May 25, 2020 / Bio Valley BIOON / --Intercept Pharma is a biopharmaceutical company focused on the development and commercialization of novel therapies for the treatment of progressive, non-viral liver diseases. Recently, the company announced that, based on discussions earlier last week, the US Food and Drug Administration (FDA) has notified the company that its advisory committee meeting (AdCom), which is tentatively scheduled for June 9, 2020, has been postponed. The content of the meeting involved the company's drug Ocaliva (obeticholic acid, OCA, obeticholic acid) for the treatment of non-alcoholic steatohepatitis (NASH) caused by liver fibrosis new drug application (NDA). After the news was released, Intercept's stock price plunged 15%.
The delay was due to the FDA ’s need to review the additional data, which the company plans to submit this week. The FDA has indicated that it will establish a new AdCom date in the near future. Intercept now anticipates that the FDA ’s review of the NDA will exceed the target action date of June 26, 2020 in the "Prescription Drug User Fees Act (PDUFA)".
At the end of November 2019, FDA accepted Ocaliva's NDA and granted priority review. The NDA application accelerates approval of Ocaliva for the treatment of fibrosis caused by non-alcoholic steatohepatitis (NASH). At that time, the FDA had designated a PDUFA target date of March 26, 2020.
It is worth mentioning that this delay is not the first time it has been delayed. In fact, it has been postponed 2 times before. The first time was in mid-December 2019. Intercept announced that FDA had notified the company that it had postponed the tentative time of the AdCom meeting to April 22, 2020, and the PDUFA target date would be extended accordingly. The second time was in late March 2020, Intercept once again announced that the FDA delayed the AdCom meeting until June 9 due to the new coronavirus pneumonia (COVID-19) epidemic. This latest delay is also the third delay.
In the past 2 years, many opponents in the NASH field have suffered setbacks, including Gilead Sciences, so Intercept ’s leading position has not changed. The latest delay will not let other competitors prevail.
In the United States, NASH is expected to become the main cause of liver transplantation as soon as 2020. If approved, Ocaliva will be the first method that can be used to treat patients with liver fibrosis caused by NASH. It is particularly worth mentioning that in terms of NASH, OCA is the only research drug granted a breakthrough drug qualification (BTD) by the FDA. It is also the first research drug in the world to enter and be the first to successfully complete Phase III clinical trials .
In December 2019, the positive results of the mid-term analysis of the Phase III REGENERATE study evaluating Ocaliva (obeticholic acid, OCA, obeticholic acid) in the treatment of fibrosis caused by non-alcoholic steatohepatitis (NASH) were published in The Lancet ( The Lancet). This is also the first peer-reviewed publication to evaluate the positive results of a key clinical study of an investigational drug for NASH.
The study was conducted in patients with stage 2 or 3 liver fibrosis due to NASH and evaluated the efficacy and safety of two doses of OCA (10 mg and 25 mg once daily) relative to placebo.
In the main efficacy analysis, at the pre-planned 18-month mid-term analysis, compared with placebo, the daily endpoint of a 25 mg dose of 0CA achieved fibrosis improvement (≥1 stage) and NASH did not deteriorate the primary endpoint (p = 0.0002). In addition, compared with the placebo group, a higher proportion of patients in the 25 mg dose OCA treatment group reached the primary endpoint of elimination of NASH and no worsening of liver fibrosis.
Zobair M. Younossi, professor and head of the medical department of the Innova Fairfax School of Medicine, chairman of the REGENERATE steering committee, and the first author of the article, said: "The first positive Phase III study in the NASH field represents this field of hepatology A real watershed. The anti-fibrosis effect observed after 18 months of OCA treatment in the REGENERATE study is particularly meaningful because fibrosis is the most important histological predictor of liver failure and death in NASH patients.
Ocaliva is a farnesoid X receptor (FXR) agonist. FXR is a nuclear receptor expressed in the liver and small intestine. It is a key regulator of bile acids, inflammation, fibrosis, and metabolic pathways. In the United States, Ocaliva was approved for listing in May 2016 for the treatment of primary biliary cholangitis (PBC). Currently, Ocaliva is being developed for the treatment of many other chronic liver diseases, including NASH, primary sclerosing cholangitis, and biliary atresia.
Non-alcoholic steatohepatitis (NASH) is a severe progressive liver disease caused by excessive accumulation of liver fat that causes chronic inflammation, leading to progressive fibrosis (scarring), which can lead to cirrhosis, liver failure, liver cancer, and death. Advanced fibrosis is associated with a significant increase in liver-related morbidity and mortality in NASH patients.
According to "Nature" magazine, NASH has become the second most common cause of liver transplantation after chronic hepatitis C in the United States, and is expected to become the leading cause in 2020. At present, the NASH market has reached US $ 40 billion.
Source: Gade Chemical Network
