A case study on the substitution of domestic imatinib for imported imatinib

Source: emeda 2016-8-2 1 Research introduction this study demonstrates the substitutability of domestic innovative drugs for imported drugs from clinical application, pharmacoeconomics, market performance and other dimensions through comparative analysis between domestic innovative drugs or generic drugs and original research drugs, so as to promote the independent research and development, innovation and market access of Chinese drugs Put forward policy suggestions for the reform of relevant policies, so that China's innovative drugs can play a real role of substitution In terms of variety selection, two generic drugs and two domestic innovative drugs are selected to analyze the quality consistency, real world sales performance, market access cases and pharmacoeconomics of their imported or imported products with the same pharmacological effects, and analyze the substitutability of domestic drugs for imported drugs, as well as the health resources that can be saved by using domestic drugs Benefit of the domestic sick population The analysis drug in this report is imatinib, and the comparison product is the imported imatinib and the first domestic imatinib tablet (hereinafter referred to as "the first imatinib tablet") 2 Product overview and characteristics imatinib mesylate is a tyrosine kinase inhibitor, which has the characteristics of targeting and specificity It is used for the treatment of chronic myeloid leukemia (CML) patients in the acute stage, accelerated stage or after the failure of α - interferon treatment; patients with malignant gastrointestinal stromal tumor (GIST) who cannot be surgically removed or metastasized Imatinib is the first approved tyrosine kinase inhibitor of the first generation, known as "a major breakthrough" in recent years, and has become the first-line treatment drug for CML and the first choice drug for gastrointestinal stromal tumors Imatinib mesylate was developed by Novartis, Switzerland It was approved to be listed in the United States on May 1, 2001 Its trade name is Gleevec Its indications are patients with chronic myeloid leukemia (CML) in the acceleration stage, the acute stage and the chronic stage of interferon resistance In February 2002, the second indication of the drug, gist, was approved In April 2002, Novartis imatini was approved for import and listed in China 3 The price of the first imitation imatinib tablet is only one tenth of that of the imported drug Imatinib is the first-line drug for the treatment of chronic myeloid leukemia, but the price of the imported drug is expensive In 2013, imatinib mesylate, the first domestic product, was approved for marketing by CFDA, and obtained the first new drug imitation certificate, breaking the price monopoly situation of foreign enterprises Price comparison: at present, the price of imported drugs is 12000 / box, 0.1g * 60 tablets per box, with an average of 200 yuan / tablet Under the same dosage form and specification, the price of the first imitation imatinib tablet is 20.83 yuan / tablet That is to say, the price of the first imatinib imitated tablet is about one tenth of that of the imported drug when the curative effect is equivalent to that of the imported drug Table 1 Comparison between the price of the first imatinib imitation tablet and the price of the imported drug product dosage form specification price imported imatinib 0.1g * 60 Tablets 12000 yuan / box, 200 yuan / tablet first imatinib imitation tablet 0.1g * 60 Tablets 1250 yuan / box, 20.83 yuan / tablet Through overcoming technical barriers, the manufacturer of the first imitation imatinib tablet has broken through the patent protection of the original manufacturer for the crystal form of the drug, and developed a crystal form patent with independent intellectual property rights Through clinical trials, it has been proved that the pharmacokinetic parameters of the first imitation imatinib tablet and the imported drug are consistent, which is equivalent to the efficacy of the imported drug (the project is subject to the "major new drug creation" of the state) Major special support for science and Technology) A Comparison of bioequivalence: the first imatinib tablet was approved in CFDA in 6 categories According to the review and approval requirements of CFDA, it has the same bioequivalence as the original drug, which is a necessary condition for the market In 2012, the first manufacturer of imatinib mesylate tablets carried out "a single center, open, randomized, two cycle cross bioequivalence test of imatinib mesylate tablets in Chinese healthy male subjects" in TEDA International Cardiovascular Hospital The clinical research approval No.: 2012l01852, 2012l01873 The results showed that the trial product imatinib mesylate (first imitation of imatinib tablet) and the imported reference preparation were bioequivalent preparations, and the subjects were well tolerated during the test Fig 1 blood concentration time curve of imatinib mesylate test preparation and imported drug B the first multicenter clinical study of imatinib tablet in cml-cp, led by Professor Huang Xiaojun of Peking University People's Hospital, 12 A team of famous experts from famous blood research centers and hospitals has designed and carried out a multicenter, prospective, single arm and observational study to evaluate the early response and safety of imatinib in the initial treatment of newly diagnosed cml-cp patients, and to provide evidence-based medical evidence for clinical use of imatinib The results of multicenter clinical trials show that the first imatinib tablet has excellent therapeutic response, most of the patients have reached the optimal therapeutic response standard of ELN, which is basically consistent with the published results of imported