文 | 袁勇 续梦婷
In 2014, a rare disease to help patients with amyotrophic lateral sclerosis (also known as amyotrophic lateral sclerosis) of the ice bucket challenge activities worldwide popular, so many people understand the concept of rare disease. Because of the small number of patients with a single disease, rare disease patients are also known as orphan drugs. How can such a small number of people can enjoy the social welfare and care? In December 21, 2016, the State Council executive meeting to determine the 13th Five-Year during the key tasks of deepening medical reform, proposed to improve the system to ensure the supply of drugs, cheap drugs, support the orphan drug, children’s drug production.
The source of | Economic Daily
This paper | Yuan Yongxu Meng Ting
At present, China’s rare disease patients with drug supply security problems? What are the causes of these problems? What are the possible ways to improve? With these questions, the reporter visited the patients, experts, pharmaceutical companies and relevant departments.
International rare disease day, the rare disease center of public interest organizations launched a rare disease family documentary photography exhibition, the introduction of rare disease groups living conditions. Liu Yun photo
A smile is now a full-time staff of a mucopolysaccharidosis patient tissue, usually in line with the patients and their families to share medical information etc.. Island.
1 of a new orphan drug to Chinese made
Recently, the reporter saw Zhang Xiao mucopolysaccharidosis type I patients in Beijing. Mucopolysaccharidosis is a rare genetic disease in patients with recessive body presentation body stiffness, corneal opacity, hepatosplenomegaly, airway obstruction and other symptoms. Illness has brought great pain and inconvenience to Zhang smile, I can not even wash their own hair, wearing socks. At the same time, Zhang also faces a helpless reality: the domestic long-term situation in patients with sticky polysaccharide drug free. At present, there is no effective drugs for this disease, by the United States Malin company Aldurazyme is a specific drug for the disease I. The drug was listed in 2003, but was not introduced into the country.
Zhang laugh situation similar to patients with many. The reporter visited many patients and experts found that many domestic rare disease is completely dependent on imports of drugs, if the drug is not in the domestic market, will face no drug use situation, innovative orphan drug invisible China made.
In the view of president of Shandong province Han Jinxiang rare disease prevention association, to enhance the capability of research and development of domestic pharmaceutical companies orphan drug, to produce the Chinese orphan drug, is the fundamental way to solve the domestic rare disease medication dilemma. However, compared with developed countries, China’s orphan drug R & D capability is lagging behind, innovative orphan drug output is almost blank. Capital Institute of Pediatrics Professor Song Fang told reporters: in the current new drug in the world, orphan drugs have accounted for about half the proportion of ‘orphan drugs’ research ability has become an important embodiment of research and innovation capacity in the field of medicine. In this respect, our country is in a very awkward position.
What are the reasons for this gap? A rare disease development center director of the nonprofit organization Huang Rufang believes that the domestic pharmaceutical companies orphan drug research and development is weak, largely because of the lack of incentive mechanism. In Europe and the United States, there are different types of incentives to promote orphan drug research and development.
Relevant research documents show that in 1983, the United States orphan drug development is equally difficult. Turning point is the United States in 1983 released the orphan drug act. 2002, the United States, the rare disease act was introduced, so that rare disease research has a clear legal protection, rare disease research fund has gradually increased, making the United States orphan drug development and protection system is more perfect. At present, the development of the pharmaceutical companies in the whole process of orphan drug enjoy clinical research grant funds support and tax credit policy, at the same time, the drug can be given after the listing, the enterprise 7 years of market exclusivity. Since the orphan drug act was enacted, the number of applications for orphan drugs in the United States has increased significantly. From 1972 to 1982, only 10 orphan drugs listed, from 1983 to 2015, there are nearly 500 orphan drugs on the market, with annual sales of more than $40 billion. At the same time, the United States orphan drug policy has attracted a number of countries and regions in the world to follow suit.
In contrast, the current our country for rare disease problems of special legislation is still blank, orphan drug policy related only in drug safety supervision system etc.. A number of pharmaceutical companies told reporters that the pharmaceutical R & D relevant incentive policies at the national level unified innovation in the aspects of medicine, pharmaceutical companies to obtain relevant incentives, orphan drug only with other innovative drugs blanketly into innovative drug related incentive policies for channel. The two drugs listed cost almost the same, the incentive mechanism is no difference, but the market demand continues to be quite different, pharmaceutical companies to conventional drug development focus on the greater market demand will be not at all surprising.
