Challenging $ 1 billion in sales: Why are these areas likely to produce blockbuster drugs?

Source: Medical Network
The first thing domestic companies want to do to build a "blockbuster" drug is the R & D level problem, and the second thing that is also necessary is the enhancement of global marketing capabilities. In the last century, whenever one or a number of important targets were discovered and confirmed, it would be accompanied by the birth of a batch of "blockbuster" drugs. Reflect directly. So, what are the current major areas for blockbuster drugs, and where is the next area where blockbuster drugs will be born?
01 The hottest tumor market?
In 2018, there were 141 brand products with global sales exceeding one billion US dollars. Anti-tumor drugs are still regular customers with “billion” US dollars in sales, with 36 products exceeding one billion in sales, 12 for monoclonal antibodies and 8 for teni. The largest product in the market is lenalidomide, followed by PD-1 nivolumab.
Lenalidomide is the first-line and second-line drug recommended for multiple myeloma (MM, multiple myeloma) guidelines at home and abroad, and maintenance and continuous medication is preferred. It is the main therapeutic drug. Multiple myeloma is a hematological malignancy. According to data from the International Myeloma Organization (Myeloma.org), there are about 750,000 patients with multiple myeloma worldwide. GLOBOCAN 2018 reports that there are 20066 new MM patients in China every year. According to the above data, we can initially estimate that the total number of patients with multiple myeloma in China exceeds 100,000. If 100,000 people receive standard treatment, the epidemiology estimates that the size of the entire myeloma drug market can reach 10 billion yuan.
However, the sales of lenalidomide in China are average. In September 2017, Xinji transferred all of its three anti-cancer product operating rights including lenalidomide to BeiGene. BeiGene's 2018 annual report shows that the total net income of the three products in 2018 was USD 131 million. This is mainly because lenalidomide was approved for listing in January 2013, but was included in the national medical insurance negotiation list on July 13, 2017, and the market growth of non-medical insurance before 2017 was limited. After entering the medical insurance, the original research price was also adjusted from 2799 yuan (25mg / capsule) to 1101.99 yuan (25mg / capsule).
In November 2017, Shuanglu Pharmaceutical's generic drug was listed. In 2018, Shuanglu Pharmaceutical's annual report did not mention the full-year sales of the drug. Only in the 2018 semi-annual report, lenalidomide's sales revenue in the first half of 2018 was 4,800. More than ten thousand yuan. In 2019, another company Zhengda Tianqing and Qilu's generic drugs went public, and the product officially entered a price war. Shanghai Sunshine Pharmaceutical Purchasing Network announced on June 6 that Qilu's lenalidomide purchase price was 189.5 yuan (25mg / capsule). Zhengda Tianqing will lower the net price of nalidamine in Shandong Province to 188 yuan (25mg / capsule) on June 13. Although lenalidomide has not entered the second batch of volume purchase catalogs, with the increase in the number of manufacturers passing the consistency evaluation, it is expected that lenalidomide will be difficult to rebuild the glory of global sales in China. It can be described as "heavy foreign, domestic dismal".
PD-1 faces severe homogeneous competition in China and each of them has already developed expansion strategies to accelerate the development of indications, multi-target R & D, and joint drug development. However, the 2019 transcripts show that foreign-funded enterprises have achieved quite a lot in China. For example, Merck's PD-1 monoclonal antibody drug Keytruda (Pabolizumab) has been sold in China and has exceeded 2 billion yuan in domestic sales. Correspondingly, the sales revenue of PD-1 Sintilizumab in the first half of 2019 announced by Cinda in the semi-annual report for 2019 was 332 million, which shows that the blockbuster abroad and domestic metoo / mebetter drugs have the domestic In the market with home field advantage, domestic products may not be able to occupy the home field advantage, even if Xindili mAb is sold by Eli Lilly.
In addition, on the official website of the Medical Insurance Bureau, the list of "Negotiation of drugs during the agreement period (1) Western medicine" list, only PD-1 monoclonal antibody was shortlisted. From 7838 yuan (10ml: 100mg / bottle) to the medical insurance payment standard of 2843 yuan (10ml: 100mg / bottle). It is expected that the annual treatment cost of Xindilizumab will be reduced from RMB 160,000 to RMB 100,000 per donation plan.
It can be seen from this case that when the domestic drug market's approval and listing speed is becoming more and more in line with foreign markets, domestic metoo / mebetter new drugs have not been able to PK off imported pharmaceutical companies at home, let alone Chinese products want to be abroad The market won the competition and became a blockbuster.
