Bojian, an American pharmaceutical company： It used to sell 700,000 yuan at a time, but now it’s a layoff stop loss.
In July 2020, the topic of "701,000 needles of rare diseases and drugs" rushed to Baidu hot search. This "high-priced medicine" is SMA
(Spinal muscular atrophy)
A revolutionary product in the field, Nosenac sodium. Behind the public opinion boom, its R&D manufacturer Bo Jian
（Biogen）
, and therefore is widely known in China.
(Spinal muscular atrophy)
A revolutionary product in the field, Nosenac sodium. Behind the public opinion boom, its R&D manufacturer Bo Jian
（Biogen）
, and therefore is widely known in China.
SMA is the abbreviation of spinal muscular atrophy, which is called "the number one killer of genetic diseases in infants". Shortly after birth, children with SMA gradually lose all kinds of motor functions, including breathing and swallowing. If there is no specific medicine, most children will not live beyond 2 years old.
Nocicnatrium is the world’s first precise targeting drug for SMA. More than 1,600 children registered nationwide need lifelong medication, with 1.4 million in the first year and an average annual expenditure of 1.05 million thereafter. The people’s livelihood of rare diseases affects the heart of the Prime Minister, who pushes rare diseases into medical insurance to reduce the burden on the people.
At the national medical insurance negotiation at the end of 2021, Nosenac sodium was successfully included in the national medical insurance catalogue, with a dose of 33,000 yuan per needle.
After a few months, Bojian was once again concerned by the public, but it was full of negative keywords such as "layoffs", "selling shares" and "drugs were ruled by FDA".Bo Jian, the "leader", has important implications for innovative drug enterprises of rare diseases in China.
Text | Zhang Yuqi Wu Ni
Editor | Yin Lina
Cartography | Li Ziya
March 28, 2022, Bojian
（BIIB.NASDAQ）
The treatment of amyotrophic lateral sclerosis is disclosed
（ALS）
The first-line results of the first-phase clinical trial of the antisense nucleic acid drug BIIB078 showed that the drug had no clinical benefit, so Bojian and Lonis decided to terminate their clinical trial and stop the loss in time.
（BIIB.NASDAQ）
The treatment of amyotrophic lateral sclerosis is disclosed
（ALS）
The first-line results of the first-phase clinical trial of the antisense nucleic acid drug BIIB078 showed that the drug had no clinical benefit, so Bojian and Lonis decided to terminate their clinical trial and stop the loss in time.
Prior to this, in 2016, Bo Jian also suffered from spinal muscular atrophy
(hereinafter called "SMA")
Therapeutic drugs usher in a high-light moment. However, the research and development of new drugs is a "narrow escape", and Bo Jian is not spared. In the past few years, he has repeatedly suffered setbacks in the clinical stage.
(hereinafter called "SMA")
Therapeutic drugs usher in a high-light moment. However, the research and development of new drugs is a "narrow escape", and Bo Jian is not spared. In the past few years, he has repeatedly suffered setbacks in the clinical stage.
According to media reports, a spokesman for Bojian said: "The company is implementing cost-cutting measures, and it is expected to save 500 million US dollars every year through layoffs."
The failure rate of research and development of Alzheimer’s disease is as high as 99.6%, which can be described as the defeat of Qian Fan. Since the 21st century, more than 320 clinical studies of global innovative pharmaceutical companies have failed. As a head biotechnology company in the field of neurology, Bojian is experiencing its "life and death field". Maybe the dust will settle before April 11th. Is Aduhelm still hopeful to be the next Nocicna sodium?
01
Ambition is hard to pay.
What can the Nobel Prize winners in chemistry, medicine and hepatitis B vaccine developers do together?
—— Established Bojian Company.
Bojian
（Biogen）
Born in 1978, focusing on the field of neuroscience. Its founder team can be described as a luxury lineup. In 1980, Dr. Walter Gilbert, one of its founders, won the Nobel Prize in Chemistry. In 1993, another founder, Dr. Phillip Sharp, won the Nobel Prize in Physiology or Medicine; Dr Kenneth Murray was also knighted for developing hepatitis B vaccine.
