UPDATE 2-Cumberland says FDA rejects liver drug's new indication

Wed Dec 22, 2010 11:33am EST

By Rajarshi Basu
BANGALORE, Dec 22 (Reuters) - Cumberland Pharmaceuticals Inc (CPIX.O) said U.S. health regulators did not approve the use of its liver drug for an additional indication, sending its shares down as much as 16 percent.

The drug, Acetadote, is currently approved to treat liver failure caused by an overdose of acetaminophen, a common ingredient in painkillers.

The FDA rejection raises the possibility that the drug's exclusivity may not get extended, Jefferies & Co analyst David Windley told Reuters.

Acetadote's orphan status will get over in January, which means threat from competitors is near.
In March the company had filed a supplementary new drug application for an indication of the drug to treat liver failure caused by factors such as hepatitis B and autoimmune hepatitis.
The Food and Drug Administration said the indication did not offer sufficient evidence of efficacy in increasing survival in all patients with acute liver failure.

Analyst Michael Tong of Wells Fargo Securities said in a note that the new indication could have added $30-$40 million to Acetadote's sales over the next 3-5 years.
Cumberland had annual sales of $43.5 million last year.

In October, Cumberland also submitted an application to the FDA for approval of a new, second generation formulation of Acetadote to replace the current product.

Analyst Windley said the company expects to get exclusivity on the new formulation.
Cumberland, whose products include Caldolor injection to treat fever and pain and laxative Kristalose, reported quarterly revenue of $12.2 million in its third quarter.
Shares of Nashville, Tennessee-based Cumberland have gained 5 percent since August when the FDA extended the review date for the drug's new indication by three months.
They were down 7 percent at $6.39 in late morning trade on Wednesday on Nasdaq in heavy trading. They touched a low of $5.79 earlier in the session. (Reporting by Rajarshi Basu in Bangalore; Editing by Don Sebastian, Unnikrishnan Nair)
http://www.reuters.com/article/idUSSGE6BL08320101222?feedType=RSS&feedName=rbssHealthcareNews

AASLD/ELAD® Bioartificial Liver/3yr Follow Up Confirm Saftey&Survival Benefit

Three-Year Follow-Up Data Confirm Safety and Survival Benefit in Chinese Liver Failure Patients Treated With ELAD® Bioartificial Liver

Poster presentation scheduled at AASLD November 2nd

Vital Therapies, Inc.

/PRNewswire/ -- Vital Therapies, Inc., (VTI) today announced that a poster is being presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston on Tuesday, November 2nd. It confirms that previously reported findings of improved transplant free survival (TFS) in Chinese subjects with acute-on-chronic liver failure (ACLF) treated with the ELAD® bioartificial liver support system are maintained for up to three years.

The poster is titled "3-year follow-up of acute-on-chronic liver failure (ACLF) subjects in randomized, controlled, multicenter trial of ELAD® bioartificial liver support system in 49 Chinese subjects reveals significant transplant-free survival (TFS) benefit." It is being presented by Dr. Michael Millis, Professor of Surgery, University of Chicago, and is coauthored by Drs. Zhongping Duan and Jing Zhang, Beijing You'an Hospital, and Shaojie Xin and Shaoli You, 302 Military Hospital, Beijing.

Previously, it was reported that 84-day follow-up of ACLF subjects enrolled at two liver treatment centers in China showed statistically significant improvements in TFS for ELAD treatment compared with standard of care (SOC). At least three years following enrollment, survivors were consented and underwent a cancer screen and physical exam in accord with a questionnaire.

Of 49 subjects enrolled, 84-day TFS was 21/32 (65.6%) in the ELAD group vs. 7/17 (41.1%) in controls. Three-year TFS was 14/32 (43.8%) in the ELAD group vs. 3/12 (25%) in controls. Of 84-day survivors, 2/21 (9.5%) ELAD and 2/7 (28.6%) controls died, 1/21 (4.8%) ELAD and 0/7 controls were transplanted and 4/21 (19.0%) ELAD and 2/7 (28.6%) controls were lost to follow-up. Survival analysis reveals a statistically significant improvement in TFS (p=0.045, log-rank analysis) for the ELAD treated subjects compared with SOC. Median survival of controls was 37 days, whereas median survival of ELAD treated subjects was at least 3 years. There was no evidence of tumor development in either group.

Dr. Millis commented, "This is the first time that a long term survival benefit has been demonstrated in subjects who recovered following treatment with ELAD. It is highly encouraging to note that those subjects that survive in the short term are able to go on to extended survival without any apparent increase in mortality or morbidity compared with subjects administered standard of care."

Dr. Duan, who served as a principal investigator for the study, commented, "China has about 95 million HBV carriers and chronic hepatitis B patients, and 38 million hepatitis C patients. It is estimated that 0.1%-0.5% of these patients will experience severe hepatitis due to acute hepatocellular necrosis or hypofunction, which results in hepatic insufficiency and hepatic failure. Mortality from this condition still remains around 50%-70% even with comprehensive internal medicine treatment, leading to as many as 400,000 deaths per year in China from acute liver failure. When approved for commercial sale in China, ELAD will be the first bioartificial liver support system proven to improve survival in this population."

In order to confirm these findings from China, VTI is conducting the SILVER (Stabilization In LiVER Failure) trial in the United States, Europe and Saudi Arabia which has achieved 50% of its targeted enrollment. Should this study yield positive findings, these results, along with data from other studies, will form the basis of regulatory filings for future marketing authorization.

About ELAD and the SILVER Trial

The SILVER protocol enrolls subjects with chronic liver disease who have been hospitalized as a result of an event, such as an infection or an episode of bleeding, which has caused deterioration of their liver function (acute-on-chronic liver failure, ACLF). The trial is designed to explore whether the use of ELAD in this setting can prevent continued deterioration of liver function, called progression, and thus improve survival. The trial design uses a well-established measure of liver function called the MELD score to define the status of liver function. Treatment with ELAD, along with standard of care, is compared with standard of care alone. The time to either death or deterioration of liver function by a pre-specified amount is measured. It is postulated that the use of ELAD may extend the time to progression and improve survival in this rapidly progressing patient population.

ELAD is a biologic liver support system using a proprietary line of allogeneic human liver cells refined by several leading cell experts. The cells are stable, immortal, can be grown in unlimited quantities and retain their hepatocyte (liver cell) characteristics. About one pound of cells is used for each treatment. The cells are grown in specially designed cartridges at VTI's cell culture facility and used to treat the patient for up to ten days.

About Vital Therapies, Inc.

Vital Therapies, Inc. (VTI) is based in San Diego, California, with a wholly owned subsidiary in Beijing, China. VTI is developing the first human liver cell-based Extracorporeal Liver Assist System (ELAD). ELAD could provide support for patients with severe liver failure by processing toxins and also synthesizing proteins and metabolites that are key products of normal human liver function. ELAD is in investigational clinical trials and VTI completed a pivotal trial and filed for market approval in China in September 2007. For additional information visit http://www.vitaltherapies.com/ or contact Terry Winters, PhD, CEO, Vital Therapies at +1 858 673 6840.

ELAD is a trademark of Vital Therapies, Inc.

SOURCE Vital Therapies, Inc.
http://www.kansascity.com/2010/10/13/2311093/three-year-follow-up-data-confirm.html