Talk about tenofovir again! Pay homage to the medical practitioners who witnessed the changes of the industry

With the approval of Chengdu Beite, guangshengtang and Qilu pharmaceutical tenofovir one after another, the controversy of tenofovir's first model has finally come to an end Shopping malls are like battlefields Behind the listing of each product is an invisible smoke What are the hard games behind the listing of tenofovir? Xiaobian is here today for a brief review to pay tribute to the pharmaceutical practitioners who have written this history and witnessed the changes of the industry Why is tenofovir on fire? China is recognized as a big country of hepatitis B, with 93 million hepatitis B carriers and 22 million hepatitis B patients According to the annual treatment cost of 5000 yuan and the penetration rate of 10%, the annual treatment cost of hepatitis B patients is about 11 billion In 2016, the sales volume of single product of Zhengda Tianqing Runzhong (entecavir dispersible tablets) was HK $3.5 billion, which shows that the market potential of hepatitis B in China is extraordinary At present, there is no complete cure for chronic hepatitis B, the main antiviral drugs are interferon α for injection, pegylated interferon α, and oral nucleoside drugs lamivudine, telbivudine, adefovir dipivoxil, entecavir and tenofovir dipivoxil Among these drugs: interferon drugs are inconvenient for administration, obvious adverse reactions and limited market promotion space; lamivudine resistance is increasingly prominent; adefovir dipivoxil resistance rate is low, but the antiviral effect is weak, which is commonly used in lamivudine resistant patients; telbivudine has no obvious advantage in drug resistance and antiviral effect, and has been tepid The oral antiviral drugs entecavir and tenofovir dipivoxil are recommended as the first-line and long-term treatment drugs for hepatitis B by the global guidelines because of their advantages of convenient administration, strong efficacy and low drug resistance Compared with entecavir, tenofovir is less resistant, and has no cross resistant sites with lamivudine and telbivudine, and can be used in pregnant patients It has become a battleground in the domestic hepatitis B market However, tenofovir has certain renal toxicity Gilead listed TAF again in 2016 TAF has high blood stability When the dose is less than one tenth (25mg / 300mg) of tenofovir, it can play a similar effect with the latter and improve the safety (see: good news! Vemlidy (TAF), the best new hepatitis B drug in history, was approved for marketing At present, TAF has not been listed in China, and Zhengda Tianqing has applied for the improved products of TAF (see the road of improvement and innovation of Zhengda Tianqing from the first new drug of 2.1 category "aiphenfovir") TAF may become the next hot spot in the hepatitis B market 02 The mystery behind the application and registration of tenofovir has been introduced for many times Tenofovir entered China in 2008 as an AIDS patient and was approved for hepatitis B indications on August 1, 2013 The earliest application time of TDF of Zhengda Tianqing, Chengdu Beite, guangshengtang, Qilu pharmaceutical and other enterprises was between 2008 and 2014, so there were different registration classifications In some provinces, only 6 kinds of drugs (AIDS) can be applied for 3.4 types of hepatitis B indications, and one acceptance number can carry both AIDS and hepatitis B indications (Chengdu Beite belongs to this situation) Some provincial bureaus allow separate declaration of category 3.4 Guangshengtang declared hepatitis B indications according to the original registration classification of 3.1 and HIV indications according to the original registration classification of 5 To some extent, the registration classification determines the time of listing of tenofovir from different manufacturers The main declaration manufacturers of tenofovir The figure above reviews the main players and their declaration process in the domestic tenofovir listing competition In hindsight, the most unsatisfactory performance is liver disease leading Zhengda Tianqing is the first to declare in Category 6 or 3.4 However, both categories 3.4 and 6 have been withdrawn At present, only one category 4 application is under review Chengdu Beite is the most successful one to be listed Although the registration classification shows that it is 3.4, it has finally completed the registration by only relying on be, and it is the first to be listed with AIDS indication through AIDS priority review policy, and then to increase hepatitis B indication through supplementary application, which can be described as Shunfeng Shunshui (see: the first doubt about listing of tenofovir) Guangshengtang, as a class 3.1 new drug, has completed a randomized, double-blind, large-scale clinical trial of 320 