Therapeutic Areas

About Liver Disease
Dedicated to Improving the Lives of Patients with Liver Diseases

Liver diseases represent a major societal burden impacting millions of people and costing national healthcare systems billions of dollars. Despite recent increased interest from the pharmaceutical industry and supportive governmental actions, the therapeutic options for liver disease patients remain limited. In particular, little progress has been made to treat life-threatening end-stage liver diseases, such as cirrhosis and Acute-on-Chronic Liver Failure (ACLF).

There is an urgent need to find new innovative therapeutic solutions to fight the alarming increase in morbidity and mortality due to liver disease. 

  • Globally, an estimated 1.5 billion people suffer from chronic liver disease, claiming 2 million lives each year.1,2
  • Liver disease is the 11th leading cause of death globally with alarming increase in the total annual deaths.2
  • In the US, liver disease is the 5th leading cause of premature and the most prevalent cause of death between men and women 35-55 years old.3
  • Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the US, affecting one-quarter of the population.4

In the broad spectrum of liver diseases, Versantis sets itself the objective of first addressing the orphan-designated life-threatening end-stage liver diseases where the medical need is the most critical.

1. Moon AM et al., Clin Gastroenterol Hepatol 18 (2020)
2. Asrani SK et al., J Hepatol 70 (2019) 

3. CDC Center for Disease Control and Prevention, www.cdc.gov 
4. Younossi Z et al., Nat Rev Gastroenterol Hepatol 15 (2018)

Acute-on-Chronic Liver Failure (ACLF)

ACLF is a syndrome characterized by an abrupt life-threatening worsening of a pre-existing advanced chronic liver disease (e.g., cirrhosis) resulting in liver and extrahepatic organ failure (brain, kidneys, cardiovascular, and respiratory). The cascade of multiple organ failure and the development of a neuropsychiatric condition called hepatic encephalopathy represent major complications in patients with ACLF, who can rapidly progress into coma and death. 

ACLF is an underserved medical condition, which, despite best possible available care, is associated with high short-term mortality (23% - 74% mortality at 28 days, depending on severity grade)1. Every year, an estimated 137'000 patients are hospitalized with ACLF in the US, and the average cost of hospitalization exceeds $50'000 per patient. The incidence is growing at epidemic rates due to an aging population and a higher prevalence of diabetes, obesity, NAFLD, as well as alcohol and drug-induced liver injury.

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  • ACLF represents a significant burden to the healthcare system: hospitalization costs are >3.5-fold higher than for patients with cirrhosis.2
  • Hospital stay for ACLF patients is 16 days (vs. 7 days for cirrhosis).2
  • Global prevalence and mortality of ACLF are high. ACLF represents 35% of hospitalized patients with decompensated cirrhosis.3
  • ACLF is a rare disease and VS-01 received the Orphan Drug Designation for this indication by the FDA.
  • If recognized early, ACLF can be reversed by appropriate multi-organ supportive care.4
  • Liver transplantation represents the only definitive therapeutic option for patients with ACLF, however, patients often face delisting1 and 50% - 70% of patients die while waiting for a liver graft.
  • The mean hospital charge per admission of an ACLF patient ranged from $54’000 to $180’000 in the USA. These costs grew  5-fold in the past 10 years.2,5

1. Arroyo V et al., Nat. Rev. Dis. Primers 2 (2016)
2. Allen MA et al., Hepatology 64 (2016)
3. Mezzano G et al., Gut (2021)
4. A Alam et al., J Biomed Res 31 (2017)
5. Leffingwell S et al., Am J Transplant 16 (2016)

Urea Cycle Disorders (UCDs)

UCDs are a family of rare genetic disorders characterized by deficiencies of one of six enzymes involved in the urea cycle. This deficiency leads to high levels of neurotoxic ammonia in the blood (i.e. hyperammonemia). Currently, neonate screening fails to detect most UCDs and the majority of patients are first diagnosed neonatally, at clinical presentation with symptoms such as lethargy and periodic vomiting. Hyperammonemia rapidly progresses to coma and death if not treated within days. Therapies aimed at reducing plasma ammonia concentration have to be implemented as early as possible to avoid severe neurological complications.

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  • UCDs are rare diseases affecting about 1'000 newborns yearly in the EU and US which translates to between 1 in 10'000 and 1 in 35'000 births.1,2
  • UCDs show high mortality: 25% died and only 20% of all patients have a "normal" outcome.3,2 The prognosis is linked to blood ammonia level and the rapidity of its reduction.
  • The treatment of severe neonatal forms relies on specific neonatal hemodialysis and/or hemofiltration, performed in experienced tertiary centers. 
  • VS-01 aims to provide a rapid ammonia clearance for all patients, and potentially alleviate the need for hemodialysis in acute hyperammonemia. 
The Urea Cycle

1. Brusilow SW et al., Adv. Pediatr. 43 (1996) 127-70.
2. Summar ML et al., Mol Genet Metab. 110 (2013) 179-80.
3. Hediger N et al., J Inherit Metab Dis. 41 (2018) 689-98. 

Decompensated Cirrhosis

Cirrhosis represents the end stage of every chronic liver disease and is one of the top leading causes of death worldwide (11th).Cirrhosis is a significant and growing global healthcare burden.2 The most common causes are chronic hepatitis, alcohol-related liver disease, and fatty liver disease, the latter becoming the dominant driver for decompensation (3-fold increase over the past 25 years), ACLF, and liver transplantation.3

Cirrhosis is characterized by an asymptomatic compensated phase followed by a decompensated phase, marked by the development of complications such as ascites and hepatic encephalopathy.4 Although compensated cirrhosis is often undiagnosed due to the lack of symptoms, patients are at constant risk of progressing to decompensated cirrhosis. Decompensated cirrhosis is a systemic disease primarily affecting brain, kidneys, and liver.5 If not treated adequately, it can have a significant impact on a patients’ life expectancy, dropping it to about 2-3 years once first decompensation occurs.4,5

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  • Globally, 123 million people suffered from cirrhosis in 2017. Over 10% had a decompensated cirrhosis, representing 1.6 million decompensated cirrhosis patients in USA and Western Europe alone.2
  • Each year, over 1.3 million people die from cirrhosis. Mortality has increased by 50% since 1990.2
  • About one third of patients with decompensated cirrhosis develop ACLF.6
  • The annual hospitalization cost burden for cirrhosis in the USA is above $12 billion and is mainly driven by the decompensated form.7,8

1. Asrani SK et al., J Hepatol 70 (2019)
2. Global Burden Disease Group, The Lancet 5 (2020) 245-66
3. Zhai M et al., Sci Rep 11 (2021) 5195
4. EASL, J Hepatol. 69 (2018) 406-60.
5. D’Amico G et al. J Hepatol 44 (2006) 217-31.
6. Mezzano G, et al. Gut (2021) 1–8.
7. Allen MA et al., Hepatology 64 (2016) 2165-72
8. Hirode G et al., JAMA 3 (2020) e201997

Hepatic Encephalopathy (HE)

HE is a serious neurologic condition caused when toxins, including ammonia, that are normally cleared by the liver accumulate in the blood, eventually affecting the brain. Elevated ammonia concentration in the serum and central nervous system (hyperammonemia) is the mainstay for the pathogenesis and treatment of HE. Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver failure, affecting between 30 and 40% of cirrhotic patients.1,2 Standard of care is limited and often unable to prevent further deterioration to ACLF.

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Ammonia Homeostasis

1.  Wijdicks EFM, New Engl J Med. 375 (2016) 1660-70.
2.  Vilstrup H et al., Hepatology 60 (2014) 715-35