（Biogen）
Born in 1978, focusing on the field of neuroscience. Its founder team can be described as a luxury lineup. In 1980, Dr. Walter Gilbert, one of its founders, won the Nobel Prize in Chemistry. In 1993, another founder, Dr. Phillip Sharp, won the Nobel Prize in Physiology or Medicine; Dr Kenneth Murray was also knighted for developing hepatitis B vaccine.
Strong innovative genes, coupled with more than 40 years of precipitation and development, make Bojian gradually become a brother in the field of nervous system diseases, and in multiple sclerosis.
（MS）
Field and spinal muscular atrophy
（SMA）
Leading the way in the field.
（MS）
Field and spinal muscular atrophy
（SMA）
Leading the way in the field.
In 2013, fumaric acid II developed by Bojian
（Tecfidera）
Approved by FDA, it has become one of the most widely used oral drugs in the field of MS treatment in the world. In 2019, Tecfidera’s sales reached a peak of 4.433 billion US dollars. In the same year, an upgraded version of dimethyl fumarate, deloximet fumarate.
（Vumerity）
Successful relay, approved by FDA, has a place in the market with better gastrointestinal tolerance and safety.
（Tecfidera）
Approved by FDA, it has become one of the most widely used oral drugs in the field of MS treatment in the world. In 2019, Tecfidera’s sales reached a peak of 4.433 billion US dollars. In the same year, an upgraded version of dimethyl fumarate, deloximet fumarate.
（Vumerity）
Successful relay, approved by FDA, has a place in the market with better gastrointestinal tolerance and safety.
In 2016, Bojian developed the world’s first therapeutic drug for SMA-Nocicnatrium.
（Spinraza）
It has brought a major breakthrough to the field of rare diseases. With the first-Mover advantage, by the end of 2021, Nocicnatrium has brought nearly $9 billion in sales to Bojian.
（Spinraza）
It has brought a major breakthrough to the field of rare diseases. With the first-Mover advantage, by the end of 2021, Nocicnatrium has brought nearly $9 billion in sales to Bojian.
Noxinasen sodium and dimethyl fumarate
(deloximet fumarate)
Become two carriages, pulling Bo Jian to run faster and faster.
(deloximet fumarate)
Become two carriages, pulling Bo Jian to run faster and faster.
However, the good times did not last long. In 2020, huge hidden dangers surfaced.
The first is the patent of dimethyl fumarate.
Bojian once carried out a series of patent layouts for dimethyl fumarate, and strived to monopolize the market until 2028.
Bojian once carried out a series of patent layouts for dimethyl fumarate, and strived to monopolize the market until 2028.
But this is just Bo Jian’s wishful thinking. In February 2019, Mylan initiated a patent challenge to Bojian for dimethyl fumarate, and won the case, ending the exclusive period of dimethyl fumarate market ahead of schedule.
Subsequently, generic drugs flocked.
In China, there are 8 enterprises approved by CFDA, including Jiangsu Haosen, Jinan Bainuo and Hangzhou Heze. Under the impact of generic drugs, the performance of dimethyl fumarate in 2020 was $3.905 billion, down 12% year-on-year; In 2021, this figure dropped to $2.362 billion, a further drop of 39.5%.
In China, there are 8 enterprises approved by CFDA, including Jiangsu Haosen, Jinan Bainuo and Hangzhou Heze. Under the impact of generic drugs, the performance of dimethyl fumarate in 2020 was $3.905 billion, down 12% year-on-year; In 2021, this figure dropped to $2.362 billion, a further drop of 39.5%.
