Pfizer and others go forward and continue AD research and development stagnant, can Bojian Aducanumab stand out?

Text | pharm_rookie

June 7th, US time, is the deadline for the FDA to decide whether to approve Biogen's Alzheimer's drug Aducanumab.
As one of the most difficult decisions in FDA history, I believe that no matter what decision the FDA makes, it will definitely do so.
Caused an uproar
.
According to the ranking of the most anticipated new drugs in 2021 made by the well-known foreign media Fierce Pharma, Aducanumab is at the top of the list.

As one of the most difficult medical challenges of this era, the research and development of Alzheimer's drugs has been on the most difficult road, and the development of Aducanumab is also full of hardships and doubts.
Aducanumab, ushering in the moment of trial, will undoubtedly take people’s attention.
It also focuses on the current global Alzheimer's disease drug research and development situation
.

01 Only a few drugs have been approved for decades, and the treatment of Alzheimer's disease has been stagnant

Alzheimer's disease (AD) refers to degenerative diseases of the central nervous system that occur in old age and pre-senility and are characterized by progressive cognitive dysfunction and behavioral impairment
.
The clinical performance of memory impairment, aphasia, apraxia, agnosia, impaired visuospatial ability, abstract thinking, changes in personality and behavior and so on

Correspondingly, the FDA has approved several cholinesterase (AChE) inhibitor drugs for alleviating patients’ related symptoms since 1993, although scientific research so far has not fully proven that cholinesterase inhibitors are effective for treatment.
The exact mechanism of Alzheimer's disease
.
In 2004, the FDA approved the listing of an excitatory amino acid receptor (NMDA) inhibitor Namenda (Memantine) to relieve the corresponding symptoms of patients with moderate to severe Alzheimer's disease

Picture from NIH official website

In November 2019, the drug Mannote Sodium Capsules (trade name: Phase 1) developed by Green Valley Pharmaceuticals was approved for marketing in China.
However, like Aducanumab, the drug is always full of controversy from development to marketing.
Professor Yue Raoyi's bombardment of the ninth phase 1 incident also pushed the doubts from all walks of life to a new climax
.
Amidst doubts, Green Valley Pharmaceuticals also announced a plan to invest 3 billion US dollars in early 2020, saying that it will support the ninth phase one post-marketing real-world research, the international multi-center phase Ⅲ clinical research "green memory", and expand the adaptation.

02 Mechanism hypotheses are emerging one after another, and various pharmaceutical companies have made efforts

Since the pathogenesis of Alzheimer's disease has not been fully studied yet, the development of most new drugs has also announced "breaking down the sand"
.
Nevertheless, the medical community has never stopped research on the pathogenesis of the disease.

According to incomplete statistics, the failure rate of new drugs for Alzheimer's disease is as high as 99.
6%.
Since the beginning of the 21st century, more than 320 clinical trials have failed.
This has become the "Waterloo" of countless pharmaceutical companies
.
Even though many pharmaceutical companies went to the field of Alzheimer's disease, most of them ended in failure.

In January 2018, Pfizer announced that it would stop the discovery and research of Alzheimer's disease and Parkinson's treatment drugs.
So far, there is no news that Pfizer will continue to deploy in the field of Alzheimer's disease;

In June 2018, Eli Lilly and AstraZeneca jointly announced the termination of the Phase III clinical study of the BACE inhibitor Lanabestat.
Earlier, a Phase III trial of Lilly Solanezumab for the treatment of AD also announced failure.
The trial results showed that Solanezumab could not significantly delay AD patients Decline in cognitive abilities;

In 2019, Roche announced the failure of two phase III trials of Crenezumab in the treatment of AD because Crenezumab may not reach the primary endpoint of improving the clinical dementia comprehensive rating scale (CDR-SB score);

In January 2021, Biohaven Pharmaceuticals announced that its EAAT2 inhibitor Troriluzole had once again failed in a phase II/III clinical study for the treatment of mild to moderate Alzheimer's disease
.

Despite failures time and time again, in the face of huge gaps in the drug market and huge profit margins in the future, there are still one after another "adventurous players" joining the track one after another
.

Due to the miserable failure of many drugs on the amyloid cascade hypothesis, the industry has gradually turned its attention to Tau protein and more mechanisms of action
.
In the article "Alzheimer's disease drug development pipeline: 2020" published in June last year, a detailed inventory of the mechanism of action of Alzheimer's drugs in recent years was also made

Statistics show that there are at least 50 million Alzheimer's disease patients in the world, and it is expected to reach 150 million by 2050
.
Among them, China has the largest number of patients with Alzheimer's disease, about 10 million

The picture is compiled from the drug clinical trial registration and information disclosure platform

03 After Alzheimer's disease drugs are marketed, there are still many obstacles

According to reports, after the launch of Phase Nine, a single box of drugs is priced at 895 yuan, the monthly cost of medication is 3580 yuan (calculated on a 28-day basis), and the annual medication cost is about 40,000 yuan.
It has not been included in the medical insurance at present.
Within range
.
In China, where the population is seriously aging, this cost is not a small burden for many patients
.

Similarly, Aducanumab’s pricing has also encountered certain controversy and resistance.
Although the specific price has not yet been announced, the American Institute of Clinical and Economic Review (ICER) has considered that the evidence for the benefits of Aducanumab to patients is “insufficient”.
The price of a drug can only be considered cost-effective at about US$2500-8300 per year.
The price is far below the US$50,000 mark estimated by industry observers.
For Biogen, this price is clearly unacceptable
.

In academia, Aducanumab and Phase 9 have also been greatly questioned.
During the drug review period, the FDA's internal opposition to this drug was incessant.
Among them, the Peripheral and Central Nervous System Drug Advisory Committee and its members have repeatedly spoken Aducanumab was strongly criticized in conferences and documents
.
It is understood that Goodman, an expert in Alzheimer’s disease research, said in an interview with the media: “The Phase III clinical data currently displayed by Aducanumab lacks a certain degree of persuasiveness.
Unless the patient or their family members ask me to use Aducanumab for treatment, that’s it.
I will not take the initiative to choose drugs if it is approved for listing
.
"

For patients, in addition to the potentially high cost of the drug itself, the PET scan and cerebrospinal fluid amyloid test used in the treatment of Aducanumab are currently not covered by U.
S.
medical insurance.
In addition, patients need to be followed up regularly during Aducanumab treatment.
As well as monitoring, it is also a big challenge to the current medical system
.

As one of many Alzheimer's disease treatment drugs in the development process, Aducanumab is undoubtedly lucky.
It has reached the final stage, and it also brings a profound effect to the development of Alzheimer's disease drugs in the future.
Thinking
.
How to deal with the industry's doubts, high drug prices, and adapt to the existing medical system are all issues that need to be resolved urgently after the launch of Alzheimer's drugs
.
It is not easy for Alzheimer's drugs to be marketed.
Don't let all the efforts made in the previous decades be wasted because of various problems after the market
.