Summary of research progress in the field of liver diseases (12.01)
December 01, 2017 Source: WuXi PharmaTech
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];1. Chinese researchers to detect changes in biomarkers in HBV-related diseases
More than 2 billion people worldwide are infected with hepatitis B virus (HBV), and it is estimated that 50 million new infected people will be added each year. Most of the 240 million people with chronic hepatitis B (CHB) are from Asia and Africa. Chronic hepatitis B may develop into cirrhosis and liver failure, which is the main cause of hepatocellular carcinoma (HCC). Therefore, monitoring disease progression associated with HBV infection is an important clinical issue for early treatment of liver disease.
When liver damage occurs, the enzymes accumulated in the liver cells are released into the blood circulation, causing changes in the concentration in the serum. Therefore, changes in hepatic cytokines appearing under liver stress may reflect the state of the liver, possibly monitoring. HBV-related diseases provide a non-invasive and easy to implement means. Recently, a team led by researchers from the Sixth People's Hospital affiliated to Shanghai Jiaotong University published a paper in "Scientific Reports", which reported changes in circulating FGF21 in HBV-related diseases, and explored the potential of FGF21 as a biomarker for liver disease.
â–² Shanghai Sixth People's Hospital (Source: Shanghai Sixth People's Hospital official website)
Fibroblast growth factor 21 (FGF21) is a stress-induced hormone in the liver, and many evidence from animal and clinical studies indicate that FGF21 is involved in a variety of liver stimuli. In this study, the investigators investigated 33 patients with acute hepatitis B (AHB), 75 patients with CHB, and 66 patients with advanced CHB, including cirrhosis, chronic acute liver failure (ALCF), and HCC. Circulating FGF21 levels in their serum were measured and compared to 200 control subjects with comparable age and body fat percentage (BMI). The researchers found that the level of FGF21 in patients with AHB was significantly higher than in healthy people and quickly returned to normal levels after treatment. The level of FGF21 reflects the degree of liver damage caused by AHB. However, serum FGF21 levels in patients with CHB, particularly in patients with cirrhosis, are reduced and are associated with liver protein synthesis. Serum FGF21 in CHB patients increases with the onset of ACLF. The researchers also found that serum FGF21 was significantly increased in CHB patients who developed HCC. These findings may provide important information for monitoring tumor formation in patients with CHB and improve the early diagnosis and treatment of patients with liver disease.
2. The mid-term results of the clinical trial of new drugs for hepatitis D are gratifying
Recently, Hepatera and its partner MYR GmbH announced the positive interim results of the clinical phase 2b trial of "MYR 202", which investigated the role of Myrcludex B in chronic hepatitis D virus (HDV) infection.
Hepatitis D is one of the most serious viral hepatitis caused by HDV infection. It only occurs in patients who have been infected with hepatitis B virus (HBV), which can seriously aggravate liver damage and accelerate the incidence of liver fibrosis and liver cancer. . Approximately 4.3-5.7% of patients with chronic hepatitis B carry HDV. In recent years, chronic hepatitis B patients have benefited from advances in antiviral therapy, but hepatitis D, the most aggressive hepatitis, still lacks treatment and medical needs are huge.
Myrcludex B is the best-in-class drug for the treatment of chronic HBV and HDV infection. The drug inhibits the newly identified HBV receptor on the surface of hepatocytes, thereby preventing the virus from infecting healthy cells and spreading in the liver. Myrcludex B showed good safety and antiviral activity in both animal models and proof-of-concept tests.
The MYR 202 trial enrolled 120 subjects in 15 centers in Russia and Germany and completed an active treatment phase. After 24 weeks of treatment, Myrcludex B showed excellent safety without major drug-related adverse events or treatment interruptions. Patient compliance with treatment is very high. All doses of Myrcludex B subjects achieved a primary endpoint of a decrease in HDV RNA of more than 2 log10 or negative. In the 10 mg Myrcludex B dose group, 76.6% of patients achieved a primary endpoint, compared with 3.3% in the control group; the mean HDV RNA decreased by 2.7 log10 in the 10 mg dose group compared to 0.18 log10 in the control group. Significant biochemical reactions were observed in the Myrcludex B treatment group, but not in the control group. At week 24, 40% of patients in the 10 mg dose group achieved normalization of ALT (ALT is the most common enzyme in the liver), compared with 6.6% in the control group. The median ALT of the 10 mg dose group and the control group were 43 U / L and 76 U / L, respectively. All differences between Myrcludex B and the control group were statistically significant. More importantly, a decrease in liver stiffness and a decrease in intrahepatic HDV RNA levels were observed in the Myrcludex B group. The interim results of the trial were presented at the annual meeting of the American College of Hepatology (AASLD) by Professor Heiner Wedemeyer of Hannover Medical School.
“This is by far the largest controlled trial of chronic hepatitis D,†Professor Wedemeyer said. “Patients with advanced disease (50% cirrhosis) and no other treatment options are included in the trial. These results may be given Creating an effective therapy for these hopeful patient groups is an important milestone in the treatment of hepatitis D."
3. The Data Safety Inspection Committee released the clinical phase 3 trial of elafibranor
Recently, Genfit issued a statement announcing that the Data Security Monitoring Committee (DSMB) has issued a new positive recommendation, recommending that the “RESOLVE-IT†clinical phase 3 trial continues without modification. Genfit is a company that specializes in the development of therapeutic and diagnostic solutions for metabolic and inflammatory diseases, with a particular focus on liver and digestive tract diseases.
The RESOLVE-IT Phase III study is a study of the efficacy and safety of elafibranor 120 mg or placebo in patients with nonalcoholic steatohepatitis (NASH) and fibrosis. It is a multicenter, randomized, double-blind, placebo-controlled, dual-arm study.
Nonalcoholic steatohepatitis (NASH) is a liver disease in which fat accumulates in the liver and can cause liver fibrosis and cirrhosis. It is estimated that NASH will soon become the most common cause of advanced liver disease, and these patients usually require a liver transplant. There are currently no approved treatment options for NASH, and there is still a huge medical need to be met in this area. NASH is considered a chronic condition and patients may need to take medication for long periods of time, so safety is critical for any drug candidate.
Elafibranor is a once-a-day oral medication that is a first-of-its-kind drug that works through the dual peroxisome proliferator-activated alpha/delta pathways. Developers believe that elafibranor can affect many aspects of NASH, including inflammation, insulin sensitivity, lipid/metabolic characteristics, and liver biomarkers.
The positive results of the DSMB released safety assessment enabled GENFIT to continue to actively recruit patients for the RESOLVE-IT trial. Currently, more than 800 patients have been randomized in this trial.
Reference material
[1] Diverse Changes of Circulating Fibroblast Growth Factor 21 Levels in Hepatitis B Virus-Related Diseases
[2] Maxwell Biotech Venture Fund's Portfolio Company Hepatera LLC Announces Positive Interim Results of Phase IIb Clinical Program of Myrcludex B
[3] GENFIT: Positive Outcome From the 18-month Pre-Planned Safety Review by the DSMB, in RESOLVE-IT Phase III Clinical Trial With elafibranor
Original Title: Summary of Research Progress in the Field of Liver Diseases (No. 29)
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