The field of SMA is also not very optimistic. Although the patent of Nocina sodium will expire in 2023, the competing products have already approached. Zolgensma of Novartis and Evrysdi of Roche/Genentech were listed in 2019 and 2020, respectively, which encroached on the market of Nocicina sodium. The sales of Nosina sodium decreased from $2 billion in 2020 to $1.9 billion in 2021, while the sales revenue of Zolgensma in 2021 reached $1.351 billion, up 47% year-on-year.
Secondly, the research and development is "green and yellow." In order to maintain its advantages in SMA and MS, Bojian has never stopped innovating.
Unfortunately, it failed to make a breakthrough as expected.
Unfortunately, it failed to make a breakthrough as expected.
In August, 2021, the research and development of multiple sclerosis drug opicinumab stopped in Phase II clinical trial, because the drug did not reach the primary and secondary endpoints in Phase II AFFINITY research. In January, 2022, Bojian introduced a global exclusive license of BiIB 115/Ion 306, a drug for SMA, from Ionis Pharmaceuticals. However, there is still a long way to go before it goes on the market.
Until now, Bojian has not waited for the next growth point, whether in SMA and MS fields or in new business fields.
The safety of Aduhelm, a highly anticipated drug for Alzheimer’s disease, has been controversial. According to Bojian’s 2021 financial report released on February 3, the sales of Aduhelm since its listing in June was only $3 million, far below expectations.
Gene therapy BIIB111 and BIIB112, non-opioid analgesic vixotrigine(BIIB074), antisense oligonucleotide drug tofersen, amyotrophic lateral sclerosis.
（ALS）
The candidate drug BIIB078 has successively declared clinical failure.
（ALS）
The candidate drug BIIB078 has successively declared clinical failure.
02
be bogged down in crisis
Repeated failures in research and development have made Bojian, which is based on innovative drugs, in danger.
The most intuitive feeling is that the performance has dropped significantly. In 2020, Bojian’s revenue was at the bottom of 14 multinational pharmaceutical companies. In 2021, Bojian hit a new low, and its revenue continued to decline by 18.3% year-on-year. The share price also hit a record low, falling by more than 36% from its August 2021 high.
Open source failed, and Bojian began to consider throttling.
In December 2021, more than 100 employees were dismissed, including two-thirds of the commercialization team of Aduhelm, a drug for Alzheimer’s disease. According to media reports in early March, Bojian may continue to lay off as many as 1,000 employees in order to save as much as $750 million.
Sadly,Senior executives who left Bojian synchronously with this layoff plan include AlfredSandrock, chief R&D officer of Bojian, and AlphonseGaldes, a veteran of Bojian who is responsible for global manufacturing.
In February this year, Bojian took its stake in Samsung Bioepis Company for as much as $2.3 billion.
(49.9% of the shares)
Sold to Samsung Bio. After the acquisition is completed, the two companies will continue to implement the exclusive agreement signed before, including the current portfolio
(Inaxip, adalimumab, Infliximab)
Commercialization. In addition, Bojian also has the exclusive right to commercialize rezumab and the biological similar drugs under research.
(49.9% of the shares)
Sold to Samsung Bio. After the acquisition is completed, the two companies will continue to implement the exclusive agreement signed before, including the current portfolio
(Inaxip, adalimumab, Infliximab)
Commercialization. In addition, Bojian also has the exclusive right to commercialize rezumab and the biological similar drugs under research.
Layoffs and the sale of shares, or helpless actions, have also started a downward spiral cycle.
Along the way, Bojian’s red and black are equally bright, both determined by the product. Drugs for neurological diseases have always been called the "death knell" in the field of medical research and development, and it is even more billowing in the field of Alzheimer’s disease, but it has little effect. More than 99% of the drugs end up in the dust, leaving behind "the best of the best".
As you can imagine, Bo Jian
（Biogen）
How difficult this road is.
As you can imagine, Bo Jian
（Biogen）
How difficult this road is.
In October last year, Bo Jian frankly announced amyotrophic lateral sclerosis.
（ASL）
Valor, the third phase trial of Tofersen, has entered the "end point", and the popular explanation is that this drug may eventually fail to develop. This is nothing new to the original drug.Failure is the accumulation of experience, and success is accidental victory.
