On June 7, the US FDA announced the approval of Biogen/Eisai’s Aβ (amyloid β) antibody Aduhelm (aducanumab) for the treatment of early-stage Alzheimer’s disease (AD) patients with a biological product license (BLA) application. aducanumab, the first new drug approved by the FDA for the treatment of AD since 2003.
Alzheimer’s disease is the most common type of senile dementia. It is characterized by progressive neurological degeneration and is an important cause of disability in the elderly. The disease can cause impaired thinking, memory, and independence, leading to premature death.
AD is an increasingly serious global health crisis. According to data released by the World Health Organization, there are tens of millions of AD patients worldwide, and this number will increase in the next few years.
At present, the well-recognized pathogenesis of Alzheimer’s disease believes that the production and clear imbalance of amyloid-β is the initiating factor for neuronal degeneration and dementia. The abnormal level of amyloid-β in the plaques formed between brain neurons has nerves. Toxic, causing neuronal degeneration.
Aducanumab is a high-affinity, fully human IgG1 monoclonal antibody targeting-Aβ conformational epitope. It can selectively bind to the amyloid deposits in the brains of AD patients and then clear the deposits in the brains by activating the immune system. In November 2007, Bojian obtained the R&D license of aducanumab from Neurimmune. Since October 2017, Bojian and Eisai have jointly developed and commercialized aducanumab globally.
Aducanumab’s road to market can be described as ups and downs. As early as March 2019, the ENGAGE and EMERGE studies were terminated early due to independent committee evaluations that it is unlikely to improve the cognitive function of AD patients.
Stimulated by this news, Biogen’s stock price plummeted by 27% during the pre-market trading stage, and its market value instantly shrank by as much as 15 billion US dollars. At the same time, Biogen also terminated aducanumab’s Phase II EVOLVE safety study and the extended experiment of the Phase Ib PRIME study ahead of schedule.
However, after analyzing a larger data set, Biogen medical data statisticians found that in the EMERGE study, AD patients treated with high-dose aducanumab had a significant reduction in cognitive performance scores at week 78 compared to the control group by 23% , reached the primary endpoint. In addition, on several other secondary endpoints, the high-dose aducanumab treatment group also showed a continuous decrease effect compared with placebo.
The imaging data also showed that the amyloid plaque burden level in the aducanumab treatment group at 26 and 78 weeks was significantly reduced compared with the placebo group. Therefore, Biogen communicated with the FDA after obtaining the latest analysis conclusion, and announced in October 2019 that it would submit the BLA decision.
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 obtained priority review qualification. The PDUFA date is set to March 7, 2021.
On November 6, 2020, the FDA convened an advisory committee to discuss this BLA application. The FDA’s Peripheral and Central Nervous System Drug Advisory Committee voted 8:1 (2 votes) on the question of “not to mention the ENGAGE study, from the EMERGE study alone, is there strong evidence to support the superiority of aducanumab in the treatment of AD?” Not sure) against. And for “whether the PRIME study supports the effectiveness of the drug” was also voted against with 7:0 (4 votes in doubt). In general, the committee is opposed to the listing of aducanumab.
On January 29 this year, Biogen and Eisai announced that the FDA had postponed the PDUFA date of aducanumab by 3 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 considers this to be a major modification to the BLA and requires additional review time.
In early April of this year, three members of the US FDA’s Peripheral and Central Nervous System Drug Advisory Committee-Caleb Alexander, Scott Emerson, and Aaron Kesselheim published their opposition to the drug in an article in JAMA. They once again elaborated on the reasons why the FDA should reject aducanumab from the market, focusing on the conflicting results between two key Biogen experiments and the potential safety hazards in the study. He also stated that the regulator may undermine objective judgment due to the close cooperation with the company.
As Alzheimer’s disease is the hardest hit area for drug development, many research therapies have ” costly failures” in later clinical trials. Aducanumab, as the first approved therapy to target Aβ, will also give drugs in this field R&D corporate information. There are currently more than 40 companies in the world developing Aβ targeted drugs. The pharmaceutical market research organization Evaluate Vantage released a report predicting that aducanumab’s global sales will reach 4.8 billion U.S. dollars in 2026.