National People’s Congress Sun Zhaoqi since 2006 to adhere to the proposal and the proposal of a rare disease related. In his view, to change the domestic orphan drug research weakness of the situation, it must be through special legislation to tilt policy, to speed up the rare disease specific legislation, is to solve the most urgent need to lag the current plight of rare diseases and ‘orphan drugs’ research and development. Favorable policies to promote market forces to solve the orphan drug research and development and output problems, but also many experts and scholars of the common view.
At present, the global orphan drug market is in a rapid growth stage, however, the lag is R & d let our pharmaceutical companies miss in the huge orphan drug market gets more profit opportunities. The pharmaceutical market research firm Evaluate Pharma released the 2015 orphan drug market report shows that the current global orphan drug market with the annual growth rate of nearly 12%, compared to the first half of 2015, the global average market growth rate of only 5.9%. The report predicts that by 2020, the global orphan drug sales will reach $178 billion, orphan drugs in all prescription drug sales accounted for more than 20% of the total is expected to exceed. The world’s major pharmaceutical giants are also targeting this market, mergers and acquisitions and other ways to expand their share of the orphan drug market. At the same time, China’s domestic pharmaceutical companies to produce the orphan drug has almost all generics, huge profits and innovation gap, resulting in China’s pharmaceutical companies to share the high profits in the orphan drug market, innovation ability and market value are greatly restricted.
2 high priced orphan drugs can enter Medicare
For pharmaceutical companies, research and development of innovative drugs often require huge investment. The orphan drug market demand is very small, the pharmaceutical companies to want to cover costs of listing by R & D and sales profit, and get good returns, often use the patent protection of drugs price will be very high.
The mucopolysaccharide drug Aldurazyme as an example, according to the market price, the annual cost of each drug in patients with at least 2 million yuan, which makes the patient look medicine helplessly. Zhang Xiao told reporters, even if there is a way to buy drugs from abroad, or simply can not afford to buy, the price is too expensive, so I can only do regular check, the body which organ problems, do some local treatment. Zhang Xiao said that she was able to contact the domestic patients have more than and 300 people, the basic treatment and she is similar.
Malin, China’s market access manager, said Cao Wen, if the drug can not enter the health insurance directory, it is difficult for patients to use drugs. At present in the domestic promotion of ‘orphan drugs’ cost is not small, including clinical trials and the registration and approval of investment, health insurance negotiation, patient donated medicine etc. at the same time, the high price of Aldurazyme, almost impossible by patients at their own expense medication, must be obtained in the Medicare payment market, currently still does not have such conditions. Cao Wen said, Aldurazyme in a number of countries and regions, are included in the directory of health insurance, to reduce the economic burden of patients to obtain the market. Cao Wen also said that in view of the Aldurazyme in the domestic market is approved, the relevant departments of pharmaceutical companies and a number of local governments had to communicate, but there is no progress, all departments are said to be in after obtaining the qualification to consider whether the drug into the health insurance directory.
In our country, as a result of rare disease drugs generally do not belong to the basic drugs, whether or not the right to be included in the health care sector in the relevant departments. But for the place, the decision whether the drug into the medical insurance must be registered after the relevant calculation, therefore, in accordance with the existing provisions of the relevant departments of the practice of understandable.
To promote more orphan drugs into the health insurance directory, how much pressure? Ministry of human resources and social security data show that the basic medical insurance fund in 2015 the annual total income of 11193 towns in China billion yuan, spending 931 billion 200 million yuan, the urban basic medical fund accumulated balance of 811 billion 400 million yuan, higher than the revenue expenditure, the balance of the number of about 10 months the average level of payment. In 2009 the Ministry of human resources and the Ministry of Finance issued on the further strengthening of the basic medical insurance fund management guidance and pointed out that the urban workers basic medical insurance pool fund accumulated balance principle should be controlled in 6 to 9 months on average pay level. The current balance is slightly higher than the scope of the principle, showing that China’s current medical insurance fund has a strong ability to pay.