（ASL）
Valor, the third phase trial of Tofersen, has entered the "end point", and the popular explanation is that this drug may eventually fail to develop. This is nothing new to the original drug.Failure is the accumulation of experience, and success is accidental victory.
Aduhelm of Bojian
(aducanumab, aducanumab)
That’s about it.
(aducanumab, aducanumab)
That’s about it.
American Association of Pharmaceutical Research and Manufacturers
（PhRMA）
According to the report data of,From 1998 to 2017, 146 drugs for Alzheimer’s disease have entered the "end point" of clinical trials worldwide, and only 4 drugs have successfully entered the market. In other words, only one out of every 37 drugs can be "successful".
（PhRMA）
According to the report data of,From 1998 to 2017, 146 drugs for Alzheimer’s disease have entered the "end point" of clinical trials worldwide, and only 4 drugs have successfully entered the market. In other words, only one out of every 37 drugs can be "successful".
However, the "success" of R&D is only the first step, and whether it can be introduced to the market still needs "going through five customs and cutting six generals".
On June 7, 2021, FDA announced that Aduhelm, a new drug for Bojian’s Alzheimer’s Harmo’s disease.
(aducanumab, aducanumab)
Approved for use. After the news came out, Bojian’s share price rose sharply. After all, the research and development of AD drugs is very difficult, and Aduhelm is the seventh AD drug approved by FDA in the past 30 years, and it is also the re-approval of drugs in this field after 7 years.
(aducanumab, aducanumab)
Approved for use. After the news came out, Bojian’s share price rose sharply. After all, the research and development of AD drugs is very difficult, and Aduhelm is the seventh AD drug approved by FDA in the past 30 years, and it is also the re-approval of drugs in this field after 7 years.
Although Bojian’s Aduhelm has been "recognized" by FDA, there have been many controversies, such as quarrels at expert meetings in the field, disapproval in markets outside the field, sales cliff, and even by the American Medical Insurance and Medicaid Service Center.（CMS）Restrictions.
During the seven-hour consultation meeting, various expert groups in FDA argued endlessly that "the relationship between amyloid protein in the brain and the pathogenesis of Alzheimer’s disease is uncertain". Neuroscientists and biostatisticians believe that Bojian’s experimental data are not valid and complete.
On the one hand, the expert group thinks that the FDA is suspected of harboring Bo Jian, and even three experts of the FDA Advisory Committee have resigned one after another, pointing directly at the FDA. They think that although the FDA pointed out the loopholes in biometric data, it still approved Bojian’s research and development drug-—Aduhelm in neurological review.
On the other hand, the Alzheimer’s Disease Association, the American Neurology Association and the International Alzheimer’s Harmo Disease Association expressed their support for Bojian’s new AD drug, and finally the FDA approved it.
03
Go on and on
Bo Jian, who is experiencing the storm of layoffs and the cliff of revenue, looks very embarrassed, but in fact, this is the only way to develop new drugs.
Compared with Bojian, those biotech enterprises that make false clinical trials and "pseudo-innovation" are the real "bubbles" in the ups and downs of the industry.
Compared with Bojian, those biotech enterprises that make false clinical trials and "pseudo-innovation" are the real "bubbles" in the ups and downs of the industry.
Industry insiders pointed out that "the phenomenon of nonstandard and incomplete data in drug clinical trials is still serious". As early as 2015, some clues were explored in the "July 22 verification storm" of the former State Food and Drug Administration. Among the 1622 drug clinical trials, more than 80% of new drug applications were withdrawn by pharmaceutical companies or "rejected" by the former State Food and Drug Administration.
Even multinational pharmaceutical company Merck
（MRK.NYSE）
Bristol-Myers Squibb
（BMY.NYSE）
It has also been revoked by the FDA.
（MRK.NYSE）
Bristol-Myers Squibb
（BMY.NYSE）
It has also been revoked by the FDA.
