近20年來美FDA首次批准治療阿茲海默症新藥

美國食品及藥物管理局(FDA)7日通過首款有助於減緩阿茲海默症(Alzheimer's disease)認知退化的藥物。研究證明，美國藥廠百健(Biogen)研發、名稱為Aducanumab的新藥，可以讓阿茲海默症引起的輕度認知障礙及早期失智症(dementia)，雙雙獲得改善。根據估計，每名阿茲海默症患者使用Aducanumab，一年下來估計花費為5萬元。

華盛頓郵報指出，這是第一款證實可以減緩腦部功能退化而獲得食藥局通過的新藥，不只是僅僅能夠舒緩症狀而已。從2003年以來，並沒有任何阿茲海默症獲得食藥局通過，由此可見阿茲海默症藥物研發失敗率極高。

Aducanumab新藥研發過程中，曾引發正反兩派論戰。支持者認為，這款藥品獲得食藥局核可之後，可望引來各界對於阿茲海默症更高關注，進而帶動對於治療阿茲海默症解方的更多研究與投資。

百健藥廠表示，Aducanumab的問世能讓阿茲海默症患者爭取到更多寶貴時間與家人相處，患者的日常生活也可以自理，例如清潔、購物等。

Aducanumab是實驗室研發的蛋白質「單株抗體」(monoclonal antibody)，必須透過靜脈注射，啟動患者體內的反疫反應，清除腦部澱粉蛋白斑塊。百健藥廠強調，這款藥品並不會治好阿茲海默症。

然而，反對派人士則表示，Aducanumab藥品是否確實有效，數據資料薄弱，食藥局為這款新藥放行，反映出主管機關迫於病患及倡議團體壓力之下，降低審查標準。

「阿茲海默症協會」(Alzheimer's Association)指出，美國目前約有620萬名阿茲海默症患者，如果沒有突破療法出現，患者人數到了2050年可望翻倍。

文章來源：www.worldjournal.com/wj/story/121469/5516439

FDA’s Decision to Approve New Treatment for Alzheimer’s Disease

By Dr. Patrizia Cavazzoni, Director, FDA Center for Drug Evaluation and Research

Today FDA approved Aduhelm (aducanumab) to treat patients with Alzheimer’s disease using the Accelerated Approval pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.

This approval is significant in many ways. Aduhelm is the first novel therapy approved for Alzheimer’s disease since 2003. Perhaps more significantly, Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain.  The clinical trials for Aduhelm were the first to show that a reduction in these plaques—a hallmark finding in the brain of patients with Alzheimer’s—is expected to lead to a reduction in the clinical decline of this devastating form of dementia.

We are well-aware of the attention surrounding this approval. We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review. Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.

At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward. We examined the clinical trial findings with a fine-tooth comb, we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, we listened to the perspectives of the patient community, and we reviewed all relevant data. We ultimately decided to use the Accelerated Approval pathway—a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit. In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.

What the Data Show
The late-stage development program for Aduhelm consisted of two phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint.  In all studies in which it was evaluated, however, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion.  It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline.

We know that the Peripheral and Central Nervous System Drugs Advisory Committee, which convened in November 2020 to review the clinical trial data and discuss the evidence supporting the Aduhelm application, did not agree that it was reasonable to consider the clinical benefit of the one successful trial as the primary evidence supporting approval. The option of Accelerated Approval was not discussed by the Advisory Committee. As mentioned above, treatment with Aduhelm was clearly shown in all trials to substantially reduce amyloid beta plaques. This reduction in plaques is reasonably likely to result in clinical benefit. After the Advisory Committee provided its feedback, our review and deliberations continued, and we decided that the evidence presented in the Aduhelm application met the standard for Accelerated Approval. We thank the Advisory Committee for its independent review of the data and valuable advice.

Accelerated Approval
The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need.  Approval is based on a surrogate or intermediate clinical endpoint (in this case reduction of amyloid plaque in the brain).  A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.

Drug companies are required to conduct post-approval studies to verify the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial does not verify the drug’s anticipated clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market. 

The Devastation of Alzheimer’s Disease
With all this said, we are extremely aware of the gradual and cumulative devastation that Alzheimer’s disease causes, as patients lose their memory and cognitive functioning over time. In late-stage disease, people can no longer hold a conversation or respond to their environment. On average, a person with Alzheimer’s disease lives four to eight years after diagnosis, but some patients can live up to 20 years with the disease. 

The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimer’s disease and this number is expected to grow as the population ages. Alzheimer's is the sixth leading cause of death in the United States.

Although the Aduhelm data are complicated with respect to its clinical benefits, FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients.  As a result of FDA’s approval of Aduhelm, patients with Alzheimer’s disease have an important and critical new treatment to help combat this disease.  

FDA will continue to monitor Aduhelm as it reaches the market and ultimately the patient’s bedside. Additionally, FDA is requiring Biogen to conduct a post-approval clinical trial to verify the drug’s clinical benefit. If the drug does not work as intended, we can take steps to remove it from the market. But hopefully, we will see further evidence of benefit in the clinical trial and as greater numbers of people receive Aduhelm. As an agency, we will also continue to work to foster drug development for this catastrophic disease.

文章來源：www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease?fbclid=IwAR2_dfZqAgfSkGGHOcLFtrZvjsTYuDvhB9kymPQr7C3y4pzi9vBLzw_XgRA