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SEVIGNY ET AL.
, NATURE, 537, 50 (2016) On June 7, the U.
S.
Food and Drug Administration (FDA) announced the approval of the new anti-Alzheimer’s disease drug aducanumab ( The trade name is Aduhelm) through the accelerated approval channel.
This is the first time the FDA has approved the listing of a new anti-Alzheimer's disease drug after a lapse of 18 years
.
However, many scientists have questioned the effectiveness of the drug
.
At the FDA's advisory panel meeting before the approval, the evaluation members almost unanimously gave their denials
.
Can this new drug bring light to patients with Alzheimer's disease? CompilationLi Shiyuan Yang Xinzhou Medicine of Hope In 2016, a cover article in the top international academic journal "Nature" showed two colorful "brains"
.
This is the brain imaging of patients with Alzheimer's disease before and 54 weeks after treatment with a drug, which was aducanumab, which was still in phase I clinical trials at that time
.
The results of the test showed that after receiving aducanumab injection once a month for 1 year, patients with prodromal Alzheimer's disease or mildly ill patients had decreased β-amyloid deposits in the brain and cognitive function The recession has also been delayed
.
Alzheimer's disease is an irreversible progressive brain dysfunction, mostly in elderly people around 65 years old
.
The patient's memory and thinking ability will gradually decline until they cannot complete simple tasks in daily life, which is commonly referred to as "Alzheimer's disease
.
"
It is estimated that more than 6 million people suffer from this disease in the United States alone
.
Previously, the FDA has approved several drugs for the treatment of various degrees of Alzheimer's disease
.
Although the mechanisms of these drugs are different, their effects are limited to reducing or delaying symptoms, maintaining the patient's ability to complete daily tasks, etc.
, and cannot cure diseases
.
The brown part is β-amyloid
.
(Image source: NATIONAL INSTITUTE ON AGING/NIH) At present, it is generally believed that the deposition of β-amyloid in the brain is the main cause of Alzheimer's disease
.
This protein aggregates around neurons in the patient's brain to form plaques, blocking communication between neurons, causing synaptic dysfunction, and ultimately killing neurons
.
This mechanism is called the "amyloid hypothesis" (amyloid hypothesis)
.
Many basic studies have shown that therapies for β-amyloid may improve the symptoms of patients with Alzheimer's disease, but there is no clinical treatment that can achieve this
.
Before aducanumab, there were already a variety of drugs targeting β-amyloid, including products from pharmaceutical giants such as Merck & Co.
and Roche
.
And aducanumab's own experience has not been smooth sailing
.
Biogen and Eisai have recruited more than 3,000 patients in 20 countries and regions around the world, and carried out two 18-month phase III clinical trials, code-named 301 and 302, respectively
.
In March 2019, the two companies announced the termination of these two trials because the results of interim data analysis showed that aducanumab had no effect
.
But in October of the same year, Biogen suddenly announced a shocking decision-to apply for aducanumab marketing authorization from the FDA
.
It turned out that after including more subjects' data compared to the interim analysis, the analysis results were reversed: in the 302 trial, the clinical dementia rating scale (CDR) score of the high-dose group compared with the placebo group A reduction of 22% indicates that the patient’s cognitive decline has been significantly delayed and the primary endpoint has been reached
.
However, in the 301 trial, the cognitive decline of subjects in the high-dose group was even slightly more severe than that of the placebo group
.
The FDA also decided to speed up the approval based on the results of the 302 trial
.
Willingly go its own way? However, the FDA's approach has aroused the concern of many scientists, who believe that this move is an extremely dangerous impact on drug standards
.
Joseph Ross of Yale School of Medicine has been studying the FDA's management policies for a long time.
He believes that "FDA's approval of this new drug may have extremely serious consequences for it and the entire medical system
.
" The FDA has never had such a precedent for a drug.
In the absence of evidence of clinical improvement, the standard approval procedure is changed, which directly becomes "accelerated approval
.
"
Aducanumab is considered a precedent, and the FDA’s criterion for making a decision is that the drug may reduce β-amyloid deposits
.
In fact, the FDA's actions did exceed many people's expectations
.
In December last year, an independent advisory team reviewed and evaluated the aducanumab data.
.
At the meeting at that time, the heads of the FDA and Biogen took the 302 trial as an example and pointed out that there is strong evidence that aducanumab can be effective
.
Samantha Budd Haeberlein, chief scientist in the direction of neurodegenerative development at Biogen, said that they did not ignore the negative results of the 301 trial.
“After working with the FDA, we found the reason for the failure of the 301 trial
.
” They proposed that the 302 trial was compared to the 301 trial.
The effect can be seen because the subjects who participated in this batch of studies received sustained high doses of the drug
.
In addition, patients in the 301 trial had more rapid cognitive decline (18 in the 301 trial and 13 in the 302 trial)
.
If these patients in the 301 trial are set to be the same as those in the 302 trial, then the high-dose aducanumab can also be seen in this group to improve the symptoms of cognitive decline
.
The FDA Office of Neuroscience also agrees with this statement and believes that the negative results of the 301 trial cannot deny the success of the 302 trial
.
