On June 7th, the US FDA announced approval for Bojian/Weicai Company Aβ (β Amyloid protein) antibody Aduhelm (aducanumab) Application for Biological Product License (BLA) for the treatment of early Alzheimer's disease (AD) patients. Aducanumab is a new drug approved by the FDA for the treatment of Alzheimer's disease since 2003
Alzheimer's disease (AD) is the most common type of dementia in the elderly, characterized by progressive degeneration of the nervous system and an important cause of disability in the elderly. This disease can cause damage to thinking, memory, and independence, leading to premature death of patients. AD is an increasingly serious global health crisis. According to data released by the World Health Organization (WHO), there are tens of millions of AD patients worldwide, and this number will continue to grow in the coming years
The currently recognized pathogenesis of Alzheimer's disease is believed to be beta; Imbalance in the generation and clearance of amyloidβ (Aβ) is a initiating factor in neuronal degeneration and dementia, with abnormal levels of&beta- Amyloid plaques formed between brain neurons are neurotoxic, leading to neuronal degeneration
Aducanumab is a high affinity, targeted - Aβ Whole human IgG1 monoclonal antibody with conformational epitopes. It can selectively bind to amyloid protein deposition in the brain of AD patients, and then clear the deposited proteins in the brain by activating the immune system. In November 2007, Bojian obtained a research and development license for aducanumab from Neurimmune. Since October 2017, Bojian and Weicai have been collaborating globally in the development and commercialization of Aducanumab
The path of Aducanumab's listing can be described as a bumpy one. As early as March 2019, the ENGAGE and EMERGE studies were terminated prematurely due to an independent committee assessment that it was unlikely to improve cognitive function in AD patients. Stimulated by this news, Baijian's stock price plummeted by 27% in pre market trading, and its market value instantly shrank by as much as $15 billion. At the same time, Biogen also prematurely terminated the Phase II EVOLVE safety study and the Phase Ib PRIME extension trial of Aducanumab
However, after analyzing the larger data set, Biogen medical data Statistician found that in the EMERGE study, the cognitive ability score (CDR-SB) of AD patients receiving high-dose aducanumab treatment at the 78th week was significantly reduced by 23% compared with the control group, reaching the main endpoint. In addition, in several other secondary endpoint indicators, the high-dose aducanumab treatment group also showed a continuous decreasing effect compared to placebo. The imaging data also showed that the burden of amyloid plaques in the aducanumab treatment group was significantly reduced compared to the placebo group at weeks 26 and 78. So, Biogen communicated with the FDA after receiving the analysis conclusion and announced in October 2019 that it would submit a decision to the BLA
EMERGE research data released at the 2021 AD/PD virtual conference
Key clinical data from three studies
On July 8, 2020, Biogen completed the submission of aducanumab listing application materials. On August 7, 2020, it was officially accepted by the FDA and qualified for priority review. The PDUFA date was set for March 7, 2021
On November 6, 2020, the FDA convened an advisory committee to discuss this BLA application. The FDA Advisory Committee on Peripheral and Central Nervous System Drugs addresses the issue of; Not to mention ENGAGE research, does EMERGE research alone provide strong evidence to support the efficacy of aducanumab in treating Alzheimer's disease& Rdquo; I voted against the issue with 8:1 (2 uncertain votes). And for&quo; Does PRIME research support the effectiveness of drugs; I also voted against it with a vote of 7:0 (4 uncertain). Overall, the committee is opposed to the listing of Aducanumab
Voting status of the FDA advisory committee on four issues
On January 29th of this year, Biogen and Eisai announced that the FDA has postponed the PDUFA date for aducanumab by three months. As part of the ongoing review, Biogen submitted a response to the FDA's request for information, including additional analysis and clinical data. The FDA believes that this is a significant modification to the BLA and requires additional review time
In early April of this year, three members of the FDA's Peripheral and Central Nervous System Drug Advisory Committee&# 8217& Flash; Caleb Alexander, Scott Emerson, and Aaron Kesselheim expressed their opposition to the drug in an article by JAMA. They once again elaborated on the reasons why the FDA should reject the listing of aducanumab, focusing on the conflicting results between Biogen's two key experiments and the potential safety hazards that emerged in the study. And it was stated that regulatory agencies may compromise objective judgment due to their close cooperation with the company
Alzheimer's disease is a serious disaster area for Drug development, and several therapies under research are in later clinical trials“ Breaking the halberd and sinking the sand;. Aducanumab as a target A&beta approved for listing; The therapy will also give confidence to drug research and development enterprises in this field. According to the NextPharma database of the Medical Cube, there are currently more than 40 companies worldwide developing Aβ Targeted drugs. According to a report released by pharmaceutical market research firm Evaluate Vantage, aducanumab's global sales in 2026 will reach $4.8 billion
