Otsuka Reports AVP-786 Phase 3 Findings for Alzheimer's-Related Agitation

Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and its parent company, Otsuka Pharmaceutical Co., Ltd., have announced the findings from a phase 3 clinical trial for AVP-786, a treatment for agitation in patients with dementia caused by Alzheimer's disease. The trial, identified as 17-AVP-786-305 and registered as NCT03393520, did not yield a statistically significant result in the primary efficacy endpoint, which was the mean change in the Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline to week 12 when comparing AVP-786 to a placebo.
Despite the primary outcome, a safety concern was noted with a higher incidence rate of falls in patients treated with AVP-786 compared to those on a placebo. The adverse event was observed in 8.6% of patients on a high dose of AVP-786, 9.1% on a low dose, and 2.8% on a placebo. Additionally, there were four reported deaths during the trial; one in the low dose AVP-786 group and three in the placebo group.
The complete data from the study are not yet available, and further analysis is planned to assess the potential benefits of AVP-786 fully. Otsuka is committed to submitting the results for publication once the data are thoroughly evaluated.
John Kraus, M.D., Ph.D., the executive vice president and chief medical officer at Otsuka, expressed disappointment with the trial's outcome but emphasized the company's dedication to analyzing the data and continuing to innovate in the treatment of dementia-related agitation. He also highlighted Otsuka's pioneering achievement in 2023 with the approval of a drug for this patient demographic.
Agitation associated with Alzheimer's dementia is a prevalent neuropsychiatric symptom that significantly impacts the quality of life for patients and their caregivers. It encompasses a range of behaviors and is a predictor of nursing home admissions.
AVP-786 is a novel combination therapy consisting of deudextromethorphan hydrobromide (d6-DM) and quinidine sulfate (Q), with the latter acting as a CYP2D6 inhibitor. The deuteration of d6-DM enhances bioavailability by reducing its metabolism by the CYP2D6 enzyme.
Otsuka Pharmaceutical Co., Ltd. is a leading global healthcare company with a mission to improve health worldwide. The company is at the forefront of developing pharmaceuticals for mental, renal, and cardiovascular health and is also engaged in research on oncology and diseases like tuberculosis. Otsuka's presence in the U.S. began in 1973, and its U.S. affiliates, OPDC and Otsuka America Pharmaceutical, Inc. (OAPI), focus on developing and commercializing medicines for mental health and nephrology, employing 2,000 people in the country. The Otsuka group, with 47,000 employees globally, had sales of around USD 13.1 billion in 2022. The company is known for taking unconventional paths in its pursuit of innovation.