On July 2, 2021, a paper came into view.
National Medical Products Administration medicines evaluation examination and approval center
（CDE）
Issued the relevant technical requirements for pharmaceutical common problems at the pre-market application meeting of innovative chemicals.
(Draft for Comment)
"and" guiding principles for clinical research and development of anti-tumor drugs oriented by clinical value "
(Draft for Comment)
In this paper, a head-to-head clinical trial with the latest treatment scheme is put forward, especially for tumor drugs, and the commercialization differences of products are clarified.The industry calls it "combating pseudo-innovation". For a time, the road of innovative drug research and development seems to be narrowing.
National Medical Products Administration medicines evaluation examination and approval center
（CDE）
Issued the relevant technical requirements for pharmaceutical common problems at the pre-market application meeting of innovative chemicals.
(Draft for Comment)
"and" guiding principles for clinical research and development of anti-tumor drugs oriented by clinical value "
(Draft for Comment)
In this paper, a head-to-head clinical trial with the latest treatment scheme is put forward, especially for tumor drugs, and the commercialization differences of products are clarified.The industry calls it "combating pseudo-innovation". For a time, the road of innovative drug research and development seems to be narrowing.
Although the research and development of new drugs is a narrow escape, some people die young and some people are lucky, but we have to say that biological research and development is a "cause" that burns money now and in the future, depending on who can be strong in the end.
From 2016 to 2021, Bojian’s R&D investment increased steadily, reaching the peak in recent years in 2020, with R&D expenditure reaching $3.991 billion, accounting for 29.58%. However, in 2021, due to multiple factors such as the epidemic situation and the research and development of new AD drugs, the R&D investment declined, with an investment of $2.501 billion and a year-on-year decrease of 6.91%.
In this protracted "controversy", despite Aduhelm’s obstruction, Bojian never gave up. In mid-December, 2021, Bojian announced that it would carry out a clinical IV trial with its development partner Wei Cai, which is expected to be completed within four years after the start of the study. As part of the Phase IV trial, Bojian and Weicai plan to recruit 18% American patients from African-American and Latino populations. Bojian said that this move is also part of continuous efforts to increase the diversity of Aduhelm clinical trials.
At the same time, Bo Jian is still exploring in various fields of neuroscience. Bojian is used to treat amyotrophic lateral sclerosis.
（ALS）
The clinical trial of BIIB078, an antisense oligonucleotide drug under research, has been terminated. On the evening of March 30th, the FDA was holding a PCNSDAC meeting to discuss another new drug of ALS-AMX0035 of -Amylys. The FDA still questioned its effectiveness, and the result is still waiting.
（ALS）
The clinical trial of BIIB078, an antisense oligonucleotide drug under research, has been terminated. On the evening of March 30th, the FDA was holding a PCNSDAC meeting to discuss another new drug of ALS-AMX0035 of -Amylys. The FDA still questioned its effectiveness, and the result is still waiting.
For Bojian, the American Center for Medicare and Medicaid Services
（CMS）
The "final verdict" has not yet arrived.
(Time is before April 11th, 2022)
,It is unknown where Aduhelm can go. Can Bojian come out with the next SMA? Maybe it’s still on its way.
（CMS）
The "final verdict" has not yet arrived.
(Time is before April 11th, 2022)
,It is unknown where Aduhelm can go. Can Bojian come out with the next SMA? Maybe it’s still on its way.
Bi Jingquan, former director of the State Food and Drug Administration, said,
The high risk of innovative drugs should correspond to high returns.
.
(Click on the hyperlink to read the original text)
The high risk of innovative drugs should correspond to high returns.
.
(Click on the hyperlink to read the original text)
Faced with the high risk of a narrow escape, most people give up, but in clinic and market, if more people need to join, they need high-return opportunities. If the risk is high and there is no corresponding return, then who is willing to contribute to this biomedical industry with high failure rate?
(The author is a researcher at Caijing)