patients The clinical research lasted for 5 years, with an investment of more than 50 million yuan Of course, it also includes winning the patent lawsuit with the original manufacturer Gilead, paving the way for the listing of all domestic tenofovir (see: tenofovir hepatitis B first imitates the market! For the benefit of Chinese patients), it is not easy for guangshengtang's tenofovir to win the first identity of hepatitis B The luckiest one is Qilu Although the application time is later than Zhengda Tianqing and Anhui Baker, with the successive failure of the two companies, Qilu's six categories of generic drugs succeed Interestingly, in fact, Qilu's six categories of generic listing applications (September 30, 2013) are earlier than Chengdu Beite's 3.4 categories (August 5, 2014) and guangshengtang's 3.1 categories (July 23, 2014) 03 who is the first copy of hepatitis B? In November 2016, Chengdu betenovir dipivoxil tablets were approved for listing, becoming the first manufacturer of TDF in China However, this first imitation only approved HIV infection (AIDS), excluding hepatitis B indications Who will become the first manufacturer of tenofovir hepatitis B indications to become the focus of attention On May 23, the circle of friends almost simultaneously appeared the production approval documents of guangshengtang listing for tenofovir and Chengdu Beite supplementary application for hepatitis B indications approved At this time, there was also the news that qiluitenofovir was approved for listing So who is the first copy of hepatitis B indications? It can be seen from the CFDA query results that the completion time of the certificate preparation for guangshengtang class 3.1 declaration acceptance number is 14:06:35 on May 23, the completion time for Chengdu Beite supplementary application is 14:07:34 on May 23, and the completion time for Qilu class 6 declaration is 13:46:37 on May 23 Although Qilu finished the preparation of the syndrome relatively early, it is understood that Qilu's approved adaptation is not hepatitis B, that is to say, guangshengtang won Chengdu Beite by a minute, becoming the first manufacturer to imitate tenofovir's hepatitis B indications Now it seems that it is not important who is the first imitator of hepatitis B the products of follow-up enterprises such as Zhengda Tianqing and Anhui Baker are not far from being listed The market division of tenofovir depends more on the overall strength of the company Once again, to clarify the problem of first imitation is mainly to explain the complexity behind drug registration 04 is the tenofovir of GST a category 3.1 or a category 5? Gilead guangshengtang tenofovir was originally developed as a tablet After the dosage form was changed, guangshengtang tenofovir capsule was declared in accordance with 3.1 (hepatitis B indication) and 5 (AIDS indication), among which 5 types of production application acceptance No cxhs1300370 was withdrawn on December 15, 2015 According to the approval announcement issued by guangshengtang on May 24, the acceptance number of tenofovir fumarate is cxhs1400157, and the registration classification shows that it is the fifth category of original chemicals According to the information of CDE, the registration classification of cxhs1400157 is class 3.1, and guangshengtang has also made great clinical application according to the requirements of class 3.1 There are different registration categories for the same acceptance number in the announcement and CDE of guangshengtang The reason is not clear 05 Domestic tenofovir is listed for the benefit of Chinese patients After the enterprises represented by guangshengtang won the patent lawsuit against Gilead, the listing of domestic tenofovir has become barrier free GSK During the price negotiation with the state, we had to reduce the price by a large margin The average monthly drug cost of Werder, the original drug for tenofovir, dropped by 67%, from 1500 yuan to 490 yuan, becoming an affordable civilian drug for ordinary Chinese hepatitis B patients However, the price space left by the original products for domestic tenofovir is not large According to the latest bid winning price of Chongqing, the bid price of Chengdu Beite tenofovir is 456 yuan / box (0.3g * 30) Compared with the original research, it is only 7% cheaper How other manufacturers price their generic products for novovir remains to be seen Although the complicated drug registration situation of tenofovir is a "smart fight" conducted by different manufacturers around their own interests under the premise of complying with drug registration laws and regulations, we should still see the efforts made by domestic enterprises to break the original research monopoly, see the courage of national drug regulatory agencies to change and improve regulatory policies, and ultimately benefit the most Or the patient.