Alzheimer's Treatment Landscape Evolves: Industry Shifts Focus to Holistic Approaches

The pharmaceutical industry is witnessing a significant shift in its approach to Alzheimer's disease treatment, with companies increasingly focusing on holistic strategies that address both the underlying causes and the symptoms of the condition. This trend comes in the wake of recent approvals for disease-modifying drugs and acknowledges the limitations of these treatments.

Disease-Modifying Therapies Make Progress, But Challenges Remain

The approvals of Biogen and Eisai's Leqembi in 2023 and Eli Lilly's Kisunla in 2024 marked a milestone in Alzheimer's treatment as the first disease-modifying therapies. These anti-amyloid antibodies have generated new momentum in the field, with M&A deal values in the Alzheimer's space surging from $2 billion in 2022 to $18 billion in 2023.

However, these treatments face significant limitations. They are approved only for patients with mild-to-moderate Alzheimer's disease and have shown limited efficacy. Concerns over amyloid-related imaging abnormalities (ARIA) have also plagued these drugs. In response, Eli Lilly recently secured a label update for Kisunla, introducing a gradually increasing dosing schedule that has been shown to decrease the incidence of ARIA-E (brain swelling).

Despite these challenges, research into disease-modifying treatments continues. Bristol Myers Squibb (BMS) is conducting a Phase II trial targeting tau pathology, which Ken Rhodes, Vice President of Neuroscience Research at BMS, describes as "the other major pathology of Alzheimer's disease" beyond amyloid beta. Meanwhile, Eli Lilly's Phase III TRAILBLAZER-ALZ 3 trial in presymptomatic Alzheimer's is eagerly anticipated, with results expected in November 2027.

Renewed Focus on Symptomatic Treatments

Acknowledging the limitations of disease-modifying drugs, pharmaceutical companies are renewing efforts to develop treatments that address the devastating symptoms of Alzheimer's. This approach aims to improve patients' quality of life by targeting cognitive impairment, psychosis, and agitation associated with the disease.

BMS's Cobenfy, originally developed by Eli Lilly as an Alzheimer's treatment before being approved for schizophrenia, is now being tested in the Phase III ADEPT-2 study for Alzheimer's-related psychosis. Results are expected by the end of this year. BMS is also developing an eIF2B activator to treat cognitive impairment and an FAAH/MAGL dual inhibitor for Alzheimer's disease agitation.

Acadia Pharmaceuticals is testing ACP-204, an inverse agonist of the 5-HT2A receptor, in a Phase II trial for Alzheimer's disease psychosis. Catherine Owen Adams, CEO of Acadia, emphasized the importance of addressing symptoms, stating, "With so many patients worldwide affected by Alzheimer's, I think the time is now to start at least alleviating some of these symptoms."

In 2023, Otsuka and Lundbeck received FDA approval for Rexulti as the first treatment for agitation in Alzheimer's disease. However, the drug carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis, highlighting the ongoing challenges in developing safe and effective treatments for this population.

As the Alzheimer's treatment landscape continues to evolve, the industry's focus on both disease-modifying and symptomatic approaches reflects a growing recognition of the need for a comprehensive strategy to combat this complex and devastating disease. With over 55 million people living with dementia globally and that number expected to reach 78 million by 2030, the urgency for effective treatments has never been greater.