Want to become a blockbuster in the field of tumors, first of all, this indication has a large number of people and there is no better medicine, such as small cell lung cancer. Secondly, it has sufficient clinical evidence to show that the efficacy of this product has advantages over products with similar targets, which requires the accumulation of a large amount of clinical trial data. Finally, global marketing capabilities are required, especially if the product is to be marketed in the United States as much as possible-although the tumor market in China is very broad, the anti-tumor drugs with annual sales revenues in the domestic market of more than 6 billion yuan are basically absent. Some indications with good global sales but general domestic sales need to be marketed in the United States, such as rheumatoid arthritis, psoriasis and other immune system medications.
02 Traditional chronic disease market
A total of 13 products for diabetes drugs are still blockbusters, of which 7 are insulin, 2 GLP-1, 2 DDP-4, 1 SGLT-2 inhibitor, and 1 DDP-4 + metformin. Insulin is not easy to imitate, original research products can maintain high sales for many years, and products with new mechanisms and more clinical advantages than existing products still have the opportunity to gain blockbusters.
One of the two exclusive products with annual sales of western medicine in China exceeding RMB 6 billion is Novo Nordisk Insulin Aspart. If the bombshell wants to maintain a long life, it must establish technical thresholds that cannot be easily copied.
Among traditional medicines, three original products of hypertension have sold over one billion US dollars, namely amlodipine, valsartan, valsartan + amlodipine. The original research income of amlodipine comes from the contributions of China and Japan. With the implementation of volume procurement in China, the global market size is also expected to be affected.
Hypertension can sell more than one billion basically expired original research drugs, but if there is a new drug with more clinical advantages and better safety, the new drug is expected to replace the market that has obtained blockbusters, and it will be a new drug from diabetes. Still gaining the status of blockbuster can confirm that traditional chronic diseases have new target mechanisms and have clinical advantages over already marketed drugs. It is not difficult for new drugs with new mechanisms and new drugs to produce "billion" blockbuster products. Big.
03Multi-mechanical compound preparation
There are 10 HIV antivirals with more than US $ 1 billion in total, five of which are from Gilead and are all fixed-dose combination preparations, such as emtricitabine + tenofovir alafenamide, emtricitabine + tenol Fouviravira + Ripivirin, Emtricitabine + Tenofovir Fumarate. The product with high hopes for this new crown epidemic, Red Desivir, is also from Gilead. It can be seen that Gilead has accumulated in the field of HIV, and Gilead has a large number of antiviral compounds before it can play the compound combination.
In the respiratory field, such as chronic obstructive pulmonary disease, six products also entered the "billion dollar club", of which AstraZeneca and GlaxoSmithKline each accounted for two. AstraZeneca's budesonide also has RMB 6 billion in revenue in China, and its indications are not only chronic obstructive pulmonary disease, but also asthma, allergic rhinitis, and so on. Chronic obstructive pulmonary disease also has three fixed-dose combination formulations in excess of $ 1 billion.
Hepatitis C products total 3 products over one billion US dollars, all of which are compound preparations, 2 of which are from Gilead and 1 from AbbVie.
Clinically, a variety of indications are required for simultaneous treatment with different mechanisms. The development of fixed-dose combination formulations with the same medication route can improve patient compliance. However, this requires that the patient has already taken one of the unilaterals, which means that this unilateral or else is a first-line routine. Medication, or else the company has a strong market ability for most patients to take their own products. In addition, it is best for companies to have patent rights on the chemical ingredients and corresponding indications in the composition to avoid the risks of generic drug manufacturers and competitors' imitation.
04 Several key areas for blockbusters
1) Alzheimer's disease (AD)
Dementia is a group of acquired intellectual impairments with cognitive impairment as the main clinical manifestation and psychiatric behavioral symptoms that lead to a decline in the ability of daily living due to a variety of reasons. It is more common in the elderly. The most common type is Alz Hemer disease (AD), followed by vascular cognitive impairment or dementia. At the end of 2013, China's population over 65 years of age had reached 132 million. According to estimates of the prevalence of dementia of 7.8% and the prevalence of AD of 4.8%, there are about 10 million dementia patients in China, of which about 6 million are AD patients.
In the broad sense of dementia, there are 44 million AD patients worldwide, and an estimated 604 billion U.S. dollars in medical costs (including the cost of medical staff, nursing staff, etc.) each year. In developed countries, Alzheimer's disease is one of the main diseases that consume social financial subsidies. Taking the United States as an example, Alzheimer's disease is the sixth leading cause of death, with a confirmed case every 66 seconds; and the annual cost of the entire society is as high as US $ 259 billion.
