FDA Breakthrough Therapy Designation for Two More Alzheimer’s Drugs Demonstrates Promise of Pipeline

This week, the FDA granted Breakthrough Therapy designation to two new Alzheimer’s drugs in development. According to the FDA, the designation is used to “expedite the development and review of drugs to treat a serious condition…where early evidence indicates the drug may demonstrate substantial improvement over available therapy.”

“This month’s approval of aducanumab was just the beginning,” said Howard Fillit, M.D., Founding Executive Director and Chief Science Officer at the Alzheimer’s Drug Discovery Foundation. “These FDA announcements demonstrate the depth and strength of the Alzheimer’s research pipeline and the expanding reliance on biomarkers in clinical trials.”

Like aducanumab, the two drugs that received breakthrough designation—lecanemab (Eisai and Biogen) and donanemab (Eli Lilly)—work by removing toxic amyloid deposits in the brain. Amyloid buildup is just one of many processes associated with the biology of aging that contribute to Alzheimer’s.

Reflecting the complexity of pathways that may all be tied to the disease, the Alzheimer’s Drug Discovery Foundation’s visionary approach to Alzheimer’s research features a diverse research pipeline that extends beyond a focus on just amyloid. More than half of the 120 drugs currently in clinical trials are focused on a wide range of drug targets.

In addition to drugs targeting misfolded proteins like amyloid and tau, the Alzheimer’s Drug Discovery Foundation’s clinical research portfolio includes drugs targeting inflammation, vascular problems, genetic alterations, and many other pathways that affect brain health. The robust Alzheimer’s research pipeline, complemented by a growing number of biomarkers, means that the clinical trials underway today are more rigorous and more promising than ever.

The Alzheimer’s Drug Discovery Foundation also commits millions of dollars annually to support the development of diagnostic biomarkers through its Diagnostics Accelerator. Among the successes resulting from ADDF’s early support are the Amyvid PET scan, which was used to identify patients for the aducanumab clinical trials, and PrecivityAD, a blood test that came to market in 2020.

Like Biogen’s phase 3 aducanumab studies, lecanemab and donanemab studies are using PET amyloid scans to track the drugs’ effect on amyloid in the brain. But the two newer trials are also adding a more recently validated biomarker, the tau PET scan, to track reduction in toxic tau protein. Amyloid plaques and tau tangles are the primary markers of Alzheimer’s disease.

“Biomarkers are giving researchers the ability to design more rigorous trials that are sure to enroll patients most likely to benefit from the therapy — namely, those who have the pathology that the test drug targets,” said Dr. Fillit. “This is why our Diagnostics Accelerator is so committed to supporting research to ensure that every potential drug target for this complex disease has corresponding biomarkers.”

The ADDF is strongly encouraged by this week’s news that adds to the growing body of recognition of the critical value of biomarkers in Alzheimer’s research, as well as the FDA’s willingness to expedite review of potential treatments for this devastating disease.