Amyloid is increasingly ceding ground in Alzheimer’s disease R&D to new approaches targeting inflammation, immune processes, neurotransmitters and tau.
In fact, the Alzheimer’s pipeline has never been larger or more varied, according to a new review article, Alzheimer’s Disease Drug Development Pipeline: 2026. Drug developers are now advancing 158 drugs across 192 trials and are increasingly relying on biomarkers to determine which patients to enroll and to gauge outcomes.
Notably, 73% of investigational drugs this year leverage disease-modifying strategies, although a smaller percentage of the pipeline is still focused on symptom management.
While most Alzheimer’s treatments in clinical trials are new, more than a third of the pipeline is made up of repurposed drugs like the diabetes treatment metformin and Bristol Myers Squibb’s schizophrenia therapy Cobenfy.
A diverse pipeline
The amyloid-plaque targeting approach has led to two FDA-approved Alzheimer’s drugs, Kisunla and Leqembi, and is far from dead. But drugs aimed at this toxic protein are on the decline.
Anti-amyloid medications now make up 16% of the pipeline, down from 33% a decade ago. This drop follows years of industry disappointment over drugs that haven’t delivered the game-changing results many researchers hoped for. Still, companies like Roche are attempting to realize their commercial potential with new delivery approaches such as their brain shuttle technology that moves the drugs past the stubborn blood-brain barrier.
Other strategies are now taking a bigger bite of the pipeline. Drugs targeting neurotransmitter receptors now comprise 24% of the 2026 pipeline, and include a number of repurposed drugs such as Cobenfy. Treatments aimed at inflammation or the immune system make up 18% of the pipeline while 9% target tau.
Therapies aimed at reducing inflammation hold promise because the process might be linked to why many with amyloid plaques never develop dementia. But it may be a challenge to tamp down inflammation without triggering serious side effects.
Like amyloid, tau tangles have also been linked to Alzheimer’s, making the protein another top target for drugmakers like Merck & Co., which is testing a phase 2 antibody called MK-2214. Biogen is also in the hunt for a tau-targeting treatment with BIIB080, recently releasing positive phase 2 data that will tee up “registrational development,” the company said.
Other companies are taking a multi-mechanism approach, including AriBio Co, which has an investigational disease modifying small molecule, AR1001, that targets neuroinflammation and tau pathology. The company recently optioned the drug to Shanghai Fosun Pharmaceutical Group.
The rise of biomarkers
Instead of the old symptom-based playbook, Alzheimer’s researchers are increasingly using biomarkers to find patients and track their progress. More than half of ongoing trials use a biomarker to guide patient enrollment, and 27% use one as a primary outcome measure, according to the report.
This year could prove pivotal in determining the trajectory of several approaches. Aria’s phase 3 for AR1001 is among the trials concluding this year alongside several studies of repurposed symptom-addressing drugs, including Cobenfy for Alzheimer’s psychosis and metformin.
The gaps that still exist in Alzheimer’s treatment remain significant.
“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,” Maria Carrillo, chief science officer and medical affairs lead at Alzheimer’s Association, said in a written release.