drugs, and the type and proportion of adverse reactions are basically consistent with the reports of imported drugs The early clinical efficacy is similar to that of imported drugs, and the price is lower than that of imported drugs China is a developing country, and less than two fifths of Chinese CML patients can afford the cost of imported drugs Therefore, the first imitation of imatinib on the market is of great significance to society and individual patients C Imatinib preparation reform in 2001, the original research imatinib came into the market, the selected dosage form is capsule In 2003, the original research company launched imatinib tablet due to the gastrointestinal tolerance of many patients Up to 2006, imatinib capsules were withdrawn from the market in most countries At present, imatinib tablets are the most frequently prescribed dosage forms Compared with the capsule shell, the excipient composition of the tablet is more simple, and the patient's digestive tract tolerance is better under the condition of super long-term use At the same time, all production links of tablets are in GMP environment, while capsule shell needs external procurement Therefore, the production quality of tablets is more guaranteed In addition, imatinib has a variety of crystal forms, among which the common α crystal form is needle like and the crystal form is relatively coarse, so it is difficult to produce qualified tablets, while the patent of β crystal form suitable for tablet production will not expire until 2018 For this reason, the first manufacturer of imatinib imitated imatinib tablets invested additional research and development costs, developed patented crystallization technology, and successfully produced a non acicular α crystalline imatinib Like the original β crystalline imatinib, it can produce stable and qualified tablets, while maintaining the same excipient composition as the original imatinib tablets 5 The real world sales performance of the first imitation imatinib tablets and imported drugs a the growth rate of imatinib's national sales volume is significantly higher than that of the amount IMS data shows that in 2014, the amount of imatinib used in the National Hospital was 878.67 million yuan, and the national sales volume in the first three quarters of 2015 reached 92, 8.32 million yuan, with a three-year average growth rate of 39.31%; in 2014, the number of imatinib drugs used in hospitals across the country was 5.87 million pieces, with a national sales volume of 8.51 million pieces in the first three quarters of 2015, with a three-year average growth rate of 59.13%; the growth rate of quantity was significantly higher than that of amount B Less than 50% of imported medicinal products account for more than 90% of the market share of imatinib in China With the development of imitation imatinib in China, the market share of imported drugs is declining year by year; however, the decline speed of the market share of the amount of imported drugs is far lower than the decline speed of the market share of the quantity; the amount share of the first imitation imatinib tablets and other generic drugs has been close to the imported drugs, but the amount share of imported drugs still accounts for more than 90% of the imatinib market in China; the import medicine is less than 50% The quantity share of imatini accounts for more than 90% of the amount share of imatini market in China, and its high price is self-evident Figure 3 drug amount of imatinib production enterprises in national hospitals from 2012 to 2014 Figure 4 drug amount of imatinib production enterprises in national hospitals from 2012 to 2014 table 6 drug amount and quantity share of imatinib production enterprises in national hospitals from 2012 to 2015q3 Commodity name 2012 2013 2014 2015q1-q3 amount share quantity share quantity share quantity share quantity share Amount share quantity share import medicine 100% 100% 99.58% 97.70% 95.85% 72.95% 90.11% 49.98% first imitation imatinib 0% 0% 0.33% 1.74%, 3.36%, 21.67%, 7.75%, 39.06% other domestic imatinib 0.00%, 0.00%, 0.09%, 0.55%, 0.79%, 5.38%, 2.14%, 10.96% totally 100.00% 100.00%, 100.00%, 100.00%, 100.00%, 100.00%, 100.00%, 100.00% C market access cases of the first imatinib imitation: provincial medical insurance access policies have become the main factor limiting the development of the first imatinib imitation 2015 In the first three quarters of this year, according to the analysis of imatinib in China's provinces, the proportion of imported drugs is relatively large in several provinces The medical insurance policies of most provinces have formed various restrictions on the first imatinib tablet The medical insurance access policies of each province have become the main factors restricting the development of the first imatinib tablet Hebei Province: medical insurance for urban residents only includes imported drugs in the payment scope of medical insurance; Zhejiang Province: medical insurance for serious illness only includes imported drugs in the payment scope of medical insurance; Guangdong Province: medical insurance has not implemented the first reimbursement policy of imatinib tablet as of February 2016; Yunnan Province: New rural cooperative medical insurance only includes imported drugs in the payment scope of medical insurance; Xinjiang: imported drugs are only included in the payment scope of medical insurance for serious illness It can be seen that adjusting the reimbursement policy of medical insurance, implementing the reimbursement amount of imatinib according to the domestic generic drugs with the same quality level, and rapidly increasing the market share of excellent domestic generic drugs can save more social security funds and benefit more patients Table 8 sales volume share of imatinib in some provinces in 2015 q1-q3