However, there are many voices of concern. Han Jinxiang believes that due to Chinese rare disease type and the number of people who, high import orphan drug price, if the mass into health care, is likely to gradually affect other common diseases, the patient’s medical payment, the fact that this situation has emerged in europe. At the same time, some experts believe that the balance of higher medical insurance fund to cover up the difference exists in the whole area, in some areas, the balance has even reached the average level of payment for more than 20 months, but at the same time, many regions have to make ends meet, the situation is quite different from.
Shi Luwen, director of pharmacy administration and clinical pharmacy department of Peking University School of Medicine said that due to differences across the country are medical overall level and financial income level, if the country can introduce a macro policy, according to local area incidence and level of economic development and its situation of construction assistance system, is the more appropriate assistance system.
In fact, some areas of the country’s high level of economic development has begun to gradually explore more rare diseases into the health care system. In 2016, a rare disease in Zhejiang province will include Gaucher disease, amyotrophic lateral sclerosis, phenylketonuria, into the medical security system. Amyotrophic lateral sclerosis and phenylketonuria treatment costs each year for more than ten million, Cerezyme treatment of Gaucher disease in the domestic purchasing costs need each with at least 2 million yuan a year, and need lifelong medication, these diseases were included in the health care system, greatly reducing the financial burden of patients. It is reported that the rare disease patients are included in the scope of protection, will be the basic health insurance, serious illness insurance, medical assistance, financial special funds, such as the level of sharing to resolve its compliance medical expenses.
But in most areas, compared to the needs of patients, the rescue system is slow, difficult to use, expensive medication is very prominent. In 2016 NPC and CPPCC, Sun Zhaoqi suggested that the protection of rare disease medical system in the country to promote the Zhejiang Province, in order to reduce the burden of patients, many patients and their family poverty caused by illness, become an indispensable part of our country especially poor population.
At the same time, some experts believe that if the price of orphan drug can be further incorporated into the local health insurance directory, reduce the burden of patients, can obtain the bigger market for orphan drug research and development of domestic pharmaceutical companies, is also a huge incentive.
3 listing looks green channel
In accordance with the provisions of the patent protection period after the expiration of the new drug, pharmaceutical production of generic drugs, but the need for consistency evaluation process, qualified rear can be listed. Generic drugs are often much cheaper than innovative drugs and become an alternative for many patients. However, the reporter found that, for many rare disease patients, the use of imitation orphan drug is also facing difficulties. This is because the cost of listed drugs did not differ with other conventional drugs and generic drugs also lower price lead to lower profits, to cover costs of listing, the enterprise will promote the inhibition of drug.
Momoco is a rare disease in children with congenital adrenal hyperplasia of the mother, for a long time, she has been plagued by twists and turns to buy medicine. Hydrocortisone is essential drugs, the treatment of congenital adrenal hyperplasia in China, Shanghai Xinyi Medicine Pharmaceutical Company Limited also the production of alternative medicine, but only the 20 mg dose of the product. Momoco said: this disease for the drug dose accuracy requirements are high, give children medication is generally 5 mg dose, 20 mg of drugs only to adults, if the medication is not accurate, will cause a lot of side effects. The appropriate dose of drugs can only be purchased abroad. Momoco said that she had to communicate, and other foreign pharmaceutical companies said, because the drug profits is too low, can not cover the costs of listing, so do not want to enter the market Chinese. She can only buy drugs from abroad, which brings a lot of policy risk to Momoco.
In this regard, the reporter contacted the drug Xinyi pharmaceutical factory. The drug Xinyi said that if the permit production company acquired 5 mg or 10 mg of specifications for Hydrocortisone Acetate Tablets, and the market demand, the company will timely organize production, meet the clinical needs of patients. However, to obtain production approval, drug development and approval cycle is longer, the cost is large, if the market is very small, the enterprise must consider the management burden problem.