Due to the huge burden of Alzheimer's disease on patients and society, and currently no effective treatment is available, the currently approved drugs are drugs that slow the clinical symptoms of Alzheimer's disease.
Since 2002, pharmaceutical companies have invested more than 200 billion US dollars in the development of new AD drugs. However, in more than 200 clinical studies, only one AD drug has been successfully marketed, and the failure rate of drug development has reached 99.6%. The reason for the failure of drug development is that the above drugs were developed based on the amyloid theory. The amyloid theory suggests that the accumulation of amyloid beta in the brain is the cause of dementia and cognitive impairment. However, biological genetic tests and many other drug trials to prevent or eliminate amyloid have shown that even in patients with early-stage Alzheimer's disease, cognitive performance has not improved.
Unclear pathogenesis, complex onset causes, long duration, and hidden onset are the main dilemmas of current AD drug development. However, as long as any company in the world can develop a drug that slows the progress of AD, it will be a "super blockbuster."
2) Non-alcoholic steatohepatitis / liver fibrosis
The potential for medications for nonalcoholic steatohepatitis (NASH) is huge. NASH is often caused by obesity and belongs to a fatty liver disease. More than 16 million people have the disease in the United States alone. In addition, non-alcoholic fatty liver disease (NAFLD) is a threatened disease characterized by high levels of liver fat and may affect approximately 80 million people in the United States.
The incidence in China has also been increasing in recent years. Epidemiological surveys from Shanghai and Beijing have shown that the prevalence of NAFLD diagnosed by B-mode ultrasound in ordinary adults has increased from 15% to more than 31% in 10 years. Liver biopsy confirmed that NASH accounted for 41.4% of patients with NAFLD and cirrhosis accounted for 2%. It is reported that there were approximately 240 million NAFLD people in China in 2016. By 2030, the NAFLD population is expected to increase to approximately 310 million, of which patients with liver cirrhosis will reach approximately 2.3 million.
The main known causes of NASH include metabolic syndrome such as obesity, type 2 diabetes, hyperlipidemia, and hypertension. However, the industry's diagnosis of NASH still relies on liver biopsy assessment, and no therapeutic drug for this indication has been approved for marketing globally. For the purpose of treatment, it is mainly to control the progress of related diseases such as obesity, type 2 diabetes and hyperlipidemia, and weight management is usually selected as the first treatment plan for NASH.
In recent years, NASH new drugs have become a new hot spot in the industry, and the industry believes that its market potential is 35 billion US dollars. The battle of NASH between domestic imported pharmaceutical companies and domestic pharmaceutical companies is likely to be similar to the situation of the PD-1 war. There is always a first-mover advantage if it is listed first, but only if it can be successfully listed in China.
3) Ischemic stroke
Ischemic stroke is a blockage of blood supply to the brain caused by a variety of causes, leading to limited or comprehensive brain function and / or structural damage, including transient ischemic attack (TIA), cerebral infarction, and cerebral embolism. Stroke is China's first cause of death.
There are more than 7 million stroke patients in China, ranking first in vascular diseases. One to two million new cases are reported each year. The annual incidence of stroke after adjusted age is (116-219) 100,000, and the annual mortality rate is (58-142) 100,000. Among the survivors, 70- 80%.
The treatment of acute ischemic stroke is mainly based on conservative drug treatment, and its treatment strategies are mainly focused on the following two aspects: one is the treatment for the purpose of improving cerebral blood circulation, and the other is the use of neuroprotective agents to protect the structure of nerve cells And functional treatment. However, the choice of drugs for these two treatment strategies in clinical practice is very limited.
Measures to improve cerebral blood circulation include thrombolysis, antiplatelet, anticoagulation, defibrillation, and volume expansion. In 2018, a total of 6 products entered the "billion club". Currently, the only effective treatment for ischemic stroke is rt-PA thrombolysis, but due to its strict time window, indications, and contraindications, less than 1% of patients in China are eligible for rt-PA thrombolysis.
Neuroprotective agents used in the treatment of stroke in our country include edaravone, nimodipine, and ciprazide maleate. Although neuroprotective agents have been used to treat acute ischemic stroke for more than 30 years, the clinical results accumulated over the years have been disappointing. With the domestic control of neuroprotective agents as key monitoring drugs, the market of neuroprotective agents in China will decline in the future.
In summary, if drugs that are better than those available for the treatment of acute ischemic stroke can be developed, the drugs that can be treated in this field are limited and the possibility of becoming a blockbuster is very high.