Quinidine Sulfate

PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)-- Otsuka Pharmaceutical Development & Commercialization, Inc., (OPDC) and our parent company Otsuka Pharmaceutical, Co. Ltd. (Otsuka) announce topline results of the phase 3 clinical trial of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer’s disease (Trial 17-AVP-786-305; NCT03393520). A statistically significant difference was not achieved on the primary efficacy endpoint, mean change from baseline to week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) total score between AVP-786 and placebo. There was one treatment-emergent adverse event, a fall, that appeared with an incidence rate of more than 5% in patients treated with AVP-786 and greater than placebo; 16 (8.6%) in AVP-786 high dose, 18 (9.1%) in AVP-786 low dose and 6 (2.8%) placebo. There were 4 deaths reported in the trial; 1 (0.5%) in the AVP-786 low dose group and 3 (1.4%) in the placebo group. Full study results are not yet available. Further prespecified and exploratory analyses of the data set will be conducted to determine the full potential of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer’s disease. Otsuka intends to submit the trial results for scientific publication at a later date. “While the result of this trial is disappointing, we plan to analyze the full data set to determine the future potential of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer’s disease. In 2023, Otsuka became the first company to get a drug approved for this patient population and we are committed to expanding and innovating in this area,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. “We are deeply grateful to all of the study participants, their caregivers, and the investigators who took part in this trial and contributed to this research.” 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.1,2 Agitation associated with dementia due to Alzheimer’s disease covers a large group of behaviors such as pacing, gesturing, profanity, shouting, shoving, and hitting.3 Symptoms of this condition are also a consistent predictor of nursing home admission. 4,5,6 About AVP-786 AVP-786 is a combination of deudextromethorphan hydrobromide (d6-DM) and quinidine sulfate (Q), a CYP2D6 inhibitor. Deuteration was observed to significantly reduce susceptibility to cytochrome P450 (CYP2D6) enzyme metabolism thereby increasing the bioavailability. 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 and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at REFERENCES 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 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 3 Cummings J et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr 2015; 27: 7–17 4 Gaugler JE et al. Predictors of nursing home admission for persons with dementia. Med Care 2009; 47: 191–198 5 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 6 Yaffe K et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002;287:2090 -2097

Otsuka America Pharmaceutical, Inc. (OAPI), announces that it will integrate Avanir Pharmaceuticals into its business as of January 1, 2023. The move brings together the knowledge, capabilities and best practices of both companies to further advance solutions to treat central nervous system (CNS) disorders. Avanir and OAPI are both subsidiaries of OAI, a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd., a global healthcare company. "I'm extremely proud to have led this extraordinary team of dedicated employees over the past five years," said Wa'el Hashad, president and chief executive officer, Avanir Pharmaceuticals. "Avanir's spirit of innovation and excellence will live on at Otsuka and ensure the continued innovation that will bring hope to patients and families." "Avanir and Otsuka have always shared a deep commitment to advancing solutions that improve the lives of patients and their caregivers. We welcome every new employee to the Otsuka family and know each will continue to make an impact on the communities we serve," said Tarek Rabah, president and CEO, Otsuka North America Pharmaceutical Business (OAPI). "This integration will bring greater opportunities to develop treatments for those impacted by CNS disorders." Founded in 1988 as Lidak Pharmaceuticals, the company became Avanir Pharmaceuticals in 1998 and launched their flagship product, Nuedexta (dextromethorphan hydrobromide and quinidine sulfate). Acquired by Otsuka in 2015, Avanir has been at the forefront of developing and delivering groundbreaking pharmaceutical treatments for people with CNS conditions. About Avanir Pharmaceuticals, Inc. Avanir Pharmaceuticals, Inc. is a pharmaceutical company committed to delivering innovative central nervous system (CNS) solutions to improve the lives of patients and their care communities. For more information about Avanir, visit https://www.avanir.com. Avanir is a subsidiary of Otsuka America, Inc. (OAI), a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd., a global healthcare company with the corporate philosophy, "Otsuka-people creating new products for better health worldwide."