Avanir Pharmaceuticals, Inc. Reports Data from the Second Phase 3 Study Evaluating Investigational AVP-786 for the Treatment of Moderate-to-Severe Agitation in Patients with Alzheimer’s Dementia

Aliso Viejo, CA – September 27, 2019 – Avanir Pharmaceuticals, Inc., a pharmaceutical company committed to delivering innovative central nervous system (CNS) solutions to improve the lives of patients and their care communities, announced today that the second study of the company’s phase 3 clinical development program investigating the efficacy, safety and tolerability of AVP-786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) for the treatment of moderate-to-severe agitation in patients with Alzheimer’s dementia did not meet its primary and key secondary endpoints. Patients treated with AVP-786 did not experience a statistically significant improvement in agitation compared to patients treated with placebo, as measured by the Cohen-Mansfield Agitation Inventory (CMAI).

The most common adverse events in patients receiving AVP-786 versus placebo (greater than 5% incidence in either of the two doses of AVP-786) were falls, urinary tract infection, and somnolence. No deaths were considered related to treatment.

“Avanir is disappointed that this study did not meet its endpoints. There is a significant unmet medical need for treating agitation in patients with Alzheimer’s dementia, as currently there are no FDA-approved treatments,” said Sanjay Dubé, MD, Vice President, Research & Development, Head of Clinical Development & Scientific Strategy, Avanir Pharmaceuticals, Inc.

“We want to take this opportunity to express our sincere gratitude to the many patients, caregivers, investigators, and study teams who have participated in this clinical program,” said Wa’el Hashad, President and Chief Executive Officer, Avanir Pharmaceuticals, Inc. “We will continue to analyze the full set of data from the first two studies of the company’s phase 3 clinical development program, and explore the best path forward.”

There will be an estimated 5.8 million people in the United States with Alzheimer’s dementia by 2020, and this number is expected to reach 13.8 million by the year 2050i. Over the course of the disease, many patients with Alzheimer’s dementia will likely experience agitationii, which is characterized by excessive motor activity, verbal aggression and physical aggression that causes emotional distress to the patientsiii. Symptoms of agitation place a serious burden on the individuals with Alzheimer’s dementia and their caregivers, significantly affecting their health-related quality of life for all concernediv. Agitation has also been associated with increased risk of institutionalization and earlier progression to severe dementiav, vi, vii.

About AVP-786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q])
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 of d6-DM. AVP-786 is being studied in a phase 3 clinical development program as a candidate for moderate-to-severe agitation in patients with Alzheimer’s dementia. AVP-786 is also being investigated in patients with negative symptoms of schizophrenia, neuro-behavioral disinhibition in traumatic brain injury and intermittent explosive disorder.

About the Phase 3 Clinical Development Program
This study (15-AVP-786-302) was a 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel design. The study enrolled 522 U.S. and Canadian patients aged 50-90 with moderate-to-severe agitation and probable Alzheimer’s dementia. Patients living in either community settings or institutional care settings were included in the study. Patients were randomized to two doses of AVP-786 or placebo for 12 weeks. There is one additional ongoing phase 3 study (17-AVP-786-305) that also uses a parallel-group, placebo-controlled design. Avanir previously disclosed topline results of the first phase 3 study (15-AVP-786-301), which used Sequential Parallel Comparison Design (SPCD).

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. As part of our commitment, we have extensively invested in our pipeline and are dedicated to advancing CNS treatments in areas of high unmet medical need. For more information about Avanir, please visit http://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.”

Otsuka researches, develops, manufactures and markets innovative and original pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and also has research programs 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 Pharmaceutical and its related companies employ approximately 31,000 people worldwide. You can visit the company’s global website at https://www.otsuka.co.jp/en.

For additional information, please contact:
Corporate Communications, Avanir Pharmaceuticals, Inc.
T: 949-389-6738
E: mediarelations@avanir.com

iHebert L, et al. “Alzheimer disease in the United States (2010-2050), estimated using the 2010 census.” Neurology, 80(19): 1778–1783. 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719424/

iiAlzheimer’s Association. “2017 Alzheimer’s Disease Facts and Figures.” Alzheimer’s & Dementia, 13: 325-373. April 2017. https://www.sciencedirect.com/science/article/pii/S1552526017300511?viewFullText=true

iiiCummings J, et al. “Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition.” International Psychogeriatrics, 27:1, 7–17. 2015. https://www.ncbi.nlm.nih.gov/pubmed/25311499

ivLaybourne A, et al. “Carer coping and resident agitation as predictors of quality of life in care home residents living with dementia: Managing Agitation and Raising Quality of Life (MARQUE) English national care home prospective cohort study.” International Journal Of Geriatric. Psychiatry, 34:106-113. 2018. https://www.ncbi.nlm.nih.gov/pubmed/30276865

vKnapp M, et al. “Predictors of care home and hospital admissions and their costs for older people with Alzheimer’s disease: findings from a large London case register.” BMJ Open, 6:11, 1-15. 2016. https://bmjopen.bmj.com/content/bmjopen/6/11/e013591.full.pdf

viRabins P, et al. “Neuropsychiatric symptoms at baseline predict shorter time to severe dementia in a population-based sample of incident Alzheimer's disease: The Cache County dementia progression study.” Alzheimer's and Dementia, supplement, 8.4: 126-127. 2012. https://www.alzheimersanddementia.com/article/S1552-5260(12)00465-7/abstract

viiPeters M, et al. “Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: The Cache County Dementia Progression Study.”172(5): 460-5. 2015. https://www.ncbi.nlm.nih.gov/pubmed/25585033.