Author: Liang Jialin
A new generation of "magic drugs" - immunological tumor PD-1 treatment drugs officially listed in China this week. Pharmaceutical giants have to set off a "war of time" in a very limited market monopoly, grab pricing benchmarks, grab market capacity, and grab sales channels.
From August 28th, the first PD-1 anticancer drug Opdivo (Chinese name “Oddivo”, commonly known as O medicine), which was approved for listing in China, was officially launched in more than 50 cities in China. On the 29th, Hubei, Anhui, Henan, Shanghai and other places have successively issued the first prescription for local immunotherapy. It is rumored in the medical circle that the first-day sales of O-pharmaceuticals exceeded 100 million.
Although the authoritative source of this data is not testable, the head of the relevant department of Bristol-Myers Squibb (BMS) China has replied to the health point that it will not be commented. However, it is undeniable that as the anti-cancer "magic medicine" that pioneered the revolutionary treatment of cancer treatment, even if the patient still bears the expenses at his own expense, the demand for clinical outbreak is obvious. And the previous "Shenzhen" Gleevec has set off a series of storms such as overseas drug purchases and Lu Yong's arrest. This time, the O-pharmaceutical pricing and circulation strategy for landing in China will not give the drug gods overseas purchases. Opportunity. According to Liu Qian, a medical marketing expert, BMS has set the price of medicines to be only two-thirds of Hong Kong, China, and far below the US domestic price. Goldman Sachs Consulting even predicts that this will give birth to a wave of “medical tourism” opportunities for overseas patients to come to China for immunotherapy.
However, medical industry experts interviewed by health points agreed that as the competing products in the same industry followed the listing, it is assumed that the approval efficiency of expanding the indications remains at the level of “Bijingquan period”, and O medicine is the first immunotherapeutic drug in China. The market monopolization period is less than half a year. In response, BMS companies need to speed up the approval of O-drugs for indications other than non-small cell lung cancer; on the other hand, they need to speed up the layout in DTP pharmacies and medical insurance access. At the time of writing, the person in charge of the relevant department of Bristol-Myers Squibb China said that it would not comment.
For cancer patients, more immune tumor (I-O) treatments are both a puzzle and a gospel. On the one hand, this increases the decision-making cost of patients choosing different drugs. The key point is which patients who are more precise in patient “stratification” and achieve precise personalized treatment, thus improving the response rate of immunotherapy only 20%. On the other hand, this is conducive to reducing the cost of purchasing drugs for patients. The drugs that are listed on the market need to comply with the relatively low price benchmark established by O medicine, and achieve competitive in the process of access to basic medical insurance and commercial insurance. Sub-price reduction.
Pricing: lower than expected, expected to cut prices twice
On June 15, the State Food and Drug Administration (CNDA) announced that O medicine has become the first monoclonal antibody to target PD-1 in China. Yin Wei, CEO of Huada Gene, commented in a circle of friends that if O medicine can set the price at one-tenth of the US, that is, 100,000 yuan/year, the national basic medical insurance should be very happy to cover, but the possibility is very low. At that time, he predicted that the price of O medicine in China was between RMB 400,000 and RMB 600,000.
Yin Wei only guessed half of it, O medicine did not include health insurance for the first time, but the price is still lower than market expectations. On August 20th, BMS announced the pricing system, which allowed an investor in Yikai Capital to call out “how many (the pharmaceutical companies) comrades’ model assumptions should be torn off and rearranged”. The suggested retail price of O medicine is set at 100mg/10ml 9260 yuan; 40mg/10ml 4591 yuan. Patients with different body weights have different amounts of guidance. For example, in a 50 kg patient, intravenous injection is performed once every two weeks, and one 100 mg/10 ml and two 40 mg/10 ml are used at a time.
Therefore, the industry ridiculed "O medicine theory to sell". Some people have calculated it by themselves. According to BMS's recommendation, the monthly medication cost for a 50kg body weight patient is about 27,000 yuan, while the 80kg body weight patient's medication cost is about 46,000 yuan per month.
Before announcing the appointment of AstraZeneca as China's vice president, Liu Qian, a pharmaceutical marketing expert, commented on the O-pharmaceutical pricing strategy, saying that BMS's suggested retail price is almost one-third cheaper than Hong Kong. This shows that the manufacturer responded to the government's call and complied with the trend since the performance of "I am not a drug god", and set a global "floor price". A monoclonal antibody product that requires a cold chain is even lower in price than a small molecule targeted drug, and it needs to be in the top three in the next immune-tumor (I-O) therapeutic drug war.
