Valby, Denmark, May 11, 2023 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical, Co. Ltd. (Otsuka) announce the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) of Rexulti® (brexpiprazole) for use in the treatment of agitation associated with dementia due to Alzheimer's disease.

This approval makes Rexulti the first and only pharmacological treatment approved in the U.S. for agitation associated with dementia due to Alzheimer's disease. Agitation is a common neuropsychiatric symptom in Alzheimer's dementia and one of the most complex and stressful aspects of caring for people living with the condition. It is reported in approximately half of people with Alzheimer's dementia and is associated with earlier nursing home placement[. ]Rexulti is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease.

Deborah Dunsire, CEO and president, Lundbeck, said, "This approval is a testament to our commitment and unwavering support of patients and caregivers to lessen the symptoms of agitation associated with dementia due to Alzheimer's disease. We look forward to offering this first FDA-approved treatment option to address this significant unmet need for patients. We are grateful to the patients and caregivers who participated in these important trials."

Makoto Inoue, president and representative director of Otsuka, commented, "Today marks a major milestone for patients, caregivers, and families navigating the complexities of agitation associated with dementia due to Alzheimer's disease. Otsuka Pharmaceutical will continue its efforts to engage and provide options for those impacted by this devastating condition."

The FDA previously granted priority review for the sNDA, a designation for a drug application that represents a significant improvement in the safety and/or effectiveness of the treatment, diagnosis, or prevention of a serious medical condition.

The submission was based on two phase III, 12-week, randomized, double-blind, placebo-controlled fixed-dose studies that evaluated the frequency of agitation symptoms in patients with dementia due to Alzheimer's disease based on the Cohen-Mansfield Agitation Inventory (CMAI) total score. The primary endpoint was a change in agitation symptom frequency (CMAI total score) from baseline at Week 12 in both studies. Brexpiprazole patients with agitation associated with dementia due to Alzheimer's disease achieved a 31% greater reduction from baseline in frequency of agitation symptoms vs. placebo.

Overall, the data showed brexpiprazole as being well-tolerated with a low incidence of discontinuations, and with a safety profile consistent with the known safety profile of brexpiprazole in other indications[3].

About agitation associated with dementia due to Alzheimer's disease

Agitation associated with dementia due to Alzheimer's disease is a common neuropsychiatric symptom that is reported in approximately half of all patients with Alzheimer's dementia. The condition has a large impact on the quality of life for the patients, family members, and caregivers[1,3].

Agitation associated with dementia covers a large group of behaviors occurring in patients with Alzheimer's disease, such as pacing, gesturing, profanity, shouting, shoving, and hitting[4]. Symptoms of agitation are also a consistent predictor of nursing home admission in patients with dementia, including those with Alzheimer's disease[5,6,7].

About Brexpiprazole

Brexpiprazole was approved in the U.S. in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively. It was approved by the Ministry of Health, Labour and Welfare in Japan and by the European Medicines Agency (EMA) in 2018 for the treatment of schizophrenia.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck.  The mechanism of action of brexpiprazole is unknown, however the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT\1A\ and dopamine D\2\ receptors and antagonist activity at serotonin 5-HT\2A\ receptors.[8]

Lundbeck contacts

Investors: Media:
                                   
Palle Holm Olesen Thomas Mikkel Mortensen
Vice President, Investor Relations Media Relations Lead, Corp. Communication
PALO@lundbeck.com THMR@lundbeck.com
+45 30 83 24 26 +45 30 83 30 24

Otsuka contacts

Otsuka in the U.S.

Robert Murphy

Corporate Communications

Otsuka America Pharmaceutical, Inc.

robert.murphy@otsuka-us.com

+1 609 249 7262

Otsuka outside the U.S.

Jeffrey Gilbert

Leader, Pharmaceutical PR 

Otsuka Pharmaceutical Co., Ltd.

Gilbert.jeffrey.a@otsuka.co.jp

About H. Lundbeck A/S

Lundbeck is a global pharmaceutical company specialized in brain diseases. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best. We are committed to fighting stigma and discrimination against people living with brain diseases and advocating for broader social acceptance of people with brain health conditions. Our research programs tackle some of the most complex challenges in neuroscience, and our pipeline is focused on bringing forward transformative treatments for brain diseases for which there are few, if any therapeutic options.

For additional information, we encourage you to visit our corporate site www.lundbeck.com and connect with us on Instagram (h_lundbeck), Twitter at @Lundbeck andvia LinkedIn. 

About Otsuka

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka-people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a "big venture" company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies' 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. 

OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.1 billion in 2022.

All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS.Otsuka Pharmaceutical Co., Ltd.'s global website is accessible at https://www.otsuka.co.jp/en/.

Citations:

1. Halpern R et al. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry 2019; 34: 420-431
2. Gaugler JE et al. Predictors of nursing home admission for persons with dementia. Med Care 2009; 47: 191-198
3. Fillit H et al. Impact of agitation in long-term care residents with dementia in the United States. Int J Geriatr Psychiatry 2021; 36: 1959-1969
4. Fillit H et al. Impact of agitation in long-term care residents with dementia in the United States. Int J Geriatr Psychiatry 2021; 36: 1959-1969
5. Cummings J et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr 2015; 27: 7-17
6. Gaugler JE et al. Predictors of nursing home admission for persons with dementia. Med Care 2009; 47: 191-198
7. Kales HC et al. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005;13:441-449
8. Yaffe K et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002;287:2090 -2097

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