansfield Agitation Inventory (CMAI) total score at week 12 for all patients treated with brexpiprazole versus those treated with placebo. The key secondary outcome was the change in the Clinical Global Impression - Severity of Illness (CGI-S) score, as related to symptoms of agitation.

In the study, the improvements from baseline on the primary endpoint of CMAI for patients receiving brexpiprazole 2 mg/day or 3 mg/day were statistically greater than for those receiving placebo (brexpiprazole = -22.6, placebo = -17.3; p=0.0026). This result was supported by a statistically superior improvement on the key secondary endpoint of CGI-S, as related to agitation (p=0.0055). When analyzed individually, both 2 mg and 3 mg doses showed statistically significant improvements vs. placebo on the CMAI. In the study, there were no adverse events with more than 5 percent incidence in all patients treated with brexpiprazole with an incidence greater than placebo; asthenia (extreme, chronic weakness and fatigue), diarrhea, somnolence, dizziness, urinary tract infections and nasopharyngitis occurred in more than 2 percent of brexpiprazole-treated patients with an incidence greater than placebo. In addition, adverse events such as falls, akathisia, and extrapyramidal disorder occurred at a rate of less than 2% in the patients treated with brexpiprazole. Discontinuations due to adverse events occurred in 5.3% of patients treated with brexpiprazole and 4.3% of patients receiving placebo.

"The positive results from this double-blind trial as well as two earlier trials, represent a potentially significant milestone in our effort to identify a first-of-its-kind treatment for this very prevalent and disruptive neuropsychiatric symptom that affects many patients with Alzheimer's dementia," said Robert McQuade, PhD, executive vice president, chief strategy officer and interim chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "We are one step closer to the possibility of bringing the first FDA-approved pharmacological treatment for agitation in Alzheimer's dementia to patients and their family members and caregivers."

The Supplemental New Drug Application (sNDA) will be comprised of this study as well as two earlier trials.1 In February 2016, the FDA granted fast track designation for brexpiprazole for treatment of agitation in patients with Alzheimer's dementia.

"We are incredibly grateful to all the patients with Alzheimer's dementia, their families and the investigators who participated in the trials and contributed greatly to this research," Dr. Johan Luthman, executive vice president and head of Research & Development at Lundbeck commented. "Researchers will continue to analyze the data set to determine the full potential of brexpiprazole in the treatment of agitation in patients with Alzheimer's dementia. Based on this outcome Otsuka and Lundbeck are planning a regulatory filing to the U. S. Food and Drug Administration later in 2022."