There is rarely a movie that can affect the nerves of more than one billion people in the country like "I am not a drug god" and let the Prime Minister give instructions. Behind this, in addition to the excellent production of the behind-the-scenes team and the acting of the actors, perhaps more important is the social reality reflected in the theme.
China is a big country with a large number of patients with various diseases.
China is a big pharmaceutical country, but it is not a pharmaceutical power.
China needs good medicine and needs medicine that patients can afford.
"At the time, I didn't read the movie "I don't want medicine", but the starting point was actually the same. I hope that useful drugs can enter China, and patients can afford it." Dinghui Investment President Jiao Zhen told the arterial network reporter.
In June 2018, CDH Investment and Yuanda Pharmaceuticals and Australian company Sirtex announced an agreement to acquire it for A$1.9 billion in order to introduce its liver cancer drug Y-90 into China. Prior to them, Varian Medical in the United States had reached an acquisition agreement with it. In order to enable this drug to enter China faster, CDH Investment and Yuanda Pharmaceutical made rapid decisions and acquired it at a premium of 20% compared with Varian.
China is a large country with liver cancer, but in the choice of treatment options, the number of alternative treatment methods is not as good as that of developed countries. The acquisition of CDH is undoubtedly giving more hope to tens of millions of patients with liver cancer.
Not a drug god, they have done something more meaningful than the drug god.
Thrilling, only 4 days from Varian’s acquisition vote when submitting the quotation letter
On May 3, 2018, CDH Investment (referred to as: CDH) trading team contacted the board of Sirtex Medical Limited (Sirtex) and submitted a non-binding indicative letter.
At this point, it was only four days before the shareholders of Sirtex voted to approve Varian Medical (Varian).
As early as January 2018, the company announced an agreement with Varian to agree to be acquired by Varian at a price of A$28.00 per share. According to the original plan, Sirtex will hold a general meeting of shareholders on May 7, 2018 to vote for the Varian trading.
The offer from CDH is A$33.60 per share, implying a 100% stake in Sirtex at A$1.9 billion, a 20% premium to the Varian offer.
On the second day after receiving the quotation letter, Sirtex announced that the general meeting of shareholders had been suspended, and the acquisition began to show a major reversal. During this period, Sirtex gave CDH an acceleration for a period of time, and then Dinghui and Hong Kong listed company Yuanda Pharmaceutical submitted a binding quotation letter.
On June 14, 2018, Sirtex announced the termination of the deal with Varian, and signed a new agreement with CDH/Grand Pharmaceutical to execute the deed. All directors recommended shareholders to approve the CDH transaction, and CDH and Yuanda teamed up to take back the drug from Varian and planned to introduce the drug to China.
What kind of medicine is this?
Headquartered in Australia, the underlying company Sirtex is one of the world's only targeted radiotherapy companies.
Dinghui acquired it at a premium of 20% higher than Varian, mainly because of the prospect of the company's core product Y-90 in the field of advanced liver cancer.
Image courtesy of CDH Investment
Sirtex's Y-90 resin microspheres are a targeted radioactive microsphere that you can consider as a therapeutic drug or as a medical device for interventional radiology, ie for selective internal use of liver cancer. Radiation Therapy (SIRT). This is a treatment that can be chosen when the patient is otherwise ineffective or intolerable.
Although this treatment has not yet entered China, in the developed countries and regions such as the United States and Europe, targeted radioactive microspheres (SIR-Spheres) have long been a common treatment. It is understood that SIR-Spheres has been used in 1,160 medical centers in more than 40 countries around the world, using a total of more than 86,000 courses.
Sirtex was founded in 1997 by a surgeon in Australia and is also the inventor of the Y-90 microsphere. After the company was founded, the surgeon pushed the product to FDA approval.
However, at that time no one promoted the product, after all, it was still a small company that was unknown. “It’s like a small brewery workshop. When a few well-connected people come to drink, they have a taste of self-entertainment.†Mao Yilei, chief physician and professor of hepatobiliary surgery at Peking Union Medical College Hospital, told the arterial network.
The first acquisition was made, and the company ushered in a historical turning point. The company was sold to a US company, and the buyer further developed the product after getting the product. Most importantly, the company promoted Y-90 for the first time. Under their efforts, Y-90 successfully went out of Australia and covered more than 40 countries including Europe, America and Asia (China and Japan). A major liver cancer country has not been covered).
