Otsuka Pharmaceutical Co., Ltd. 
H. Lundbeck A/S

April 17, 2023

Otsuka and Lundbeck Issue Statement on U.S. Food and Drug Administration (FDA)
Advisory Committee Meeting on brexpiprazole for the Treatment of
Agitation Associated with Alzheimer's Dementia

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announce the Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) met to discuss the supplemental New Drug Application (sNDA) of REXULTI® (brexpiprazole) for the treatment of agitation associated with Alzheimer's dementia (AAD). The committee voted 9-1 that Otsuka and Lundbeck provided sufficient data to allow the identification of a population in whom the benefits of treating AAD with brexpiprazole outweigh its risks.

If approved, brexpiprazole would be the first FDA-approved treatment indicated for AAD in the U.S. The FDA will consider the feedback from the committee as it reviews the sNDA for brexpiprazole in advance of the May 10 Prescription Drug User Fee Act (PDUFA) target action date.

"We are thankful to the FDA and committee members for the thoughtful review and discussion of brexpiprazole for the treatment of agitation associated with Alzheimer's dementia," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc. "We will continue to work closely with the FDA in advance of our scheduled PDUFA date and feel confident in the impact brexpiprazole could have in addressing the significant unmet need within the Alzheimer's community."

The sNDA included data from two positive clinical phase III studies that investigated the treatment of brexpiprazole in patients with AAD. Study 331-12-283 demonstrated brexpiprazole 2 mg/day was statistically superior to placebo for the primary endpoint of mean change in Cohen-Mansfield Agitation Inventory (CMAI) Total Score from baseline to Week 12 (p < 0.05). In Study 331-14-213, treatment with brexpiprazole 2 and 3 mg/day showed statistically significant improvement compared with placebo for the primary efficacy endpoint, the mean change in CMAI Total Score from baseline to Week 12 (p < 0.05).

"Agitation is one of the most complex and stressful aspects of care in patients affected by Alzheimer's dementia," said Johan Luthman, executive vice president, Lundbeck Research & Development. "With no FDA-approved products for AAD, there is an urgent need for a treatment that could lessen the neuropsychiatric symptoms that AAD patients and caregivers struggle with. Having an approved treatment option for AAD could provide hope to people impacted by this debilitating condition."