New drug listing adventures: Who is the FDA's compromise for?

New drug listing adventures: Who is the FDA's compromise for?

New drug listing adventures: Who is the FDA's compromise for? New drug listing adventures: Who is the FDA's compromise for?

"This is not the first time that the FDA has voted against the expert committee, but as far as I can see, this is the first time that no expert supports a new drug, but the FDA has approved it
.

" Scott Emerson, professor emeritus of the University of Washington, described the magical encounter of a new type of drug in this way

Recently, the US Food and Drug Administration (FDA) announced that it has accelerated the approval of the new drug Aducanumab (trade name Aduhelm) developed by Biogen for the treatment of Alzheimer's disease, but this decision caused an uproar
.

"The FDA's approval of this drug is good news.
It looks more like a'compromise' between science and politics
.

" The expert said in an interview with the "China Science News"

New drugs are born in controversy

New drugs are born in controversy

For a long time, Alzheimer's disease has been regarded as a "terminal disease" that cannibalize the human mind
.

The scientific and medical circles have repeatedly challenged this disease, but most of them have failed

In this context, the debut of Aducanumab, a new drug for Alzheimer's disease, has attracted much attention
.

In September 2016, "Nature" magazine reported the results of the phase I clinical trial of this drug in the form of a cover article, confirming that this drug can effectively remove beta amyloid (Aβ) deposits

Aβ is undoubtedly the "focus star" in the history of Alzheimer's disease research
.

Studies have shown that in almost all brain cells of Alzheimer's disease patients, there will be varying degrees of amyloid deposits, which can directly poison cells and disrupt neurotransmission, and play a very important role in the progression of the disease

"The Alzheimer's disease drugs currently on the market can only improve patients' memory loss and neuronal damage to a limited extent, but cannot directly intervene in the disease process
.

" Kuang Weihong, deputy director and chief physician of the Mental Health Center of West China Hospital The newspaper said, "But people have not been satisfied with'symptomatic treatment', but hope to achieve'cause treatment', that is, directly starting from the pathogenic mechanism of Alzheimer's disease, and fundamentally curbing the development of the disease

Therefore, people are looking forward to Aducanumab becoming "the first treatment for Alzheimer's disease that attacks the disease process and not just relieves symptoms"
.

For this reason, the FDA allowed Bojian to skip the Phase II clinical trial directly and opened two Phase III clinical trials

The results are not optimistic.
The data of the two trials are contradictory.
One trial reported that the cognitive level of patients in the high-dose group improved, and the other trial showed that the cognitive level of patients in the high-dose group was not reduced at all.
Some scores in the high-dose group were instead Worse
.

In March 2019, these two phase III clinical trials were terminated early

At an expert group meeting held in November 2020, 10 of the 11 advisory experts believed that "there is insufficient evidence to support Aducanumab's ability to alleviate cognitive decline", and one person voted "unsure"
.

However, before almost Qing Yishui’s negative vote, the FDA still withstood the pressure and adopted an accelerated approval method for Aducanumab, which caused huge controversy and concerns
.

Why did the FDA "compromise"?

Why did the FDA "compromise"?

The FDA stated in a statement that the accelerated approval of Aducanumab is based on its impact on the "surrogate endpoint", that is, it consistently reduces the level of amyloid in the patient's brain and is "more likely to predict" the clinical benefit to the patient
.

To put it simply, the drug was approved not because it showed a clear therapeutic effect, but because it reduced Aβ deposition, which is considered an important pathological feature of Alzheimer’s disease, so it was considered "possible" The patient is good
.