Liu Qian even believes that the rhythm of several companies listed and approved, "deliberately avoided" the anti-cancer drug medical insurance drug access negotiations organized by the National Medical Insurance Bureau. A number of pharmaceutical industry experts told health points that O medicine is currently in the market exclusive period of the immune tumor (IO) treatment competition. Instead of accepting medical insurance negotiations to passively reduce prices, it is better to take the initiative to control the price reduction rhythm, so let the published price time dragged through June 31 Japan. The deadline for the round of medical insurance price negotiations is a wise choice.
Idea Di CEO Gong Zhaolong told the health point that the price of O drug is the first time in the world that the hot-selling Chinese imported drug is far lower than the developed countries in Europe and America, reflecting the efforts of the government, especially the National Health Insurance Bureau, to lower the price of drugs. Play the effect. BMS has received very good positive feedback from the “price-for-price” strategy. The first day sales were very large, and some regions even experienced short supply, which made the global headquarters more motivated to distribute more drugs to China and put more marketing. Resources to meet the needs of Chinese cancer patients.
Gong Zhaolong believes that the price benchmark is significantly lower than expected, which will help to quickly seize patients in the market exclusive period. Because patients with advanced and metastatic non-small cell lung cancer use O drugs, they will not easily switch to other immunotherapeutics, and BMS will join the relevant agencies to launch charitable drug-donating programs, which will further improve patient loyalty.
A number of interviewed experts said that, in view of the surrounding market, as the patent period expires, the competitive products of the same indication are listed, in order to maintain a high market share, the price of O medicine can only choose to cut prices twice. Take the developed country market in Japan as an example. Since the 100 mg bottle was launched in 2014, the price of O medicine has dropped from 730,000 yen just listed to 278,000 yen in March 2018. It is expected to fall to 17.4 in November. Ten thousand yen.
Another way to maintain a high enough market share is to access the commercial insurance system. The PD-1 immunotherapy drug listed immediately after the O drug is the pembrolizumab monoclonal antibody (commonly known as K drug) of Merck (MSD). The market is expected to be available in September. Merck (MSD) has revealed that K medicine has joined China Ping An Insurance's first catalogue of new drug-preserving tumors in China - "Safety Insurance New Drugs Catalogue". Of course, the amount of insurance for commercial insurance is much higher than that of basic medical insurance.
As a former senior reviewer of the US Food and Drug Administration (FDA), Gong Zhaolong believes that the first indication for K drug in China is systemic treatment of advanced melanoma, unlike advanced and metastatic non-small cells of O drug. Lung cancer, therefore, the introduction of super-indications in specialized hospitals such as chest hospitals and pulmonary hospitals in the early stage will be hindered. However, Gong Zhaolong believes that K-medical non-small cell lung cancer and other large indications are also accelerating the listing, and the National Bureau has launched the acceptance of overseas clinical trial data as a basis for reporting the policy of supporting domestic listing. O-drug may only be in the market for large indications. Half a year. Gong Zhaolong compared FDA experience, the fastest time for FDA to expand the indication is 4 working days.
At the same time, domestic PD-1 immunotherapy drugs are also on the way to the road. As of August this year, three Chinese pharmaceutical companies have submitted new drug listing applications to the State Food and Drug Administration (CFDA), all of which are immunotherapeutic drugs of the same type as O drugs. They are: Shanghai Junshi (indications: melanoma), Cinda (Hodgkin's lymphoma), and Hengrui Medicine (Hodgkin's lymphoma). Cinda Biology and Baekje Shenzhou have entered the clinical trial phase 3 with immunotherapy drugs for non-small cell lung cancer.
Market: Opportunities and risks of over-indications
Li Dinggang, executive director of Lu Daopei Blood Hospital, said that with the listing of O medicine in mainland China, “the emergence and clinical application of an innovative drug will definitely bring about an innovative diagnosis and treatment system, especially in the era of biological immunotherapy.” Li Dinggang said that when medicine is available, doctors are extremely important factors in how to diagnose and formulate medication regimens. Just as China originally had its own aircraft carrier, but lacked the carrier commander. For most oncologists in mainland China (inland), PD-1 is a new drug, with insufficient experience in drug administration, and has not dealt with the experience of related side reactions brought about by the use of PD-1.
