The future domestic market of hepatitis C DAA: who is in charge of ups and downs?

◆ hepatitis C market in China: the virgin land to be developed started this year, FDA approved the combination or non combination of elbasvir / grazoprevir, a double compound of Merck hepatitis C, for the treatment of hepatitis C patients with genotype 1 and genotype 4 As soon as the news came out, the drug market of hepatitis C DAA (direct antiviral) in the United States became more and more lively: harvoni of Gilead's family, viekira Pak of abbvie's family and the compound of Merck's family, the drug market of hepatitis C in the United States may be a little crowded In China, since the first generation of nsc3 / 4A inhibitor boceprevir was approved by the United States in 2011, there has not been an oral drug for hepatitis C on the market The treatment of hepatitis C is still the traditional interferon plus ribavirin However, China's hepatitis C drug market is so large that any company that does liver disease drugs cannot ignore it The R & D of hepatitis C has come to an end in foreign countries, but it is the "Warring States" era in China Foreign enterprises have not yet taken the lead Domestic enterprises catch up with each other These products will be listed in succession in the next 3-5 years However, the competition pattern may be different from that in the United States This can be seen from the current application of domestic hepatitis C DAA in Xianda data v3.2: Table 1 Application of domestic hepatitis C DAA drug company nature company acceptance number molecular name Ababvie jxhl1400170 jxhl1400105 jxhl1400103 abt-450 / ritonavir / abt-267 + dasabuvir film coated tablets NS5A + NS3A + NS5B inhibitor Bi jxhl13000180 bi207127 film coated tablets NS5B inhibitor jxhl1100278 Jxhl0900425 bi201335na capsule NS3 / 4A inhibitor BMS jxhl1400385 jxhl1400061 jxhl1200351 NS5A inhibitor of daclatasvirdihydrochloride tablets jxhl1400384 jxhl1400059 jxhl1200352 NS3 / 4A inhibitor of asunaprevir capsule NS5B inhibitor jxhl1400219 daclatasvir / asunaprevir / NS3 / 4A + NS5A of jxhl1400218 bms-791325 tablets +NS5B inhibitor Jassen jxhl1200319 jxhl1200320 simeprevir capsule NS3 / 4A inhibitor Gilead NS5B inhibitor jxhl1400304 sofosbuvir / ledipasvir tablets NS5B + NS5A inhibitor Mreck unknown granzoprevir / elbasvir, NS5B + NS5A inhibitor of jxhl150130 sofosbuvir / gs-5816 tablets NS 3 / 4A + NS5A inhibitor native dongyangguang cxhl1301427 cxhl1301428 cxhl1301429 imitavir phosphate capsule NS5A inhibitor Taijing medicine cxhl1501084 cxhl1501085 vorarevir capsule NS3 / 4A Geli cxhl1400362 cxhl1400363 asc08, cxhl1500709, cxhl1500710 asc16, NS3 / 4A inhibitor NS5A inhibitor Ginkgo biloba cxhl1300969 cxhl1300970 sirarevir potassium tablets NS3 / 4A inhibitor Caine biological cxhl1401836 cxhl1401837 cxhl1401838 kw-136 capsule (guess) NS5A inhibitor Changzhou Yinsheng Pharmaceutical Co., Ltd Cxhl1501569 cxhl1501569 forbitavir tablets NS5A inhibitor not declared as anfeihewei NS4B inhibitor Zhengda Tianqing unknown bl8030 NS3 / 4A inhibitor ◆ foreign enterprise: clinical research in progress It's definitely that Bi and Janssen were the first foreign companies to start the distribution of oral medication for hepatitis C, but they got up early and caught up late: faldaprevir of Bi applied for clinical treatment in China in 2011, and deleobuvir of NS5B applied for clinical treatment in 13 years How can we combine them in the sound-c3 experiment The sustained virus response rate of gallibavelin to 1b reached 95%, but for patients with major genotype 1a in the United States, the effect was very common Therefore, Bi gave up the comprehensive study of HCV in 2014, and the opportunity to declare in China was lost Janssen, after boceprevir and telaprevir, worked out the second generation of NS3 / 4A Simeprevir, the inhibitor, was listed in the United States in 2013 It was not long before Gilead's sofosbuvir came out It was not easy to slow down to do the DAA alliance Harvoni went on the market immediately, but simeprevir applied for clinical application in China 13 years ago Now it's a little embarrassed to be alone there It's said that Janssen recently bought three more hepatitis C projects, aiming to develop a three drug combination program with shorter medication time and full genotype, but whether he can catch up with Gilead's full genotype program this time, I'm puzzled Among these foreign enterprises, BMS has the most comprehensive layout in the field of hepatitis C: all three single drugs and combination compounds have been declared in China, two approved single drugs daclatasvir and asunaprevir have carried out two clinical studies of combination drugs, and according to the clinical plan published in July 2015, they have put the original asunaprevir + daclassavir The 24 week plan of combined drug use was changed to 12 week plan to shorten the time of combined drug use and ensure the early listing And the triple compound plan was approved in January this year, along with Gilead's harvoni Although abbvie's quadruple compound is listed after harvoni in the United States, it is the first DAA compound approved for clinical use in China Clinical trials began in September 2015, with a period of 12 weeks According to the current progress, it should be completed soon Let's take a look at Gilead and sofosbuvir tablets and their compounds with endless scenery in the United States: Xianda data shows that it applied for ind of sofosbuvir tablets in August 2013, harvoni in September 2014, and velpatasvir / sofosbuvir compounds in June 2015 Gilead's life in China is obviously not at ease in the United States Sofosbuvir not only needs to prevent the sniping of major generic pharmaceutical manufacturers, but also faces the confrontation with abbvie and BMS The advantage of the first DAA joint marketing is self-evident: no injection, only oral administration, and the treatment cycle is half shorter than the original interferon program, so this situation also needs to be contested in the eyes of our onlookers Now that all major manufacturers are in place in China, the application of zepatier, a new drug, has never appeared in China Next, we should see whether MSD has been declared in China If not, we will fight with Gilead and abbvie in the United States thoroughly, if so? That may have to be done slowly Due to the natural advantages of technology and capital experience, foreign enterprises seem to have some opportunities in the use of hepatitis C DAA, but after all, the data of international multi centers can not be directly used in production applications, and it seems that it is an inevitable path to re apply for new drugs and then apply for production, so it seems that domestic R & D enterprises do have a first-line opportunity ◆ domestic enterprises: joint development and preemptive foreign enterprises are tiger and wolf What about domestic relatives? This time, the domestic manufacturers are very ambitious, in order to let the Chinese enjoy the oral hepatitis C therapy, but also show their magic power And for companies that do not have a ready DAA joint program in hand, the most important is: joint! According to the data of Xianda, imitavir, the NS5A inhibitor of dongyangguang, obtained the clinical approval document in November 2014 It can be found on the clinical trial registration platform that phase I trials have been completed However, after all, the single drug can not be compared with each other