Regarding this logic, Xiao Shifu, director of the Alzheimer’s Disease Diagnosis and Treatment Center of Shanghai Jiaotong University, has reservations: “No matter what principle a drug adopts, the ultimate criterion should be to benefit the patient
.
For Alzheimer’s disease, it is The patient’s cognitive level, life function, abnormal mental behavior and quality of life have been improved
.
"

"This result now looks more like a compromise between science and politics
.
" Kuang Weihong said bluntly, "Even the FDA, which should be a neutral certification body, seems to be under pressure from the public and society
.
"

To understand this pressure, we have to start with the plight of Alzheimer's disease drug development
.
Alzheimer's disease is called the "Bermuda" of medical research
.
In recent decades, people have carried out a series of drug research and development in response to the two major pathological hypotheses of this disease-the Aβ hypothesis and the Tau protein hypothesis, but they all failed
.

"If we continue to fail without seeing hope, pharmaceutical companies and even scientists may really give up their efforts in this direction, it will be a huge loss for mankind
.
" Kuang Weihong said, "The FDA's green light for new drugs this time also shows One attitude: The research and development of new drugs for Alzheimer's disease based on Aβ and other mechanisms cannot be stopped or given up, at least for now
.
"

Zhang Zhenxin, a professor at Peking Union Medical College Hospital, also believes that despite the unsatisfactory results, the approval of the drug is "good news", bringing new hope to patients and encouraging scientists, medical scientists, and companies to continue to invest in research
.
"The drug is aimed at an important pathological change.
As long as the drug is safe and harmless, it may be an opportunity for everyone
.
"

As Dr.
Maria C.
Carrillo, CEO of the Alzheimer's Association, said-"History tells us that the approval of the first new type of drug will inspire the entire field, stimulate investment in innovative therapies and encourage greater innovation
.
" Some people believe that the FDA's special preferential treatment of Aducanumab can be described as well-intentioned
.

But other people's concerns are equally unavoidable
.
Joseph Ross, an FDA regulatory policy expert at Yale University School of Medicine, emphasized that this means that health insurance providers and patients will pay for a treatment that has not been reliably proven
.

Where will the dawn be in the future?

Where will the dawn be in the future?

"The script is very good, but it's a pity that I can't sing
.
" Kuang Weihong expressed his regret for this new drug many times: "It realizes the classic mechanism that people dream of: blocking or eliminating Aβ deposition, but it does not improve the symptoms of patients.
Good
.
"

In fact, the clinical efficacy of Aducanumab has also caused many people to reflect on: What is the significance of the Aβ hypothesis for the development of Alzheimer's disease drugs?

Zhang Zhenxin’s team has conducted research for many years and found that the relationship between Aβ deposition and Alzheimer’s disease is more complicated than people think: some people have the same cognitive scale scores as normal people, but significant Aβ protein deposition has appeared in the brain.
, Even neurons and hippocampus have been damaged, showing signs of brain atrophy
.

In Zhang Zhenxin's view, this does not mean that the idea of ​​finding a treatment method through the Aβ hypothesis is wrong.
On the contrary, it just shows that the Aβ hypothesis still has huge room for exploration
.
The problem in the past was that on the one hand, we did not fully understand the disease; on the other hand, the evaluation method was not perfect.
In the past, the cognitive function scale was usually used to evaluate whether the drug was effective
.
However, the scale is mostly aimed at moderate to severe patients, and cannot accurately reflect the status of mild patients.
The problem is simple and needs to be redesigned
.

She also said that in order to truly conquer Alzheimer's disease, it may not be enough to focus on a single target such as Aβ.
We should expand our thinking and take more potential influencing factors into consideration
.

"It's like a cocktail therapy for AIDS, using multiple anti-HIV drugs at the same time, the effect is better.
This concept is a direction for future efforts
.
" Kuang Weihong pointed out that the future of Alzheimer's disease may be broken by Multiple mechanisms to intervene together, such as combining drugs that have a clearing effect on abnormal protein deposits such as Aβ and tau protein, drugs that have a protective effect on mitochondrial function damage, and various non-drug therapies to develop a series of comprehensive treatments Scheme
.

In addition, Zhang Zhenxin emphasized that in view of the limitations of human response to Alzheimer's disease, the front should be moved forward.
Early diagnosis and early intervention are critical, and "full disease management" throughout the life cycle should be done
.