Otsuka Halts Alzheimer’s Agitation Drug After Phase III Failure

Otsuka Pharmaceuticals has announced its decision to halt the development of its drug candidate for Alzheimer’s-related agitation after it failed to show efficacy in a critical late-stage trial. The drug, known as AVP-786, did not demonstrate any significant improvement over a placebo in the Cohen-Mansfield Agitation Inventory (CMAI) total score, which measures agitation in patients with Alzheimer’s disease (AD).

The pharmaceutical company had acquired AVP-786 through its $3.5 billion acquisition of Avanir Pharmaceuticals in late 2014. The drug is a combination of ultra-low dose quinidine and deuterium-modified dextromethorphan, designed to enhance bioavailability and reduce susceptibility to metabolism. While previously tested by Avanir for major depressive disorder, Otsuka focused its efforts on assessing the drug solely for agitation linked to AD.

Otsuka already has a presence in the market for this indication. In collaboration with Lundbeck, the company offers Rexulti (brexpiprazole), initially approved for schizophrenia and as an adjunct therapy for major depressive disorder (MDD). In May 2023, Rexulti gained approval for treating agitation associated with dementia due to Alzheimer’s, marking it as the first drug for this specific condition. This new indication has fueled increased sales, with Lundbeck reporting an 18.8% monthly growth in demand.

However, the market for treating AD-related agitation is becoming increasingly competitive. In April 2024, IGC Pharma revealed interim results from its Phase II trial featuring a THC-based formulation, which showed a notable reduction in agitation by the second week compared to a placebo. This Maryland-based company is pioneering the use of THC in AD agitation.

Axsome Therapeutics is also making strides in this area with its drug AXS-05, currently undergoing a Phase III trial. The trial's completion is expected in the first half of 2024, and the company plans to seek regulatory approval following the study, having previously received feedback from the FDA to provide long-term safety data.

Alzheimer’s disease affects an estimated 6.9 million people in the United States, with approximately 76% of these patients experiencing agitation. Such symptoms include pacing, restlessness, and both verbal and physical aggression, which significantly strain caregivers.

This development highlights the ongoing challenges in finding effective treatments for AD-related agitation. Despite the setback with AVP-786, the pharmaceutical landscape continues to evolve with new therapies and research that aim to alleviate the burden of this condition.