A drug maker in India, Zydus Cadila, has become the first pharma company worldwide to secure a regulatory agency greenlight for a non-alcoholic steatohepatitis (NASH) therapy (Saroglitazar) as the Drug Controller General of India (DCGI) approved the drug.
TrialSite News reviews and breaks down this milestone.
What is NASH?
NASH is a progressive disease of the liver, which starts with fat accumulation in the liver known as Non-Alcoholic Fatty Liver Disease (NAFLD). This condition could progress to cirrhosis and liver failure. It represents a large unmet need and currently no drug is approved for the treatment of the disease anywhere until now. TrialSite News profiled the imminent NASH crisis and the race for a treatment. The disease is highly prevalent, with 10% to 30% of the global population potentially affected. NASH ranks as one of the major causes of cirrhosis, behind hepatitis C and alcoholic liver disease. Liver transplantation is the only option for managing advanced cirrhosis with liver failure.
What is the Prevalence of NASH in India?
The prevalence of NASH in India is estimated to be at nearly 25% of the population.
What is the drug?
Saroglitazar (Lipaglyn) is a drug for the treatment of type 2 diabetes and dyslipidemia with approvals in India. It is indicated for the treatment of diabetic dyslipidemia and hypertriglyceridemia with type 2 diabetes mellitus not controlled by statin therapy. In clinical trial, the drug demonstrated reduction of triglycerides (TG), LDL, cholesterol, VLDL cholesterol, non-HDL cholesterol and an increase in HDL cholesterol—a characteristic mark of atherogenic diabetic dyslipidemia (ADD). Saroglitazar also shows favorable anti-diabetic medication property by reducing the fasting plasma glucose and HBA in diabetes patients.
The drug is a novel-first-in-class therapy that acts as a dual PPAR agonist in the subtypes of the peroxisome proliferator-activated receptor (PPAR). Agonist action at PPAR lowers high blood triglycerides, and agonist action on PPAR-γ improves insulin resistance and consequently lowers blood sugar.
Saroglitazar was launched in India in September 2013 for the treatment of diabetic dyslipidemia and hypertriglyceridemia in patients with type 2 diabetes non controlled by statins alone. It recently received approval for the treatment of Type 2 Diabetes Mellitus. They purport that over the past seven years, over 1 million patients have benefited from the drug.
Clinical Research Backing Indian Authorities’ Decision
The company reports that the drug received positive results in the EVIDENCES II trial, a Phase III liver biopsy trial of Saroglitazar 4 mg versus placebo in Indian patients with NASH. In this study, the sponsor evaluated histological improvement of NASH using liver biopsy at the end of 52 weeks and successfully met primary and secondary endpoints. The sponsor reports that the drug’s use resulted in a significant reduction in liver fat, liver enzymes and disease activity.
In the EVIDENCES I trial—a Phase II clinical trial—Saroglitazar evidenced improvement in liver enzymes and lipids in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Globally, EVIDENCES IV, a Phase II trial of Saroglitazar MG in patients with NASH in the United States, met primary and secondary endpoints. The results of this trial were presented at the Liver Meeting® 2019, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. The company reports that an additional 15 investigator-initiated studies of Saroglitazar have been presented and published in leading scientific journals and conferences.
Who is Zydus Cadila?
Based in India, Zydus Cadila makes its headquarters in Ahmedabad in Gujarat state of Western India. One of the leading “pharmas” in India, they were founded by Ramanbhai Patel (1925-2001) in 1952 to develop generic drugs. Also known as Cadila Healthcare Ltd, they are considered a specialty and generic drug manufacturer. Publicly traded (NYSE: CADILAHC), with almost 20,000 employees (1,400 scientists), they generate nearly $1.8 billion in revenue. The company has grown via merger and acquisition. By 2014, they launched the world’s first adalimumab biosimilar under the brand name Exemptia to one-fifth of the branded drug’s price. The company has developed a considerable pipeline of new product candidates.
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