Vital Therapies, Inc. is a biotherapeutic company that has been developing a cell-based therapy targeting the treatment of acute forms of liver failure. The Company’s ELAD® System, an extracorporeal human allogeneic cellular liver therapy, recently reported top-line data from its phase 3 clinical trial in severe alcoholic hepatitis. Although there was a numerical improvement in survival in the ELAD-treated group between three months and one year following randomization, the study failed to meet the primary endpoint of a significant improvement in overall survival through at least ninety-one days assessed using the Kaplan Meier statistical method. The secondary endpoint of the proportion of survivors at study day ninety-one also showed no statistically significant difference between the groups.
In light of these results, the Company does not believe the ELAD System can be approved in the United States or European Union, if ever, without additional clinical trials that would require substantial capital and time to complete. Consequently, the Company has ceased any further development of the ELAD System and is exploring strategic options.
Severe Alcoholic Hepatitis (sAH)
Severe alcoholic hepatitis (sAH) is a deadly liver disease that occurs following a spike in alcohol consumption, increasing the risk of liver failure and death. As therapeutic options are limited, Vital Therapies is committed to developing a potentially life-saving treatment option for this underserved patient population.
- Severe alcoholic hepatitis (sAH) is a type of acute liver decompensation that is directly related to excessive consumption of alcohol. sAH is characterized by inflammation and enlargement of the liver.
- An estimated 30,000 people in the U.S. each year suffer from a particularly debilitating form of sAH that is associated with significant mortality and a hospital stay of at least three days.1
- Treatment options for patients with sAH are limited.2 The current standard of care includes corticosteroids, n-acetyl cysteine with corticosteroids, and pentoxifylline, but none have been shown to significantly affect long-term survival. While patients with sAH can appear stable and even dischargeable from the hospital, their prognosis following treatment with standard of care is grim. Mortality at 90 days is approximately 40 percent.3
The Department of Health and Human Services in the U.S. estimates that for 2014 the number of hospital admissions related to sAH in the U.S. was approximately 102,000, with approximately 15,000 of these admissions identifying sAH as the primary diagnosis. In addition, approximately 323,000 hospital admissions occurred in 2014 related to alcoholic cirrhosis, alcohol liver damage not-otherwise-specified or alcoholic fatty liver, with approximately 50,000 hospital admissions identifying these conditions as the primary diagnosis.
In addition to treating patients with sAH, we believe that a subset of liver disease patients with non-sAH may be treatable with the ELAD System. Incidence rates for both sAH and non-sAH liver disease appear to be similar in Europe.
related to sAH in the U.S. in 2014
sAH is costly to treat. The average annual treatment cost per patient is higher than that for heart failure and diabetes. This cost does not take into account the additional economic impact of sAH related to reduced productivity and lost income.1
The liver performs a wide variety of vital functions including metabolic, regulatory, detoxification, and synthetic activities. The primary liver cell, the hepatocyte, is believed to be responsible for approximately 500 or more specific biologic processes. In addition, the liver serves as a reservoir for immune cells that clear the blood of pathogens. Consequently, the liver’s failure to perform its normal role can have devastating or fatal consequences. Causes of liver failure are numerous, and the condition is typically described in terms of rapidity of onset.
Each year 80,000 people in the U.S. and Europe suffer from acute forms of liver failure, which can result in a mortality rate of up to 50 percent.
Acute Liver Failure
Acute Liver Failure (ALF) is a relatively rare condition in which liver function rapidly deteriorates in an individual without a known pre-existing liver disease. The patient experiences an altered mental state and blood clotting deficiencies. The most frequent causes of ALF are drug or toxin-induced liver injury, viral hepatitis and autoimmune disease. In the U.S., an estimated 2,000 cases of ALF occur each year. The current standard of care is liver transplantation. Patients with ALF receive priority on the liver transplant list, although they tend to progress very rapidly and may succumb to their disease before a suitable organ becomes available.
Chronic Liver Failure
Chronic liver failure is characterized by the presence of widespread cirrhosis, or the replacement of normal liver tissue by fibrosis, scar tissue, and regenerative nodules. As normal liver tissue is destroyed, the organ gradually fails to perform its normal functions. Damage from cirrhosis cannot be reversed, and lost liver function can be regained only through transplantation.
Acute-on-Chronic Liver Failure
Hepatocellular damage, secondary to a variety of insults (e.g. infectious agents, alcohol, exogenous drugs, autoimmunity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis), can result in chronic liver disease, if the underlying etiology is not effectively treated. This condition is characterized histopathologically by increasing degrees of fibrosis and cirrhosis, and frequently remains subclinical or undiagnosed. Often as a result of a secondary insult, the liver can decompensate, leading to a life-threatening disorder known as acute-on-chronic liver failure or ACLF.
Post-Surgical Liver Failure
Another acute form of liver failure also can occur following a surgical procedure due to:
- Primary graft non-function, which occurs when a newly transplanted liver fails to function. This is a life-threatening medical emergency, and can lead to death if a new organ does not become available quickly.
- Small-for-size or split liver transplant, which occurs when the transplanted liver is functioning but is too small to sustain the patient. This occurs because only a small donor liver was available or a live person donated a portion of their liver for transplantation.
- Liver cancer resection. Primary liver cancer can sometimes be cured by resecting the cancerous part of the liver after which the remaining liver regenerates to full size. Currently, surgeons typically resect only up to 50 percent of the liver in order to avoid death from liver failure. However, more extensive resections occasionally occur, and resection of smaller portions can also lead to liver failure.
Limitations of Currently Available Treatments
for Acute Forms of Liver Failure
Given the liver’s complexity, there are no simple or widely effective medical solutions for acute forms of liver failure. The only long-term cure for acute forms of liver failure is surgical transplantation. According to the U.S Department of Health and Human Services’ Organ Procurement and Transplantation Network, 8,082 liver transplants were performed in the U.S. in 2017. Approximately 14,000 patients are currently on the transplant waiting list in the U.S. and approximately 1,200 patients die each year while waiting. In Europe, approximately 7,000 liver transplants are performed each year. The average billable charge for a liver transplant in 2017 was $812,500.4
- Thompson JA, Martinson N, Martinson M. Mortality and costs associated with alcoholic hepatitis: a claims analysis of a commercially insured population. Alcohol. 2018. https://doi.org/10.1016/j.alcohol.2018.02.003
- Mayo Clinic MELD Score and 90-Day Mortality Rate for Alcoholic Hepatitis.
- Millman Research Report, 2017 U.S. organ and tissue transplant cost estimates and discussion, August 2017