Image source: Pixabay, but members of the advisory panel did not accept these views.
According to an analysis report provided by the FDA data reviewer, "there is no substantial evidence that aducanumab has a therapeutic effect
.
" The advisory panel said that the FDA should not pay attention to the 301 trial.
It is also difficult to understand
.
Scott Emerson, a statistician at the University of Washington, said that the two studies were originally to be evaluated together.
“It is absolutely impossible to ignore the 301 trial
.
” Neuroscientist Michael Gold added: “For the FDA, the 302 trial is recognized and the 301 trial is denied.
It is a tactical strategy
.
"Even if the FDA and Biogen's selective reference practices are ignored, the advisory panel is not optimistic about the results of the 302 trial
.
Some members believe that aducanumab itself will cause the side effects of brain swelling and may cause deviations in the experimental results
.
And from the perspective of practical application, The 22% improvement in cognitive decline that aducanumab can provide is almost "minimal
.
"
Regarding the question of "whether trial 302 is used as evidence that aducanumab can effectively treat Alzheimer's disease", during the voting session, 11 members of the advisory panel Among them, 10 gave no and 1 gave it uncertain
.
In
other words, the advisory panel did not recommend that the FDA approve the drug for marketing
.
But this time, the FDA can be said to have done its own way
.
You
know that in the past, About 89% of the applications’ opinions, the FDA and the advisory group’s recommendations are consistent
.
For the
remaining 10% of the cases where the opinions are not uniform, most of the advisory groups have given recommendations for approval, and the FDA has adopted more stringent recommendations.
The request was rejected
.
The situation like aducanumab can be said to be extremely rare
.
Whether aducanumab is the magic drug for Alzheimer's disease, many researchers have their own criteria for judgment
.
In the past, everyone has always dealt with it .
β-amyloid as a standard treatment for Alzheimer's disease, FDA approval for the study seems to be the direction of a man shot in the arm
.
the FDA currently requires Biogen after approval to conduct clinical trials to demonstrate the beneficial effects of the drug
.
If The effect is not good, FDA still has the right to withdraw approval
.
Reference link: https:// https:// https :// https:// https:// /news/2021/06/alzheimer-s-drug-approved-despite-doubts-about-effectiveness https://investors.
biogen.
com/static-files/74641e1b-cd23-495e-8f29-f4ecac0a1126 https://www .
sciencemag.
org/news/2019/03/another-major-drug-candidate-targeting-brain-plaques-alzheimer-s-disease-has-failed "Global Science" June new issue is now available Stamp the picture or read the original text immediately To purchase, click [Looking] to receive our content updates in time
, NATURE, 537, 50 (2016) On June 7, the U.
S.
Food and Drug Administration (FDA) announced the approval of the new anti-Alzheimer’s disease drug aducanumab ( The trade name is Aduhelm) through the accelerated approval channel.
This is the first time the FDA has approved the listing of a new anti-Alzheimer's disease drug after a lapse of 18 years
.
However, many scientists have questioned the effectiveness of the drug
.
At the FDA's advisory panel meeting before the approval, the evaluation members almost unanimously gave their denials
.
Can this new drug bring light to patients with Alzheimer's disease? CompilationLi Shiyuan Yang Xinzhou Medicine of Hope In 2016, a cover article in the top international academic journal "Nature" showed two colorful "brains"
.
This is the brain imaging of patients with Alzheimer's disease before and 54 weeks after treatment with a drug, which was aducanumab, which was still in phase I clinical trials at that time
.
The results of the test showed that after receiving aducanumab injection once a month for 1 year, patients with prodromal Alzheimer's disease or mildly ill patients had decreased β-amyloid deposits in the brain and cognitive function The recession has also been delayed
.
Alzheimer's disease is an irreversible progressive brain dysfunction, mostly in elderly people around 65 years old
.
The patient's memory and thinking ability will gradually decline until they cannot complete simple tasks in daily life, which is commonly referred to as "Alzheimer's disease
.
"
It is estimated that more than 6 million people suffer from this disease in the United States alone
.
Previously, the FDA has approved several drugs for the treatment of various degrees of Alzheimer's disease
.
Although the mechanisms of these drugs are different, their effects are limited to reducing or delaying symptoms, maintaining the patient's ability to complete daily tasks, etc.
, and cannot cure diseases
.
The brown part is β-amyloid
.
(Image source: NATIONAL INSTITUTE ON AGING/NIH) At present, it is generally believed that the deposition of β-amyloid in the brain is the main cause of Alzheimer's disease
.
This protein aggregates around neurons in the patient's brain to form plaques, blocking communication between neurons, causing synaptic dysfunction, and ultimately killing neurons
.
This mechanism is called the "amyloid hypothesis" (amyloid hypothesis)
.
Many basic studies have shown that therapies for β-amyloid may improve the symptoms of patients with Alzheimer's disease, but there is no clinical treatment that can achieve this
.
Before aducanumab, there were already a variety of drugs targeting β-amyloid, including products from pharmaceutical giants such as Merck & Co.
and Roche
.
And aducanumab's own experience has not been smooth sailing
.
