There are three advantages for the use of rare disease drugs. Will generic drugs for orphan drugs break the ice first?

Rare diseases refer to the diseases with low prevalence and rarity There are different definitions of rare diseases in the world The World Health Organization defines rare diseases as diseases or pathological changes that account for 0.65 ‰ to 1 ‰ of the total population The definition of rare diseases in China proposed by the Chinese Medical Association Medical Genetics branch is the disease with a prevalence of less than 1/500000 or a neonatal incidence rate below 1/10000 Due to the small number of patients, low market demand and high cost of research and development, few pharmaceutical companies pay attention to the research and development of rare disease treatment drugs, so these drugs are vividly called "orphan drugs" With the support of FDA and other registration laws and regulations, foreign pharmaceutical companies actively develop orphan drugs From the perspective of rare disease drugs that have been listed in China, the original manufacturers of drugs listed are mainly imported pharmaceutical enterprises There are few rare diseases in which the research and development of new drugs are located outside of tumors in domestic enterprises On May 11, 2017, CFDA's announcement on Soliciting Opinions on relevant policies on encouraging innovation of medical devices and accelerating the review and approval of new medical devices on the market (Draft for comments) (No 52, 2017) once again reiterated the state of CFDA's support for research and development of rare disease treatment drugs Does this mean that drugs for rare diseases will break the ice? There are three main policies for the use of drugs for rare diseases and orphans in No.52 document of breaking ice signs for the use of drugs for rare diseases: 01 the list of rare diseases will be published soon, and the health and family planning department will publish and establish a registration system for patients with rare diseases This means that the epidemiological data of rare diseases are expected to be established, and the problem that patients cannot be found in the clinical research and development of drugs related to rare diseases is expected to be solved with the establishment of the registration system for patients with rare diseases In 2016, Shanghai released the list of major rare diseases in Shanghai (2016 Edition) of 56 diseases Among them, there are 33 kinds of endocrine and metabolic diseases, 8 kinds of blood diseases, 7 kinds of immune diseases, 3 kinds of bone diseases, 1 kind of skin diseases, 1 kind of kidney diseases, 1 kind of facial features diseases, 1 kind of digestive diseases and 1 kind of cardiovascular diseases (see table 1) Table 1 list of major rare diseases in Shanghai (2016 Edition) 02 applicants for drugs for treatment of rare diseases in priority review can apply for reduction or exemption of clinical trials to speed up the review and approval of drugs for rare diseases In fact, in 2016, the opinions of the General Administration of the people's Republic of China on solving the backlog of drug registration applications and implementing priority review and approval (sfjyhg [2016] No 19), it was also mentioned that drug registration applications with obvious clinical advantages to prevent and treat rare diseases will receive priority review and approval Since 2016, a total of 15 acceptance numbers have been included in the list of priority review and approval, and all of them have been included in the list of priority review varieties Recombinant human clotting factor Ⅷ is the product with the largest number of manufacturers' declaration and acceptance It can be seen from table 2 that there is no priority review and approval for new drugs of rare disease chemicals independently developed in China Table 2 priority review and approval list of orphan drugs (data source: Xianda data v3.2) 03 exempt from clinical review For rare disease treatment drugs approved to be listed in foreign countries, they can be approved to be listed conditionally, and relevant research shall be conducted within the specified time after listing In fact, there have been cases in the clinical practice of drug immunity for rare diseases The indications of sunitinib malate capsule approved in 2010 are to produce anti-tumor and anti angiogenic effects by inhibiting multiple targets In 2012, when the wholesale disease incidence rate was about 0.3/10 million for the rare disease of acetonicendocrine neoplasm, the global clinical trial data were comprehensively reviewed, and the strategy of exemption from clinical trials was approved to approve the listing In 2012, the products that were exempted from clinical trials and approved for marketing were not only rare disease drugs but also children's drugs, that is, the only internationally approved drug for treating premature infants with apnea, caffeine citrate injection In 2016, Chengdu Yuandong Pharmaceutical Co., Ltd., as the first domestic imitation application for caffeine citrate injection, also obtained the priority review and approval, and was approved in 2016 In conclusion, rare disease drugs and children's drugs can be exempted from clinical cases for a long time If this measure becomes a policy, domestic enterprises will actively introduce rare disease generic drugs into China In the review of approval, it is not every year that orphan drugs are approved In the drug review report issued by CDE in 2010, it is mentioned that primary pulmonary hypertension is a rare disease 　　 In 2010, the company approved the import and marketing of cetastatin sodium; approved the entry of soluble guanosine cyclase (SGC) agonists and long-acting non prostaglandin prostaglandin receptor (IP receptor) agonists into clinical trials; approved imatinib mesylate tablets for the treatment of dermatofibrosarcoma protuberans (DFSP) with conditions; approved new compounds for the treatment of idiopathic pulmonary fibrosis Heart clinical trial In the 2012 annual drug review report, it was mentioned that two drugs for rare diseases were approved, one was desetabine for injection for the treatment of myelodysplastic syndrome (MDS), the other was sunitinib malate capsule for increasing the indication of acetylneuroendocrine tumor, a rare disease In the 2013 drug review report, troprostil injection mentioned is a drug for the treatment of pulmonary hypertension In the 2015 drug review report, it was mentioned that glucosidase α for injection was the only orphan drug approved for Pompeii disease in the world It can be seen from the drug review report published by CDE that drugs for rare diseases are not approved every year, and idiopathic pulmonary hypertension is the most approved indication In view of the fact that malignant tumors also belong to the scope of indications for priority review and approval, the relevant indications will not go through the green channel of rare diseases It is difficult to enter the medical insurance situation The manufacturer's motivation for price reduction is insufficient There are many orphan drugs in the medical insurance catalog in 2017, such as pirfenidone, another immunosuppressant limited to specific pulmonary fibrosis In 2016, enhuacoruzole, which entered the payment scope of special drugs and medical assistance (special assistance) scope of Zhejiang serious illness insurance to treat amyotrophic lateral sclerosis, as well as desetabin and recombinant human coagulation factor Ⅷ for injection mentioned above Imatinib entered the 2017 medical insurance catalog, but the above rare disease indications (dermatofibrosarcoma protuberans) are not covered by the reimbursement Bosentan tablet for the treatment of pulmonary hypertension has also entered 44 Medical Insurance negotiation drug catalogues published by the Ministry of human resources and social security in April 2017 The product has previously entered the special drug catalogues of serious illness insurance in Shandong, Shenyang, Shenzhen and other provinces However, there are some news that bosentan tablet failed to enter the medical insurance in the negotiation Generally speaking, orphan drugs are mainly reimbursed by entering the list of special drugs for serious illness insurance in various provinces and cities through negotiation, which means that manufacturers need to negotiate with people's and social sectors in various provinces and cities to enter the list of medical insurance Orphan drugs are never short of clinical needs In terms of manufacturers, the price of orphan drugs entering the medical insurance is lower than that of the number of patients increasing In contrast, the product price is not reduced, and the market scale obtained by manufacturers is larger The entry of rare diseases into medical insurance shows more humanistic care In summary, the current financial incentives are mainly universal high-tech industry incentives and the transformation of scientific and technological achievements There is no exclusive favorable policy for orphan drug research and development or production tax exemption, and domestic enterprises lack the motivation to research and develop new orphan drugs In terms of drug accessibility, the current incentive policy for orphan drugs should start from ensuring drug supply For example, domestic enterprises should introduce orphan drug generic drugs that have been listed in the international market and have proven clinical efficacy Even if the original research drug is not listed in China, can orphan drug generic drugs be exempted from clinical practice?