M0002 Progresses To Phase IIb Trial Following Positive Results In Cirrhotic Ascites

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials
Article Date: 04 Jul 2008 - 0:00 PDT

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Movetis NV, a European specialist pharmaceutical company, announced that M0002 is progressing to phase IIb following positive results of a phase IIa multiple-dosing trial for the treatment of ascites, the accumulation of fluid in the abdomen in patients with liver cirrhosis resulting from liver conditions such as hepatitis C, hepatitis B or alcoholism.

M0002 is an orally-active selective vasopressin 2 receptor antagonist and a member of a new class of compounds, known as aquaretics, which inhibit water reabsorption from the renal collecting duct. The compound induces free water clearance without loss of sodium.

The randomized, double blind, placebo controlled, dose-titration study explored the safety, tolerability, pharmacokinetic profile and efficacy of M0002 in cirrhotic subjects with ascites and hypo- or normonatraemia. It was conducted in Belgium at multiple centers and enrolled 15 patients who were treated once daily with drug or placebo for 15 days.

"The data are encouraging," states Prof Dr. F. Nevens, Chief of Hepatology at the University Hospital in Leuven and principal investigator of the trial. "M0002 was very well tolerated and proved to have a good safety profile. No unexpected side-effects were seen in these very ill patients. The pharmacokinetic profile was in line with expectations."

Although a small number of patients were included in the study, a trend towards more stabilized and normalized plasma sodium levels was seen in those treated with M0002.

Remi Van den Broeck, Chief Development Officer of Movetis, said, "We are delighted with the promising results from the dose-titration trial. We will begin patient recruitment shortly for a Phase IIb dose-finding study. At Movetis we are committed to improving the lives of patients with ascites and we believe that M0002 may eventually offer hope to many who suffer from the condition."

About cirrhotic ascites

Cirrhosis is a consequence of chronic liver disease, most commonly caused by alcoholism and hepatitis B or C. It is characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules, leading to progressive loss of liver function. Ascites, the accumulation of fluid in the peritoneal cavity, is a major complication of cirrhosis. The development of ascites is a significant marker in the progression of cirrhosis as it is associated with high mortality over two years, and signifies the need to consider liver transplantation as a therapeutic option.

Dr. F. Wong, Associate Professor of Medicine at Toronto General Hospital, when asked for comment on the disease and on the therapeutic options, said:

"The development of ascites, or fluid in the abdominal cavity, is a common complication of liver cirrhosis. Its onset signifies the progression of liver cirrhosis into the decompensated stage with worsening of prognosis to 50% survival in 2 years. The treatment of ascites includes the use of dietary sodium restriction, diuretics (loop diuretics and or spironolactone) and large volume paracentesis. The continued use of diuretics is limited by the development of complications such as electrolyte abnormalities, and many patients eventually become diuretic resistant, that is, the use of diuretics is no longer resulting in a reduction of ascites. Such patients are totally dependent on large volume paracentesis as a means of controlling the ascites. The use of paracentesis is inconvenient to the patient and requires significant medical manpower."

Both Prof. Wong and Prof. Nevens agree that there is an urgent need for newer and effective drugs to better manage cirrhotic patients with ascites.

About M0002

M0002 is a selective vasopressin 2 receptor antagonist and is a member of a new class of compounds - aquaretics - that produce significant diuresis without the loss of electrolytes. Conventional diuretic drugs, which are currently used to treat ascites, have the drawback that they promote the excretion of both salt and water, leading to possibly symptomatic hyponatremia (abnormally low concentration of sodium in the blood). In contrast, M0002 primarily increases free water clearance. This important differentiation could potentially offer clinical advantages in the treatment of cirrhosis and other disorders caused by water-retention.

About Movetis

Through a clear focus on gastroenterology (GI), Movetis seeks to improve the lives of millions of patients - both adults and children - by discovering, developing and ultimately commercialising innovative treatments targeting GI conditions with a high unmet medical need. Movetis NV - founded in Belgium in December 2006 - aims to become a leading European specialty pharmaceutical organisation focused on GI diseases. Movetis has a broad GI portfolio with one product in preregistration, two products in clinical development, one product ready to move into clinical development and four in preclinical development, all addressing important areas including chronic constipation, ascites, paediatric reflux in infants, diabetic gastroparesis, specific subgroups of patients with severe forms of irritable bowel syndrom or dyspepsia. In addition, Movetis has rights to a large library of qualified lead compounds with potential for development in different GI indications and access to know how for compounds in secretory diarrhoea. The current portfolio has been licensed from Janssen Pharmaceutica NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J) companies.

http://www.movetis.com