The doctor's prescription right not only determines the quality of life of the patient, but also determines the market size of the O drug. At present, O-medicine approved indications in mainland China specifically refer to advanced or metastatic non-small cell lung cancer (NSCLC) that meet specific conditions. Chen Xiaodong, director of the Propaganda Department of the Chinese Affairs Department of the US-China Medicine Association, said that in foreign countries, O-drugs have been approved for a variety of indications, covering melanoma, non-small cell lung cancer, kidney cancer, Hodgkin's lymphoma, head and neck cancer, bladder cancer, Colorectal cancer, liver cancer, gastric cancer and other tumors.
In February 2018, the latest national cancer statistics released by the National Cancer Center showed that in 2014, the number of new cases of malignant tumors in the country was estimated to be 3.804 million, and lung cancer ranked first in the national cancer, with an annual incidence of about 781,000. Gong Zhaolong believes that a large number of patients with failed first-line treatment will receive second-line treatment, and the market demand is huge.
To expand market capacity, expanding the scope of indications is a shortcut. An insider of BMS revealed that the company was the first in China to complete the first PD-1/PD-L1 clinical study, which is unparalleled in scale. Gong Zhaolong said that although pharmaceutical companies are not allowed to market for hyperindications, patients may still be over-indications.
It is important to emphasize that patients with over-indication medications will be at their own risk. According to media reports, after Hong Kong martial arts star Ji Chunhua was diagnosed with advanced lung cancer, a large-scale top three hospital in Hangzhou was confirmed to have been unable to undergo surgery, chemotherapy, radiotherapy and other treatments. After learning about the illness, Hong Kong friends specially purchased PD-1 from Hong Kong. The immunotherapeutic drug (Kreida, commonly known as K drug) is for his use. However, the treatment of two courses, the effect is not good, unfortunately passed away in July this year. Ding Lihua, CEO of Zero Technology, told the health point that one of the deaths of Ji Chunhua may be the acute multiple organ failure caused by the drug. However, for second-line treatment, there is no medicine to save, patients and their families are willing to "dead horses to live horse doctors."
Hyperindication medications also bring more uncertainty to oncologists' clinical decisions. Ji Dongmei, deputy director of Department of Oncology, Fudan University Cancer Hospital, said in an interview with R&D guests that although some indications are already undergoing clinical research, such as soft tissue sarcoma, PD-1 monoclonal antibody treatment is used in these patients with hyperindications. At the same time, it is still necessary to be cautious and the treatment effect may be less than expected. Tumors, such as malignant melanoma and recurrent Hodgkin's lymphoma, which have proven to be more effective, are more likely to try PD-1 monoclonal antibody therapy.
Channel: DTP pharmacy into the main channel of the initial stage of listing
At 4 o'clock on the morning of August 29, the first batch of O medicine arrived in Sinopharm Henan Company. When a child was finished, the medicine was put on the shelves, and the first bill was completed at 7:57. At 8:33 in the morning, Zhengzhou Pharmacy received the drug. Henan's first prescription.
Similar scenes have occurred in Wuhan, Hefei and Changsha.
On the first day of the O-pharmaceutical market, the performance of the DTP pharmacy system attracted industry attention. This is the treatment that Iressa, Gleevec and other "precursor gods" do not have. Compared with public hospitals such as Shanghai Chest Hospital, DTP pharmacies not only achieved the first time distribution, but also allowed cross-city distribution within the region. Zhang Xiaodong, CEO of Magnesium Health, which provides services for many DTP pharmacies in China, expects that DTP pharmacies will increasingly become the mainstream channel for special drug sales. The DTP channel of a certain three-generation targeted drug in China accounts for 90% of the time. It is expected to be listed on O-drug. In the early days, the proportion of DTP channels will be higher.
Ding Lihua revealed that the efficiency of drug administration in public hospitals is affected by the proportion of drugs formulated by the medical administrative department (the proportion of drug revenues to the total income of hospitals - editor's note), and is also affected by the total amount of medical insurance formulated by the medical insurance administrative department. Once the proportion of medicines and the total amount of medical insurance are approached or exceeded, the motivation for public hospitals to purchase high-value drugs will be greatly reduced. Coupled with the implementation of the elimination of drug additions throughout the country, public hospitals do not make money on drugs and drugs. In contrast, DTP pharmacies are not subject to these rules, which has led to the emergence of a prescription outflow market – patients prescribing in public hospitals and purchasing medicines at DTP pharmacies (to take medicine at the store or to deliver medicines to the door).
