Cadila Healthcare, also known as Zydus Cadila, said it has started enrolling patients in a trial that can potentially yield the first FDA approved treatment for NASH or non-alcoholic fatty liver disease with inflammation.
Fatty liver disease, caused by the deposition of fat in the liver, is divided into alcohol-related and non-alcohol related. Within non-alcoholic fatty liver disease, there are two sub-types — ones with inflammation of the liver, and those that also cause inflammation of the liver (NASH).
It is believed that about 25% of adults have non-alcoholic fatty liver disease, and 5-10% of the adults worldwide have the variant which causes liver inflammation (NASH).
Unlike ‘regular’ non-alcoholic fatty liver disease, NASH comes with additional symptoms that make more dangerous. These include lobular inflammation, hepatocyte ballooning with or without pericellular fibrosis and MalloryDenk bodies.
This makes NASH progressive, and the disease can often lead to liver cirrhosis, liver cancer and need for liver transplant or death.
There is currently no drug approved to treat this disease in the US.
“As there is currently no drug approved for the treatment of NASH in the USA, this life threatening liver disease is a high unmet medical need,” Zydus Cadila said, announcing the start of the Phase 2b study.
Zydus’ Saroglitazar Mg has an ‘Orphan Drug Designation’ and ‘Fast Track Designation’ from the US FDA, which means that it is eligible for faster processing than usual and longer exclusivity protection.
However, these designations are only as a treatment for primary biliary cholangitis, which refers to the condition in which the bile ducts inside the liver become injured, inflamed, and eventually permanently damaged. The drug also has orphan status from the European Medicines Agency for the same condition.
“We stand encouraged that the findings from the earlier EVIDENCES-IV Phase 2 clinical study have been published as original article by Samer et al along with the editorial by Prof. Sven Francque, M.A. a leading hepatologist from Belgium in the October edition of Hepatology,” said the Indian company.
The new, Phase 2(b) study is being carried out under authorization from the US FDA.
It is a prospective, multi-centre, randomized, double-blind, placebo-controlled clinical trial designed to evaluate efficacy and safety of Saroglitazar Magnesium in subjects with Non-Alcoholic Steatohepatitis (NASH) and Fibrosis.
It will be led by Prof. Naga Chalasani, Interim Chair, Department of Medicine, Indiana University School of Medicine and Prof. Arun J Sanyal, Division of Gastroenterology, Virginia Commonwealth University as co-Principal Investigators.
The EVIDENCES-X trial will randomise 240 subjects in a 1:1:1 ratio to Saroglitazar 2 mg, Saroglitazar 4 mg or Placebo and study the primary endpoint “Resolution of steatohepatitis with no worsening of fibrosis” over a period of 76 weeks.
The secondary end-points will include improvement in liver fibrosis with no increase in NAS for ballooning, inflammation or steatosis, 2 points improvement in NAS, Improvement in steatosis, ballooning, inflammation and fibrosis from liver biopsy, Histological score changes in steatosis, ballooning, inflammation and fibrosis.