Evogliptin

NASH is similar to cirrhosis of the liver but occurs in people that drink little or no alcohol. It is related to the obesity epidemic and affects at least three to five percent of the adult population worldwide. Many believe that combination therapies will be the best way to approach treating NASH, because it has several components. Pfizer and Novartis inked a non-exclusive clinical development deal to investigate one or more combination therapies for non-alcoholic steatohepatitis (NASH). NASH is similar to cirrhosis of the liver but occurs in people that drink little or no alcohol. It is related to the obesity epidemic and affects at least three to five percent of the adult population worldwide. The two companies will run both non-clinical and Phase I clinical trials of Pfizer’s therapies, including PF-05221304, an Acetyl CoA-Carboxylase (ACC) Inhibitor, PF-06865571, a Diacylglycerol O-Acyltransferase 2 (DGAT2) Inhibitor, and PF-06835919, a ketohexokinase (KHK) inhibitor, with Novartis’ tropifexor, a non-bile acid, Farnesoid X receptor (FXR) agonist. Many believe that combination therapies will be the best way to approach treating NASH, because it has several components, including fatty liver, inflammation, liver cell scarring, and fibrosis. “This is an exciting collaboration with Novartis that furthers our approach to this complex disease by exploring different and potentially complementary mechanisms of action,” said Morris Birnbaum, senior vice president and chief scientific officer, Pfizer Internal Medicine, in a statement. “Our research in NASH dates back more than a decade and stems directly from how we have developed medicines to address conditions that put patients at risk for NASH, including Type 2 diabetes and cardiovascular disease. We are confident that by drawing from our history and deep understanding of the close interplay between metabolic, inflammatory and cardiovascular conditions, we can potentially uncover treatments that truly meet patient needs.” The global market for NASH drugs is estimated to be $20 billion to $35 billion. There are no specific approved therapies. Two smaller companies in particular, Intercept Pharmaceuticals and France’s GENFIT , are leading the way. In February, Intercept launched its REVERSE Phase III clinical trial of obeticholic acid in patients with compensated cirrhosis due to NASH. “NASH is poised to soon eclipse hepatitis C as the leading reason for liver transplants in the U.S. and Europe, so there is an urgent need for effective therapies that can reverse fibrosis and cirrhosis,” stated Mark Pruzanski, Intercept’s president and chief executive officer, in a statement at the time. “OCA is currently the only FDA-designated Breakthrough Therapy in development for NASH and, with our Phase III trials REGENERATE and REVERSE underway, we are on track to bring the first approved therapy to NASH patients with fibrosis and cirrhosis who are at greatest risk of liver failure.” In June, Genfit released preclinical data for its drug elafibranor in anti-tumor activity in the context of NAFLD/NASH-induced hepatocellular carcinoma (HCC). And in April, the Data Safety Monitoring Board (DSMB) released a positive recommendation for the continuation of its RESOLVE-IT Phase III clinical trial of elafibranor in NASH. Another big company, Allergan , has made NASH a research priority. In September 2016, Allergan acquired San Francisco-based Tobira Therapeutics for its NASH pipeline. Tobira had two complementary development programs, Cenicriviroc (CVC) and Evogliptin, for NASH. In the same month, Allergan acquired Akarna Therapeutics , located in San Diego, for its NASH programs. Allergan also has AKN-083 in its pipeline for NASH. Evogliptin is a DPP-4 inhibitor that targets metabolic abnormalities. AKN-083 is a highly differentiated non-bile acid FXR agonist. Other companies working on NASH include Novo Nordisk , Shire , Galmed Pharmaceuticals and Conatus Pharmaceuticals .

March 3, 2017 By Mark Terry , BioSpace.com Breaking News Staff Swiss-based Novartis is believed to be in talks to buy France-based Genfit , according to insider sources. Genfit took a big jump at the news, rising from 21.29 Euros on March 1 to a current trading value of 28.92 Euros. The current exchange rate is 1.06 U.S. dollars to one Euro. Genfit headquarters are in France, with a U.S. site in Cambridge, Mass. The company is focused on metabolic diseases related to obesity. Its lead pipeline product is elafibranor (GFT505) for nonalcoholic steatohepatitis (NASH) to prevent fibrosis progression. It is currently being studied in a Phase III trial, RESOLVE-IT. NASH, sometimes called the “silent liver disease,” resembles alcoholic liver disease, but appears in people who drink little or no alcohol. However, it can be quite severe and lead to cirrhosis. According to the National Institute of Diabetes and Digestive and Kidney Diseases , NASH affects 2 to 5 percent of people in the U.S. There are currently no specific treatments aside from weight loss, increased physical activity, and avoiding alcohol and unnecessary medications. Genfit has projected the worldwide market for NASH treatments to exceed $30 billion. However, some analysts believe that’s unrealistic due to an assumption that 85 percent of the NASH population could be treated, which equates to a global NASH market size of around $30 to $40 billion. There is a range of severity in NASH patients, and the advanced fibrosis stage (F3/F4) is when patients generally note symptoms that make them feel poorly and want treatment. A more conservative estimate for the addressable NASH patients is about 6 to 10 million patients, which would make the global NASH market size at least $10 billion. Dublin-based Allergan made several strategic acquisitions last year in the NASH market, buying San Francisco-based Tobira Therapeutics for a deal that could add up to $1.695 billion. Tobira has two complementary development programs, Cenicriviroc (CVC) and Evogliptin, for NASH. And also in September, it acquired Akarna Therapeutics , headquartered in San Diego. Akarna’s lead candidate is also a NASH product. With a wide-open market and no treatments, many companies are showing an interest in the NASH market. Other leaders in the area include Intercept , Gilead , Novo Nordisk , Shire , Galmed and Contus . There were rumors last year that Novartis was considering buying Intercept. In a February 8 report Genfit indicated, “Subject to satisfactory clinical results obtained during the first stage of this study (RESOLVE-IT) in a first group of approximately 1,000 patients, which GENFIT anticipates can be recruited by the Summer of 2017 and the authorization of the regulatory agencies, a conditional marketing authorization could be obtained for elafibranor in NASH during the course of the second half of 2019 or first half of 2020.” The company also received approval from the U.S. Food and Drug Administration to start a Phase II trial of elafibranor in Primary Biliary Cholangitis (PBC). PBC is a rare, chronic disease characterized by the gradual destruction of the liver’s bile ducts, which inhibits the liver’s ability to clear the body of toxins. It can lead to liver tissue scarring, in other words, cirrhosis. The first patient is expected to be recruited in Spring 2017. Genfit is also exploring potential combination therapies using elafibranor in NASH with other Genfit programs, as well as other products in development for NASH. The company also has other biomarkers under development for the diagnosis of NASH. The current approach to a definitive diagnosis is through expensive and invasive liver biopsies.