As early as June 22, Bristol-Myers Squibb (BMS) signed a strategic cooperation agreement with Shanghai Pharmaceuticals around O-Pharma. Although the signing parties did not disclose the details of the agreement, according to the information provided by Shanghai Pharmaceutical Health, on the first day of the listing of Opharmaceuticals, Shanghai Pharmaceutical Holdings fully accelerated and successfully completed the nationwide initial sale and expedited distribution to all parts of the country. On August 28th, as the DTP brand of Shangpin Yunjian, which is owned by Shanghai Pharmaceutical Holdings, “Yi Pharmaceutical·Pharmacy” started the sale of O medicine in the country, and provided services such as drug consultation, drug delivery, health management, and patient education. Up to now, “Yi Pharmaceutical·Pharmacy” covers 6 DTP pharmacies in 6 cities including Shanghai, Hangzhou, Changzhou, Nantong, Wuxi and Xuzhou.
On the same day, on the afternoon of the 28th, the neighboring customers and wisdom pharmacy under Zero Technology were the only DTP pharmacies in Heilongjiang Province, and completed 5 patients' drug purchase services within 4 hours. According to the information provided by the company, patients can use the DTP pharmacy to use pharmacy services, such as the whole process of adverse reactions during drug use, consultation on all aspects of drug use, and application of patient management system with independent intellectual property rights. Drug patients were followed up by medication.
In November 2017, under the guidance of the National Population and Health Promotion Committee of the National Health and Family Planning Commission, the research report on “China Tumor Patient Service Upgrade” jointly issued by Caixin Health Point and the China Anti-Cancer Association Rehabilitation Association showed that patients with cancer were diagnosed and treated. In the link, 52% of the respondents communicated with the doctor in charge for less than 10 minutes each time, and 70% of the respondents never received an invitation to the disease lecture from the hospital. For most cancers, including breast cancer, treatment technology advancement has achieved "long survival," which means that the long-term management of "cancer chronic disease" patients in medical institutions has proliferated, and hospitals cannot fully meet the needs of post-hospital follow-up.
In order to meet the above-mentioned patient needs, in addition to the introduction of medical social workers to participate in health science, the introduction of pharmacists to provide reasonable medication counseling services, also requires high-level social medical institutions to provide, such as some high-end private hospitals, DTP pharmacies, to provide health education for patients. Services such as disease management, to make up for the gap in demand left by public hospitals.
The experts interviewed expect that O medicine as a prescription drug needs to be prescribed under the guidance of a doctor. If the state encourages the DTP pharmacy policy to fall, the sales of DTP channels will be greatly increased. Since O medicine is an injection, intravenous administration needs to be completed in a hospital, and it is necessary to monitor adverse reactions after administration. Relatively speaking, large-scale hospital medication is safer. With the accumulation of medication experience, small hospitals, clinics and even DTP pharmacies that meet the treatment conditions will appear, but it is unrealistic to release them in the short term. A market expert who asked not to be named also reminded that it will take a long time for China to achieve a true “medical separation”. Although the president of a public hospital knows that selling medicine does not make money, the purchase of medicine is still a big power in his own hands.
Due to well-known reasons, some public hospitals with unobstructed access to medicines and adequate supply of medicines may use the safety of medication as an excuse to ban the use of purchased medicines (including DTP pharmacies) in our hospital. To this end, Zhang Xiaodong said that Magnesium Health has set up an external cooperation network. If some patients who purchase O medicine through DTP pharmacy are refused to be consulted in public hospitals, they can go to Shanghai Jiahui International Hospital for immunotherapy. However, because foreign-funded hospitals do not include basic medical insurance, patients are required to pay higher medical service fees.
But Ding Lihua believes that public hospitals and DTP pharmacies are not completely competitive. The advantage of DTP pharmacy lies in its differentiated development from hospitals. For high-value special medicines such as O medicine, if there are many DTP pharmacies in the sales system, why should the hospital divert prescriptions to a DTP pharmacy? Ding Lihua said: First, we must look at the above-mentioned value-added services provided by pharmacies. Second, we must see whether the Internet hospital can clearly price the price, and provide doctors with out-of-hospital prescriptions to provide legal pharmacy service fee income. Third, look at the promotion effect of the drug market and sales department; It is to see if the patient can directly ask the doctor to prescribe the prescription for medicine. For example, the DTP pharmacy will give the patient the profit of the channel difference, and the patient can enjoy the promotion period reward in the DTP pharmacy.
This article is reproduced from：https://news.pharmacodia.com/news/html/info/info-detail.html?id=29646