How big is the existing market?
Sirtex is one of the two major companies in the world of targeted radiotherapy for cancer, and its main competitor, BTG, is a UK-based company that specializes in the production of targeted radiotherapy microspheres in Canada.
The biggest difference between the two is that because the BTG microspheres use a large proportion of glass materials, Sirtex's resin microspheres are lighter in weight, easy to disperse and more operability.
BTG's approved markets include Canada, the United States, South Korea, Singapore, Saudi Arabia, Turkey, and parts of Europe, accounting for approximately 45% of the global radioactive embolic industry, but BTG is currently approved for hepatocellular carcinoma in the United States ( Treatment of HCC).
Image courtesy of CDH Investment
Sirtex has a global market share of 55% and has the highest market share. Sirtex's main markets are in North America and Europe, as well as Asian countries and regions including Singapore, Hong Kong, China and Taiwan. In Asia alone, Y-90 has been used more than 900 times since 2010, with a total dose of more than 3,400 in Asia.
According to the 2017 annual report of the two companies, BTG's total drug sales for the year was about 420 million US dollars, of which TheraSphere product sales revenue was 133 million US dollars, while Sirtex's total sales amounted to 234 million US dollars. The sales revenue of similar products is 100 million higher than BTG!
a bigger market, actually in China
Compared to PD-1/PD-L1, the so-called “magic medicineâ€, the current sales volume of Y-90 is not high. However, it should be noted that the current indications for Y90 approval are only a small part, and Europe and North America are not the most common areas of liver cancer.
The biggest market is actually in China.
Professor Mao Yilei told the arterial network that in the late 1990s and early 21st century, China’s hepatitis B carriers accounted for nearly 9.9% of the total population. In short, nearly one-tenth of the people of the country are carriers of hepatitis B.
"This number is scary." He described it like this.
Since 1992, the country has planned hepatitis B vaccine as a type of vaccine and has begun to spread among infants and children. Prevention is the most effective means. By April 2008, the index released by the Ministry of Health showed that the proportion of hepatitis B carriers in the entire population of China has dropped to 7.18%.
"This decline is very exciting. This is the number of previous years, and the number should be more optimistic now." Professor Mao Yilei told the arterial network.
However, he also stressed that the decline in the carrier's share does not mean that China has begun to take off the hat of the big country of liver disease. Although in younger groups such as children and adolescents, the hepatitis B carrier rate has dropped below 1%. However, in the population over 45 years old, the carrying rate is still high.
After the hepatitis B infection occurs, the patient may gradually develop liver fibrosis and cirrhosis, and then continue to deteriorate and may develop into liver cancer. As we all know, China is a big country with liver disease. According to the data released by the World Health Organization in 2014, about half of the new annual liver cancer patients in the world are in China.
"That is to say, if there are 20 new cases of liver cancer in the world, then China will account for 10 cases. What kind of number is this?" He could not help but sigh.
Therefore, after 26 years of hard work, our country has achieved very high results in the control of hepatitis B. But overall, the hepatitis B carrying rate in our country is still very high, and the incidence of liver cancer is still the highest in the world.
"The hat of a big country with liver disease is still firmly worn." Professor Mao Yilei emphasized.
It is a challenge and an opportunity
The World Bank has funded a 10-year research project in China with the main purpose of observing the burden of 10 chronic diseases on society. These chronic diseases include AIDS, tuberculosis, hepatitis, cirrhosis, and liver cancer. The final data shows that among these chronic diseases, the biggest burden on society is liver cancer, and the fourth is hepatitis B.
But opportunities always coexist with challenges, and opportunities often hide opportunities. "China has the largest population of liver cancer, and we should have the most say in the treatment plan and effect evaluation." Professor Mao Yilei said.
Clinical liver cancer solution
Liver cancer is an occult cancer that does not feel any pain in the early stages. Therefore, when the condition is discovered, it usually enters the middle and late stage of the tumor. "For liver cancer, the most important thing is early prevention and early diagnosis. Prevention is the most effective and economical," said Professor Mao Yilei.
