Latest Developments in Alzheimer's Drug Research: Tau Targets and Beyond

Pharmaceutical companies continue to pursue innovative approaches in the fight against Alzheimer's disease, with recent clinical trial results shaping the direction of future research. While some traditional targets face setbacks, new pathways emerge, offering hope for patients and researchers alike.

Tau-Targeting Therapies: Mixed Results and Continued Optimism

The pharmaceutical industry has seen a series of disappointments in tau-targeting Alzheimer's therapies, with Johnson & Johnson's posdinemab becoming the latest casualty. The drug failed to slow clinical decline in patients with Alzheimer's disease, joining a list of unsuccessful anti-tau candidates including UCB's bepranemab and Eli Lilly's LY3372689.

Despite these setbacks, some companies remain committed to the tau approach. Eisai, in collaboration with University College London, is developing etalanetug, which targets specific regions within the tau microtubule binding region (MTBR). Eisai's Chief Clinical Officer, Lynn Kramer, expressed confidence in the drug's potential, citing its unique tau-specific target.

"We've never expected them to succeed because if you don't have the right target you can't succeed," Kramer said, referring to failed anti-tau candidates. Eisai presented Phase Ib/II data at the Clinical Trials on Alzheimer's Disease (CTAD) 2025 conference, showing that etalanetug reduced all measurable forms of MTBR-tau243 in cerebrospinal fluid and plasma of patients with mild-to-moderate Alzheimer's.

Other companies, including Bristol Myers Squibb and Merck, are also pursuing tau-targeting treatments. BMS's BMS-986446 binds to different regions within the MTBR, while Merck's MK-2214, which targets phosphorylated serine 413 (pS413) tau, recently received FDA fast track designation.

Shifting Focus: Inflammation and Novel Targets

As tau-targeting therapies face challenges, the field is witnessing a shift towards other potential mechanisms. Howard Fillit, co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation, highlighted inflammation as a promising target.

"My personal view is that inflammation is a very important target in this illness, both systemic and neuroinflammation," Fillit stated. However, this approach has also seen its first setback, with Novo Nordisk's semaglutide failing to reduce Alzheimer's disease progression in recent trials.

Despite this, over 30 active clinical trials are exploring anti-inflammatory targets for Alzheimer's. Companies like Coya Therapeutics are investigating regulatory T cell (Treg)-targeted therapies, while Therini Bio is focusing on vascular dysfunction to treat the disease.

The landscape of Alzheimer's research is evolving rapidly. Fillit noted that while five years ago, 70% of clinical trials targeted amyloid and tau, today 70%-75% of targets are novel, with inflammation being the primary focus.

Amidst this shift, traditional targets still garner attention. Eli Lilly presented new data on trontinemab, its next-generation bispecific 2+1 amyloid-beta antibody, at CTAD 2025. The Phase I/II study showed potential effects on tau protein accumulation in the brain, despite not directly targeting tau.

As the field continues to evolve, researchers remain optimistic about the future of Alzheimer's treatment. "Forty years of research is finally paying off," Fillit concluded, reflecting on the breakthroughs and multiple pathways being explored in Phase II and III trials.