Biogen and Eisai have recruited more than 3,000 patients in 20 countries and regions around the world, and carried out two 18-month phase III clinical trials, code-named 301 and 302, respectively
.
In March 2019, the two companies announced the termination of these two trials because the results of interim data analysis showed that aducanumab had no effect
.
But in October of the same year, Biogen suddenly announced a shocking decision-to apply for aducanumab marketing authorization from the FDA
.
It turned out that after including more subjects' data compared to the interim analysis, the analysis results were reversed: in the 302 trial, the clinical dementia rating scale (CDR) score of the high-dose group compared with the placebo group A reduction of 22% indicates that the patient’s cognitive decline has been significantly delayed and the primary endpoint has been reached
.
However, in the 301 trial, the cognitive decline of subjects in the high-dose group was even slightly more severe than that of the placebo group
.
The FDA also decided to speed up the approval based on the results of the 302 trial
.
Willingly go its own way? However, the FDA's approach has aroused the concern of many scientists, who believe that this move is an extremely dangerous impact on drug standards
.
Joseph Ross of Yale School of Medicine has been studying the FDA's management policies for a long time.
He believes that "FDA's approval of this new drug may have extremely serious consequences for it and the entire medical system
.
" The FDA has never had such a precedent for a drug.
In the absence of evidence of clinical improvement, the standard approval procedure is changed, which directly becomes "accelerated approval
.
"
Aducanumab is considered a precedent, and the FDA’s criterion for making a decision is that the drug may reduce β-amyloid deposits
.
In fact, the FDA's actions did exceed many people's expectations
.
In December last year, an independent advisory team reviewed and evaluated the aducanumab data.
.
At the meeting at that time, the heads of the FDA and Biogen took the 302 trial as an example and pointed out that there is strong evidence that aducanumab can be effective
.
Samantha Budd Haeberlein, chief scientist in the direction of neurodegenerative development at Biogen, said that they did not ignore the negative results of the 301 trial.
“After working with the FDA, we found the reason for the failure of the 301 trial
.
” They proposed that the 302 trial was compared to the 301 trial.
The effect can be seen because the subjects who participated in this batch of studies received sustained high doses of the drug
.
In addition, patients in the 301 trial had more rapid cognitive decline (18 in the 301 trial and 13 in the 302 trial)
.
If these patients in the 301 trial are set to be the same as those in the 302 trial, then the high-dose aducanumab can also be seen in this group to improve the symptoms of cognitive decline
.
The FDA Office of Neuroscience also agrees with this statement and believes that the negative results of the 301 trial cannot deny the success of the 302 trial
.
Image source: Pixabay, but members of the advisory panel did not accept these views.
According to an analysis report provided by the FDA data reviewer, "there is no substantial evidence that aducanumab has a therapeutic effect
.
" The advisory panel said that the FDA should not pay attention to the 301 trial.
It is also difficult to understand
.
Scott Emerson, a statistician at the University of Washington, said that the two studies were originally to be evaluated together.
“It is absolutely impossible to ignore the 301 trial
.
” Neuroscientist Michael Gold added: “For the FDA, the 302 trial is recognized and the 301 trial is denied.
It is a tactical strategy
.
"Even if the FDA and Biogen's selective reference practices are ignored, the advisory panel is not optimistic about the results of the 302 trial
.
Some members believe that aducanumab itself will cause the side effects of brain swelling and may cause deviations in the experimental results
.
And from the perspective of practical application, The 22% improvement in cognitive decline that aducanumab can provide is almost "minimal
.
"
Regarding the question of "whether trial 302 is used as evidence that aducanumab can effectively treat Alzheimer's disease", during the voting session, 11 members of the advisory panel Among them, 10 gave no and 1 gave it uncertain
.
In
other words, the advisory panel did not recommend that the FDA approve the drug for marketing
.
But this time, the FDA can be said to have done its own way
.
You
know that in the past, About 89% of the applications’ opinions, the FDA and the advisory group’s recommendations are consistent
.
For the
remaining 10% of the cases where the opinions are not uniform, most of the advisory groups have given recommendations for approval, and the FDA has adopted more stringent recommendations.
The request was rejected
.
The situation like aducanumab can be said to be extremely rare
.
Whether aducanumab is the magic drug for Alzheimer's disease, many researchers have their own criteria for judgment
.
In the past, everyone has always dealt with it .
β-amyloid as a standard treatment for Alzheimer's disease, FDA approval for the study seems to be the direction of a man shot in the arm
.
the FDA currently requires Biogen after approval to conduct clinical trials to demonstrate the beneficial effects of the drug
.
If The effect is not good, FDA still has the right to withdraw approval
.
Reference link: https:// https:// https :// https:// https:// /news/2021/06/alzheimer-s-drug-approved-despite-doubts-about-effectiveness https://investors.
biogen.
com/static-files/74641e1b-cd23-495e-8f29-f4ecac0a1126 https://www .
sciencemag.
org/news/2019/03/another-major-drug-candidate-targeting-brain-plaques-alzheimer-s-disease-has-failed "Global Science" June new issue is now available Stamp the picture or read the original text immediately To purchase, click [Looking] to receive our content updates in time