Usually, 45-year-old males or hepatitis B-infected women over 50 years of age need to have a liver cancer screening every six months. If liver cancer is found early, it can usually be solved by simple treatment such as topical treatment or ablation treatment. However, if you wait until the middle and late stages, the treatment of liver cancer becomes diversified and complex, and the effect will be relatively poor.
At present, there are many treatment methods for liver cancer, and there are about ten ways to accumulate. Among them, surgical resection is ranked first. "This is universally recognized and there is no controversy," he stressed.
After the operation, if there is local residual tumor or recurrence, it will be clinically killed or controlled by local treatment such as intervention or ablation technique. .
These are two treatment regimens that are often used and can be used in conjunction with surgical treatment.
But tumors are a special type of disease, and it is difficult to prevent recurrence. When the tumor recurs, in addition to the above-mentioned interventional and ablation treatments, systemic treatments such as targeted therapy, immunotherapy, radiation therapy or chemotherapy can be selected. But these treatments are not perfect, and there is room for new treatment options. .
The emergence of Y-90 can provide more options for the treatment of advanced liver cancer.
What can Y-90 do?
Y-90 This is a selective intra-local radiation therapy. Y-90 is an isotope of metal ruthenium and is a kind of radioactive particle. Y-90 is coated with a layer of metal isotope on a tiny resin microsphere. Under the guidance of the microsphere, radioactive elements can enter the microvessels of the distal end and penetrate into the tumor to generate radioactive energy to kill the tumor cells.
Image courtesy of CDH Investment
For patients, this treatment is less invasive and is an interventional treatment: a tiny catheter is inserted from the femoral artery that extends all the way to the blood vessels that govern the liver tumor. "Then, all the blood vessels outside are sealed, and the microspheres containing radioactive substances are dispersed into the tumor body." Professor Mao Yilei introduced the reporter.
In addition to being a topical treatment after surgery, since liver cancer is an occult cancer, many patients have often missed the best period of surgery. Therefore, Y-90 may also be the treatment of choice for some patients.
"This is not the only option, but it may be one of the most important treatment options for liver cancer patients at some stage," he said.
Varian believes that on the basis of the existing, Y-90 can also develop new indications, including new combination therapies.
“The space here is very large.†Jiao Zhen said, “This company has been somewhat stagnant in the past few years due to management changes, etc.†But it’s the potential of the product that makes Varian and Dinghui rushed to throw high prices.
According to Jiao Zhen, in addition to the existing indications, they will try to conduct treatment research at different stages of the same cancer to explore whether this product can be applied to the treatment of early cancer. "The other is another similar advanced cancer that is theoretically feasible and will be tried later," he added.
Another feature of the product is that it does not affect other treatment options and facilitates combination therapy. “Before an expert in the United States suggested combining with CAR-T (or antibody), it might work better.†He introduced to the arterial network, “but this is only a directional study.†In the future of cancer treatment, There will be a variety of comprehensive treatments. Due to the particularity of Y-90, it may become an important part of future combination therapy. The current clinical research results also support the combination of Y-90 and chemotherapy, the effect is better than chemotherapy alone.
Born more than 20 years, never copied
In addition to efficacy, another advantage of Sirtex is its technical barriers. Y-90 has been born for more than 20 years, but has not been successfully copied.
In 2017, Sirtex's share price had a big drop. The reason behind this is that there is a new drug in Europe that has a very good effect on the treatment of liver cancer and is expected to replace Y-90. The results of the investigation showed that the effect of this new drug was not as good as Y-90, and the side effects were much larger. Sirtex's share price quickly rose.
"This product has faced several threats, but so far, no product has been able to replace it." Jiao Zhen said, "The effect is immediate."
First introduced by doctors in China
In fact, long before the commercial companies and capital participation, the domestic doctors have already seen the bright spots of the Y-90 and tried to introduce them into the country.
The earliest contact was with Academician Liu Yunyi. After the founder of Sirtex invented the technology, he found his friend Liu Yunyi in the first time. Under the efforts of the two, Y-90 passed the FDA approval. Liu Yunyi then returned to Hong Kong to use the technology to treat primary liver cancer.
