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AVP-786 Falls Short in Phase 3 Trial for Agitation in Alzheimer Patients
In a recent press release, Otsuka Pharmaceutical Co., Ltd. and its US subsidiaries, Otsuka Pharmaceutical Development & Commercialization, Inc., unveiled the topline results of the phase 3 clinical trial of AVP-786 in treating agitation associated with dementia due to Alzheimer disease. The trial (Trial 17-AVP-786-305; NCT03393520), failed to achieve statistical significance on its primary efficacy endpoint.
"The result of this trial is disappointing, but we plan to analyze the full dataset to determine the future potential of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer disease," said John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka, in the press release.
AVP-786, developed by Avanir Pharmaceuticals and acquired by Otsuka in December 2014, consists of 2 drugs: ultra-low dose quinidine, an inhibitor of the CYP2D6 enzyme, plus deuterium-modified dextromethorphan, which is an agonist of the NMDA receptor and the sigma-1 receptor as well as an inhibitor of the SERT and NET transporters.
Full results from the study are not yet available, but the company shared that the primary endpoint, which measured the mean change from baseline to week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) total score, did not show a significant difference between AVP-786 and placebo.
Moreover, the trial revealed a notable adverse event—the incidence rate of falls was higher in patients treated with AVP-786 compared to placebo, with 8.6% in the high dose group, 9.1% in the low dose group, and 2.8% in the placebo group. Additionally, 4 deaths were reported during the trial: 1 In the AVP-786 low dose group and 3 in the placebo group.
>>Related: FDA Approves First Pharmacological Treatment for Dementia-Related Agitation
Despite these setbacks, Otsuka said it remains committed to evaluating the full dataset to discern AVP-786's potential in treating agitation associated with dementia due to Alzheimer disease. This disease state can be identified by the following symptoms: pacing, gesturing, profanity, and aggression. These symptoms can severely impact the patient’s quality of life and often lead to nursing home admission.
"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," said Dr Kraus. "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."
In May of 2023, the US Food and Drug Administration (FDA) approved the expanded use of Otsuka’s Rexulti (brexpiprazole) for the treatment of agitation associated with dementia due to Alzheimer disease. Rexulti was developed in collaboration with Lundbeck Inc.
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