The green light from the Drug Controller General of India (DCGI) makes saroglitazar the first drug in the world approved for this indication.
“We are happy that our efforts to discover and develop a novel drug for patients living with NASH, an unmet health care need globally, have been successful,” said Pankaj Patel, the chairman of Zydus Group. “Saroglitazar will provide hope and new lease of life for millions of patients in India suffering from NASH.”
The approval is based on a phase III liver biopsy trial of saroglitazar 4 mg vs. placebo in Indian patients with NASH. At the end of 52 weeks, the histological improvement of NASH using liver biopsy was evaluated. The trial succeeded in meeting its primary and secondary endpoints, showing saroglitazar demonstrated a significant reduction in liver fat, liver enzymes and disease activity.
Zydus Cadila described saroglitazar as “uniquely poised” due to its dual PPAR alpha and gamma properties, which reduce co-morbidities (dyslipidemia, hypertriglyceridemia, diabetes mellitus) and cause NASH resolution.
Saroglitazar was launched in India in September 2013 for the treatment of diabetic dyslipidemia and hypertriglyceridemia in patients with type 2 diabetes not controlled by statins alone. In January 2020, Saroglitazar received an approval for the treatment of type 2 diabetes mellitus.
Over the last seven years, Zydus Cadila estimates more than 1 million patients have benefited from the drug. This latest approval could see it reaching many more, as the pharma company estimates that the prevalence of NASH in India alone is estimated to be nearly 25% of the population. It is also a highly prevalent disease across the globe, with a strong presence across most populations.
Zydus Cadila did not reply to queries from BioWorld regarding its plans for other markets.
However, in a conference call in May 2019, Sharvil Patel, the managing director of Zydus, mentioned that there was a phase III trial for NASH underway in the U.S. It is unclear as to whether the India approval might help to expedite approval elsewhere.
NASH is one of the major causes of cirrhosis and liver failure, just behind hepatitis C and alcoholic liver disease. The progressive disease of the liver, which starts with fat accumulation known as nonalcoholic fatty liver disease (NAFLD), is a leading cause of liver failure and transplants.
There have not been any treatments approved so far, though several companies around the world are rushing to develop their NASH candidates.
"U.S. biotech companies are still conducting phase II trials," Kai Sun, an analyst from Shanghai-based Green River Investment, told BioWorld of the state of competition from the West.
Shenzhen, China-based Hightide Therapeutics Inc.’s HTD-1801 is also in phase II trials in the U.S.
In February, NGM Biopharmaceuticals Inc., of South San Francisco, received positive results from an adaptive phase II study evaluating the use of aldafermin (formerly NGM-282) in patients with biopsy-confirmed NASH.
New York-headquartered Intercept Pharmaceuticals Inc. is seen as holding the lead in the race, as it has positive results from a large phase III trial for its obeticholic acid. However, it recently stated that the approval deadline is now set for June 26 rather than March 26.
U.S.-China startup Terns Pharmaceuticals Inc. also recently stated that its TERN-101 has demonstrated safety and potency in a phase I study in the U.S. “These results indicate that TERN-101 has best-in-class potential and gives us great confidence as we prepare to initiate phase II clinical studies with NASH patients in mid-2020,” said Erin Quirk, the chief medical officer of Terns.
In China, Sunshine Lake Pharma Co. Ltd.’s HEC-96719, Chia Tai Tianqing Pharmaceutical Holdings Co. Ltd. (CTTQ)’s TQA-3653, and Guangdong Zhongsheng Ruichuang Biological Technology Co., Ltd.’s ZSP-0678 are in phase I trials. Meanwhile, CTTQ’s TQA-3526 and Zhongsheng Ruichuang’s ZSP-1601 are in phase Ia trials. Hangzhou-based Sciwind Biosciences Co. Ltd. is also working on a NASH drug candidate.
In February, Hangzhou-based liver disease specialist Ascletis Pharma Inc. said Chinese regulators have accepted its application to start clinical trials for its ASC-41 to treat NASH.
“We expect to start the clinical trial in the third quarter of 2020,” a media spokesperson for Ascletis’ told BioWorld, adding that the company believes that ASC-41, an oral thyroid hormone receptor beta (THR-beta) agonist, could be promising for the treatment of NASH in combination with its ASC-40, an oral fatty acid synthase inhibitor.
All in all, the field for NASH treatment is looking remarkably busy, with numerous candidates now lining up to provide treatment solutions for the previously untreatable condition.