Many years later, experts such as Ye Shenglong and Mao Yilei, directors of liver cancer at the Zhongshan Hospital of Fudan University Medical School, decided to try to introduce them to benefit Chinese patients after they came into contact with the products. It can be said that before CDH, these doctors have spontaneously promoted them from the perspective of medicine and patients.
"Now the awareness of this therapy in the doctor community is already high," he replied. However, at that time, the SFDA did not accept the clinical trial data of the drug. The time has passed seven or eight years, and no significant progress has been made.
However, at that time, even after the successful introduction of the products by doctors, the Y-90 was an imported product, and its pricing would not be low. The average price per dose in the US is close to $20,000. If imported by imported drugs, the price will be high or low.
After the acquisition, CDH will leverage Sirtex's roots in Australia to accelerate the growth of Sirtex in its core business markets (US, Europe and Australia) and to promote Sirtex products to areas where there is currently no business, especially in Asia. market.
In terms of introduction speed, under the impetus of capital, the speed of Y-90 entering China must be much faster; and in terms of patient cost, after the localization of products, it is bound to decline. This will be a boon for Chinese patients.
Arterial Network learned from CDH Medical that in the future the Chinese market will first use the products produced by Sirtex in Singapore, and local production in China is also planned.
Rationality or sensibility, where is the premium of a 20% premium acquisition?
In the announcement of the trading agreement with Sirtex, CDH actually faced a lot of public opinion pressure, and was shackled by the foreign media. After communicating with CDH and Professor Mao Yilei, Arterial Network believes that this premium transaction has some sentiments and impulses, but in fact it is more emboldened and courageous.
Liver cancer is one of the biggest causes of death in China, and China accounts for half of the world's liver cancer patients. However, from the current point of view, however, the current mainstream treatment methods in China have limited utility, and the number of alternative treatment methods is not as good as that of developed countries.
The entry of Y-90 will provide more choices for hundreds of billions of patients, which will prolong the patient's life cycle and improve the quality of life of patients. Not only that, Dinghui also revealed that after the product successfully entered China, its price will also be lower than that of the US.
"If they are acquired by foreign companies, they may not pay attention to the Chinese market in this way." Jiao Zhen said. In addition to making patients available, they also hope to make Y-90 a more affordable medicine.
From a commercial point of view, a purchase of 20% higher than Varian is actually a rational move for CDH. At present, Sirtex covers almost all regions of the world except China and Japan, and the United States is the main market.
As mentioned above, China is the world's largest market for liver cancer and a market that Sirtex has not yet entered, which means that more than 50% of the market has not yet been covered. After the completion of the acquisition, Sirtex will shift its focus to the Chinese market. Enter the work.
Once in the Chinese market, Sirtex's Y-90 products will benefit at least 355,000 liver cancer patients in China. The import registration will be followed by localization, and the localization of Y-90 can significantly reduce production costs. On the other hand, it will greatly reduce the logistics cost of radioactive products, which will greatly reduce the patient's medical burden.
According to the pricing of foreign Y-90 surgery, the corresponding domestic market total is about 150 billion yuan. If the market penetration rate can reach 5% in the future, the annual potential income can reach 7.5 billion yuan, which is the company's 2017 annual income. 7 times as much. CDH hopes that Sirtex will significantly reduce its cost in the next few years through localization. Sirtex will still be able to bring enough growth to China's growth in the case of a 50% reduction in foreign prices, but China's liver cancer patients will benefit from it.
“Varian did not consider the Chinese market, they also gave a very high price.†Jiao Zhen explained, “The Chinese market is worth 20%.â€
In addition to the rapid benefit of Chinese patients in the short term, Dinghui also has a platform for Sirtex's globalization. Currently, it has entered more than 1,000 medical centers worldwide. "This kind of global network is very difficult to get." Jiao Zhen said, "On such a global platform, if China has any original products, I think it can be pushed up."
After the transaction is completed, CDH will work with the partner Yuanda Pharmaceutical to launch the start-up plan for the products in China and Japan. The two parties will bring new resources for the company to enter the Chinese market, in the company management, capital market operation and It has helped the industry to accumulate knowledge and did not have a dedicated team of experts to enter the Chinese market.
"Yuanda Pharmaceutical has a very strong business and sales team throughout the country. They will provide a lot of support in the event of landing," said Jiao Zhen.
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