Nonalcoholic steatohepatitis (NASH) is an extremely advanced form of nonalcoholic fatty liver disease, defined as the appearance of steatosis associated with inflammation and hepatocyte damage, leading to advanced liver fibrosis, cirrhosis, liver failure and The production of liver tumors. According to an article in Nature in 2017, NASH has become the second most common cause of liver transplantation in the United States following chronic hepatitis C and is expected to be the leading cause in 2020.
The pharmaceutical market research institute ResearchAndMarkets has released a report that the NASH market is $729 million in 2016 and is expected to reach $20.576 billion by 2025. The compound annual growth rate (CAGR) for the 2017-2025 period will reach a staggering 46.1%.
Despite the urgent medical needs, no drugs have been approved for NASH treatment so far. Fortunately, since Intercept announced the data on the drug Nacaliva treatment of NASH clinical projects in 2014, there have been many followers in this field.
EvaluatePharma recently stated that 2019 will be a key year for NASH new drug development, with four teams in the field receiving critical clinical research data, including Intercept (see table below), which will also help each Large companies lay the future business position in the NASH field.
NASH's new drug research and development field has not been smooth, and the recent NASH projects related to Gemphire and Shire have all caused problems. First, last Wednesday, the FDA did not allow Gemphire to initiate a long-term clinical study of gemcabene. The news was that the sub-chronic toxicology research data was mature, and the news caused the company's share price to plummet 51%. Recently, the company announced the cancellation of a clinical study of gemcabene, a pediatric fatty liver, due to an unexpected increase in liver fat, which caused the stock price to plunge by 60%. Shire has quietly abandoned the volixibat clinical project last month, but did not give any reason, the drug has been in Phase II clinical development.
However, the above unfavorable news did not dampen the overall enthusiasm of investors in the NASH field, because there are two other potential NASH assets in the field of vision, namely Malmed aramchol and Madrigal MGL-3196.
Who will be the first to land in the market?
At present, the industry believes that the first NASH drug will be born in Intercept's Ocaliva and Gilead's selonsertib. In 2019, the two parties will publish interim data on their Phase III clinical studies, and both parties hope to submit accelerated approvals to the US FDA.
In the case of Intercept, analysts point out that Ocaliva needs to achieve at least one surrogate endpoint in the phase III clinical study REGENERATE: NASH remission and no fibrosis worsening or fibrosis relief and no NASH deterioration. In addition, Intercept must also prove the safety of Ocaliva, because the drug has been exposed to the risk of death and severe liver damage in the treatment of primary biliary cholangitis last September, so high doses of NASH will be closely watched. . In addition, Ocaliva failed in a Japanese NASH study and also attracted secondary attention from investors.
It is worth noting that the biggest design differences in the key clinical studies listed above are the time points of NASH score and fibrosis change detection.
This is very important, especially considering that Genfit's elafibranor failed to reach the primary endpoint of fibrosis and NASH remission at 12 months in phase II clinical trials. In addition, Aijian cenicriviroc was found in a phase II clinical study published in 2017. There was no significant difference in reducing fibrosis and no NASH deterioration. The drug is currently in phase III clinical trial, which is also the 12-month end point of the test. However, some investors suggested that Ai has the potential to modify the clinical design and focus on the patient population with a higher NASH baseline score.
The industry is looking forward to the announcement of the above key clinical research data. And investment bank analyst Bernstein reminded that the key focus now is to establish strict clinical data.
