Public Release:  New phase II study supports potential of gs-9450 as new treatment option for steatohepatitis

Results show highly significant dose dependent response

European Association for the Study of the Liver

Vienna, Austria, Thursday 15 April: Results from a multinational phase II study presented today at the International Liver CongressTM 2010 have shown that treatment with the caspase inhibitor GS-9450 can reduce markers of liver damage in patients with non-alcoholic steatohepatitis (NASH - the most serious form of non-alcoholic liver disease) as demonstrated by reduced levels of alanine (ALT) and aspartate aminotransferases (AST), hepatic enzymes that indicate cell damage.

GS-9450, a potent inhibitor of caspases-8, -9 and -1, the intra-cellular proteins that initiate programmed cell death (or cell suicide, also known as apoptosis) in damaged cells, is a potential new treatment option for patients with NASH - a disease characterised by fat build-up in liver cells with subsequent inflammation resulting in accumulation of scar tissue (fibrosis), cirrhosis and eventual liver failure.

Professor Fabio Marra of the EASL scientific committee commented: "It is encouraging to see that GS-9450-associated reduction of apoptosis and cell damage seen in animal models has translated to a significant patient population, and seems to be consistent with a good tolerability profile in patients from a variety of countries. Further studies are needed to evaluate the action of this therapy on histology and to confirm the drug's efficacy and safety in larger patient populations."

In this double-blind, parallel-group study, patients (n=124, principally male, mean age 45 years, with Body Mass Index (BMI) of >30kg/m2) with biopsy-proven NASH were randomised to receive 1, 5, 10 or 40mg GS-9450 or placebo once daily for 4 weeks. After 4 weeks on treatment, patients in the 40mg treatment group experienced the greatest reduction in ALT and AST levels.

At week four, linear regression of ALT versus GS-9450 dose was highly significant (p<0.0001) with 35% achieving ALT levels within the normal range (7-56 U/L ) compared to 0% at study baseline, and 48% achieving normal levels of AST (5-40 U/L1) compared to 20% at baseline. Placebo treatment showed no meaningful change for ALT or AST.

Additionally, the on-treatment measure of cytokeratin-18 caspase cleavage fragments (proteins that act as markers for liver cell death) declined in the 10 and 40mg dose groups (median baseline and week four values respectively were 540 and 445 U/L in the 10mg group and 562 and 386 U/L in the 40mg group), although no dose-related response was seen.

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About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts as members and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European Liver policy.

EASL's work continues throughout the year with numerous events and initiatives, including:

  • The International Liver CongressTM which lasts several days and attracts upwards of 7,500 participants
  • EASL meetings including Monothematic and Special conferences, Post Graduate courses and other EASL endorsed meetings that take place throughout the year
  • EASL Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly with a readership of over 40,000
  • Presenting new initiatives for European liver policy change

About The International Liver CongressTM 2010

The International Liver Congress™ 2010, the 45th annual meeting of the European Association for the study of the Liver, is being held at the Reed Messe Wien congress center, Vienna, Austria from April 14th-18th, 2010. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

References:

1Ratzui V. et al., Safety, Tolerability and preliminary activity of GS-9450, a selective caspase inhibitor, in patients with non-alcoholic steatohepatitis (NASH). Abstract presented at The International Liver CongressTM 2010

2Liver Blood Tests. Available at http://www.medicinenet.com/liver_blood_tests/page2.htm accessed 08.04.10

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