Alzheimer's drug pipeline broadens beyond amyloid as researchers pursue new targets

The Alzheimer's disease drug pipeline has reached record size and diversity, with researchers increasingly moving beyond the amyloid-plaque approach that has dominated the field for decades in favor of treatments targeting inflammation, immune processes, neurotransmitters and tau protein.

According to a new review, Alzheimer's Disease Drug Development Pipeline: 2026, drug developers are advancing 158 compounds across 192 clinical trials, with 73% of investigational drugs pursuing disease-modifying strategies rather than symptom management alone.

Anti-amyloid therapies — which yielded the two FDA-approved Alzheimer's treatments, Eli Lilly's (LLY) Kisunla and Eisai (ESAIY) and Biogen's (BIIB) Leqembi — now account for just 16% of the pipeline, down from 33% a decade ago. The decline reflects years of industry setbacks as drugs targeting the protein failed to deliver the transformative outcomes researchers had anticipated. Roche (RHHBY) is among those still pursuing the approach, using so-called brain shuttle technology designed to ferry therapies across the blood-brain barrier.

Drugs targeting neurotransmitter receptors have emerged as the pipeline's largest category, comprising 24% of 2026 trials. That group includes repurposed compounds such as Bristol Myers Squibb's (BMY) schizophrenia drug Cobenfy, which is being studied for Alzheimer's-related psychosis. Inflammation and immune-targeting therapies account for 18% of the pipeline, while tau-focused treatments represent 9%.

Merck & Co. (MRK) is testing a Phase 2 tau-targeting antibody, MK-2214, while Biogen recently reported positive Phase 2 results for its tau candidate BIIB080, which the company said would advance to registrational development. South Korean biotech AriBio is pursuing a multi-mechanism approach with AR1001, a small molecule targeting both neuroinflammation and tau pathology, and recently licensed the drug to Shanghai Fosun Pharmaceutical Group.

More than a third of the overall pipeline consists of repurposed drugs, including the diabetes medication metformin, reflecting efforts to accelerate development timelines and reduce costs.

The field is also shifting toward greater use of biomarkers, with more than half of ongoing trials using them to guide patient enrollment and 27% incorporating them as a primary outcome measure.

Several key trials are expected to read out this year, including AriBio's Phase 3 study of AR1001 and trials of repurposed symptom-targeting compounds.

"While the current FDA-approved treatments for early Alzheimer's are a game-changing breakthrough, there is still a great unmet need for drug development to address the needs of the growing population of individuals with Alzheimer's in all communities and across all stages of the disease," said Maria Carrillo, chief science officer at the Alzheimer's Association.