In the field of Alzheimer’s disease research, therapies targeting the tau protein have struggled to deliver positive clinical results. Johnson & Johnson is the latest company to experience a setback, as its anti-tau candidate posdinemab failed in mid-stage trials. This follows recent disappointments for other pharmaceutical companies: UCB’s bepranemab did not improve cognitive outcomes in Phase II trials last November, and Eli Lilly’s anti-tau drug LY3372689 was unsuccessful earlier this year.
Despite these challenges, Eisai remains confident in its own anti-tau approach. Chief Clinical Officer Lynn Kramer shared his perspective ahead of the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) conference. “We’ve never expected them to succeed because if you don’t have the right target you can’t succeed,” he said, referencing competitors’ setbacks.
Kramer explained that successful intervention depends on targeting a specific region of the tau protein involved in propagating disease within the brain. He noted that Johnson & Johnson’s therapy does not address this crucial seeding region. Eisai’s candidate, etalanetug, developed with University College London, is designed to bind specifically to the R2-R4 regions within tau’s microtubule binding region (MTBR). Data presented at CTAD showed reductions in MTBR-tau243—a marker associated with Alzheimer’s pathology—in both cerebrospinal fluid and plasma among seven patients treated with etalanetug.
According to Kramer, etalanetug aims to prevent the “spreading phenomenon” unique to Alzheimer’s by blocking tau at its seed location. “[In] almost all tauopathies, tau builds up in the neuron,” he said. “It doesn’t spread across to the next like an infection.”
Other pharmaceutical companies are also continuing their work on anti-tau therapies despite recent failures. Bristol Myers Squibb is advancing BMS-986446, which binds different regions of tau within MTBR, while Merck recently received FDA fast track designation for MK-2214 targeting phosphorylated serine 413 (pS413) tau.
Kramer emphasized that tau may be a better indicator of cognitive decline than amyloid because it accumulates over time; amyloid levels appear similar regardless of cognitive status according to Leqembi’s AHEAD 3-45 and CLARITY-AD trials.
However, some experts urge caution regarding expectations for anti-tau drugs. Howard Fillit, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), told BioSpace: “It’s still probably a bit early days with anti-tau and anti-tangle therapies.” He pointed out that much current data comes from animal studies rather than human trials.
Research into other treatment strategies continues as well. Fillit highlighted inflammation as an important emerging target for Alzheimer’s interventions: “My personal view is that inflammation is a very important target in this illness, both systemic and neuroinflammation.” While Novo Nordisk's semaglutide did not reduce disease progression in recent trials focused on inflammation pathways, there are currently more than 30 ongoing clinical trials exploring anti-inflammatory targets for Alzheimer’s therapy. ADDF has invested in several such companies—including Coya Therapeutics—developing regulatory T cell-targeted treatments being tested for multiple neurodegenerative diseases.
Therini Bio is taking a different approach by focusing on vascular dysfunction linked to neuroinflammation; its lead candidate THN391 aims to inhibit harmful inflammatory responses triggered by fibrin deposits outside blood vessels.
Fillit observed a shift away from traditional targets such as amyloid and tau toward novel approaches—now comprising roughly three-quarters of all clinical trial targets compared with just 30% five years ago—with inflammation receiving particular attention.
Traditional targets still attract interest; Roche presented new Phase I/II data at CTAD for trontinemab—a bispecific antibody against amyloid-beta—that also appeared to affect brain accumulation of tau protein according to biomarker analysis.
Reflecting on progress seen at CTAD 2025, Fillit stated: “Very exciting, because we really have breakthroughs and multiple pathways and a lot of drugs in Phase II and even a number in Phase III. Forty years of research is finally paying off.”
