The drug development for Alzheimer's disease (AD), which is considered a "research and development black hole," is accelerating, and another A β drug is about to be approved.
On June 10th local time, the results of a meeting held by the Peripheral and Central Nervous System Drug Advisory Committee of the US Food and Drug Administration (FDA) regarding the licensing application of Donanemab for the treatment of early-stage symptomatic Alzheimer's disease were released. The committee unanimously agreed with 11:0 votes on the efficacy of the drug and unanimously agreed that its benefits outweigh the risks.
This result paves the way for Donanemab to obtain official FDA approval and brings new hope to the field of AD treatment. The drug will now wait for FDA approval.
Donanemab is an A β monoclonal antibody developed by Eli Lilly that can bind to the beta amyloid subtype N3pG, thereby promoting the clearance of amyloid plaques in the patient's brain.
Lilly submitted Donanemab's listing application based on data from Phase II research in October 2021, but was rejected by the FDA in January 2023. After successfully completing the third phase of the study after a 4-month interval, Lilly once again submitted its marketing application for this drug to the FDA.
According to Donanemab's research data, it has significant therapeutic effects in reducing cognitive decline. In the overall population (n=1736), compared with the placebo group, the rate of decline in AD comprehensive assessment scale (iADRS) scores and clinical dementia assessment scale (CDR-SB) scores of patients in the Donanemab group was slowed down by 22% and 29%, respectively.
AD is a progressive and irreversible neurodegenerative disease, with a slow course and insidious onset, often occurring in the elderly population over 60 years old.
The pathogenesis of AD is complex, mainly including the amyloid protein cascade hypothesis, Tau protein phosphorylation hypothesis, and cholinergic hypothesis. Among them, the amyloid protein cascade hypothesis suggests that the deposition of beta amyloid protein (A β) in the brain is the central link of AD pathological changes, which can trigger a series of pathological processes, further promote A β deposition, and form a cascade amplification reaction.
At present, the US FDA has approved two types of A β drugs, namely Adalimumab from Bojian and Lecanemab from Weicai, with approval dates in 2021 and 2023, respectively. However, Adalimumab has been discontinued due to insufficient evidence to suggest that it can benefit patients. However, lencamab has shown significant efficacy in the treatment of Alzheimer's disease, becoming the first AD drug fully approved by the US FDA in nearly 20 years, and confirming the effectiveness of the A β hypothesis, while also opening the door to a new world of treatment for AD. It is worth mentioning that lencamab has been approved for marketing in China in 2024.
At present, there is a huge unmet demand for treatment in the field of Alzheimer's disease, and the A β drug market is booming. Many pharmaceutical companies are laying out their plans, and there are also Chinese pharmaceutical companies developing similar drugs. For example, according to the 2023 annual report of Hengrui Pharmaceutical (600276. SH), the company's innovative drug for Alzheimer's disease, the anti A β monoclonal antibody SHR-1707, is in phase II clinical research.
However, the common side effects of A β drugs are symptoms such as cerebral edema (ARIA-E) and cerebral hemorrhage (ARIA-H) in patients, which affect the treatment prognosis. How to reduce the occurrence of side effects and explore related risk factors is still the focus of exploration for these types of drugs.