Hengrui begins to enter the field of fatty liver! The obacholic acid, which was just launched in the United States last year, has been imitated now?!

Source: CPHI pharmaceutical online 2017-08-11 Obaliva (trade name: ocaliva) is a bile acid analogue developed by intercept pharmaceutical company in the United States On May 31, 2016, the drug was approved by FDA to be used in combination with ursodeoxycholic acid (UDCA) for adult patients with primary biliary cholangitis (PBC) who had poor response to UDCA alone or for adult patients with PBC who could not tolerate it alone Recently, the author found a piece of information on the platform of drug clinical trial registration and information publicity, as follows: I don't know It's a shock at first sight It's the domestic R & D first brother Hengrui who carried out this clinical trial The author went in and found more detailed information The first publicity date of this information is July 27, 2017, as follows: (click the small picture to see the big picture) in other words, Hengrui has started to copy the drug that was just launched in the United States last year Is it going to enter the field of fatty liver?! Now I'll show you the truth The only drug approved within 20 years to treat PBC Octalva is a bile acid analogue developed by intercept pharmaceutical company in the United States It is a brand-new activator of fxrx receptor It indirectly inhibits the gene expression of cytochrome 7a1 (CYP7A1) and the synthesis of bile acid Fxris a nuclear receptor expressed in the liver and small intestine and a key link in bile acid, inflammation, fibrosis and metabolic pathway Bond adjustment factor The drug was approved by FDA on May 31, 2016 in combination with ursodeoxycholic acid (UDCA) for the treatment of primary biliary cholangitis (PBC) adults with poor response to UDCA alone, or for the treatment of intolerable PBC adults It is the second drug for primary cholangitis (PBC) patients within 20 years after udac was granted orphan drug approval It was approved by EMA in November of the same year Intercept has the global power of OBC outside Japan, China and South Korea In Japan, China and South Korea, intercept has authorized the drug to Sumitomo pharmaceutical PBC is a rare disease with a worldwide incidence rate of 27/10000 What people are more interested in is the excellent performance of ocholic acid in the treatment of nonalcoholic steatohepatitis (NASH) Nash, with a global potential market of up to 40 billion US dollars, is a chronic progressive liver disease caused by intrahepatic fat accumulation, which can lead to liver cirrhosis, liver failure and liver cell carcinoma Specifically, Nash is only a stage of the development of nonalcoholic fatty liver disease (NAFLD) I specially drew a picture to let you know what kind of disease Nash is Incidence rate of NASH incidence is 2%-3%[1] worldwide, and incidence rate in China is slightly lower than in western countries According to the prediction of evaluatepharme, the global market size of Nash drugs will reach 40 billion US dollars in 2025, and according to IMS data, the conservative market size of liver protecting and enzyme reducing drugs in China will reach 12 billion yuan in 2020 The huge market scale of Nash has attracted many biomedical companies Many biotechnology companies are carrying out preclinical research on their candidate drugs, but most of them are still in a very early stage Obecholate is the world's first Nash drug to enter phase III clinical Because the pathogenesis of Nash is not very clear, the target of Nash is relatively scattered At present, the therapeutic targets and corresponding preparations of NASH are mainly as follows: (1) selective peripheral cannabinoid receptor blocker; (2) peroxisome proliferator activated receptor (PPAR) α / δ double agonist; (3) FXR (farneside x) receptor agonist; (4) cysteine aspartate (5) selective phosphodiesterase (PDE) inhibitors As a FXR receptor agonist, obecholate was awarded a breakthrough drug qualification by FDA in January 2015 It is the first Nash drug in the world to enter phase III clinical practice Phase III research was officially launched in September 2015, which can be said to be the most concerned one among all Nash drugs under research However, the clinical trials of obacholic acid were not successful Previously, the criteria for clinical success of the drug was to reach the composite end point of '1 The proportion of patients whose liver fibrosis level was improved by at least 1 level and Nash did not deteriorate; 2 The proportion of patients whose liver accumulation fat was removed and the fibrosis level did not deteriorate' and the end point index needed to be detected by liver tissue biopsy This very aggressive indicator resulted in the recruitment progress of patients not meeting the expectations In February this year, it was approved by the FDA to change the goal of reaching the composite end point at the same time to just reaching one of the end points In addition, the data of Nash phase II clinical trial in Japan showed that the curative effect of OBC was not up to standard, and only when the dose was increased to 40 mg, there was a significant difference between the two groups Whether obecholate can be used in the treatment of Nash is full of unknown The advantages and disadvantages of Hengrui in developing Nash because PBC is a rare disease and there is no rare disease policy in China, so the author boldly speculates that the ultimate goal of Hengrui is to develop Nash indications of the drug Therefore, the author analyzes the advantages and disadvantages of imitating obecholate acid in treating Nash: advantages and disadvantages Advantages: (1) at present, except Hengrui, no company has applied for the clinical application of the drug; (2) Nash is recognized as the next big market, and China's Nash market will break through 12 billion in 2020; (3) the patent of OBC compound is wo20050829225, which has not entered China, and the patent of OBC and its derivatives entering China mainly focuses on the crystal form and preparation process patent; (4) the biggest competition The efficacy of elafibranor is not good, and other Nash drugs are still in the second stage, about three years behind Obi cholic acid Inferiority Disadvantages: (1) severe pruritus and cardiovascular events of objec acid, which can produce significant pruritus at a dose of 5mg (NASH dose may be increased to 40mg), 3% of patients in the third phase of PBC have serious cardiovascular events; (2) the efficacy of Japanese Nash second phase clinical trial is not up to standard, only when the dose is increased to 40mg, can it be significantly worse than placebo group Different; (3) the cost of one-year treatment of OBC is close to $70000, and no one in China can afford it Under the current drug administration system, the development cost of generic drugs is as high as more than 20 million yuan; (4) the rival is ahead of the competition, and the research progress of Nash of OBC lags behind that of elafibranor, and several competitive drugs may be launched simultaneously with OBC; (5) drug consistency evaluation on generic drugs The pharmaceutical industry has a huge influence, so it may be difficult to bypass the crystal types involved in compound patents All of the above are my family's opinions Readers are welcome to leave comments and discuss the controversial places at any time! Attachment: Nash R & D pipeline (as of August 2017)