The same dilemma is also reflected in the new use of old drugs. Tao Zi is a rare disease in patients with tuberous sclerosis, taking drugs mainly for generic pharmaceutical sirolimus. Despite the obvious curative effect, but does not contain the specified sirolimus indications of tuberous sclerosis, in this case, patients are required by the doctor application item. In addition, some hospitals in Beijing, Shenzhen and other places in the clinic by medicine ethics Association for the record, can also prescribe medication, but the patient is in the reagent status rather than the identity of patients with medication, to sign an agreement with the risk of doctors, which makes the patient’s medication process is very complicated.
We want to be able to promote the use of new drugs’, so that more patients can use this medicine, because it is cheap, patients can afford. Tao Zi told reporters that although there are 4 domestic pharmaceutical companies in the production of sirolimus, but only the North China Pharmaceutical expressed willingness to cooperate, the rest of the negative attitude of pharmaceutical companies, so the North China Pharmaceutical is also a great concern, because if they spent a lot of cost push drugs to increase the indications, other companies also benefit, while other companies have entered the many hospitals, higher market share.
One obstacle is the lack of incentives, the other side is related to high cost. North China Pharmaceutical official Jiao Jinping said, according to the current policy, to new indications, it normally takes about 3 years of processing time, companies need the burden of drug costs, treatment costs, and funds from the time of speaking, it takes a lot of cost calculate accounts, other companies will not have too many enthusiasm.
In accordance with the relevant provisions of the new drug clinical trials often need to get enough cases to support. Due to a rare disease often lack sufficient cases, in rare disease drugs before entering the market, the pharmaceutical companies will submit the clinical trial exemption or reduced sample size applications, but need each drug separately submit registration. Sanofi communication departments may Jiaying said that the current approval will greatly increase the industry cost of time, I hope the relevant departments issued clear regulations, with clear principles of rare disease drug can get free clinic, or directly from abroad data, and priority review, and do not need to apply separately for each.
In fact, to promote the orphan drug market, the State Food and Drug Administration issued a series of new drug approval documents of the reform, proposed a rare disease and other special groups to give up drug review, priority review, but the effect is not obvious. Huang believes that first of all, because of the lack of rules of these policies, the implementation of the relevant departments is not clear. In addition, China’s rare disease drugs and conventional drugs in the same approval channels, the lack of a separate examination and approval path, there is no way to improve the efficiency of examination and approval.
In the text, Momoco and Tao Zi are aliases
4 work started on the road
On this issue, the first step in Shanghai. 2016 in February, Shanghai issued a list of major rare diseases in Shanghai (version), the 56 diseases were included. National authorities have begun to pay attention to this problem, in December 2015, the national health and Family Planning Commission set up a rare disease diagnosis and protection of the expert committee. The State Planning Commission, told reporters, at present, Wei Planning Commission relies on the Committee of experts has carried out the following work: one is the selection of the first batch of rare disease directory to start, according to technical methods, a diagnosis of drug cure or significantly relieve symptoms and control society reflects the more prominent principle, make the first selection of rare disease standards and procedures, and start the selection work; two is the rare disease drug security review and investigation, the Committee of experts has been combing the rare disease drug security situation in China, began investigating the status quo of China’s rare disease diagnosis and treatment, research and drafting of regulations of our country in order to improve the diagnosis and treatment of rare diseases, and the level of protection is put forward opinions and suggestions. Next expert committee will be based on the responsibility to study the definition of rare diseases and disease.
At the same time, some experts believe that to speed up the orphan drug review and approval, have very detailed data base support, to ensure the safety and effectiveness of drugs, this is China’s orphan drug research and development of the short board, at present, China’s serious distortion of epidemiological data and weak research. Therefore, experts continue to advocate and promote the registration system for rare disease patients to help establish a rare disease database. The database can complement the lack of epidemiological data, improve the scientific basis and core knowledge of orphan drugs, can also provide quantitative data to support drug development, the pharmaceutical companies in drug design is more reasonable. Huang Huang said.
Inspired by this, many domestic rare disease organizations began to collect all kinds of rare disease related data, including the distribution and treatment information of rare diseases, orphan drug research and development, production and sales information, and orphan drug dosage, clinical use of information, in order to effectively promote the future orphan drug clinical trials . Shandong Province rare disease prevention association provincial rare disease organizations are organized based on a nationwide investigation of rare diseases, and obtained the national science and technology support program funding.
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