Medical Device Daily
Vital Therapies (VTI; San Diego), a company attempting to bring to market what would be the first “bioartificial” liver, on Thursday reported that it has completed the interim analysis of the first 45 patients enrolled in its pivotal trial of its ELAD (Extracorporeal Liver Assist Device) System in China.
Thus far, much good news.
The trial, which is studying the liver assist device in patients with chronic liver disease, indicates statistical significance with the endpoint of transplant-free survival. The trial is being conducted at Beijing Youan and 302 Military Hospital in Beijing.
“Obviously, No. 1, it increases our confidence that we’ve got a safe and effective product,” Terry Winters, CEO and chairman of VTI, told Medical Device Daily.
Winters said the company will have to submit the results of its trial in China to the FDA once it requests permission to begin a Phase III trial in the U.S. later this year.
“We would certainly hope that FDA would look favorably” on the China study “for purposes of safety and possibly for efficacy,” he added.
ELAD is designed to augment the metabolic functions of a patient’s liver, thereby enabling a bridge to transplant or recovery. The company bills it as a “biologic” device that is similar to renal dialysis in patients suffering from kidney failure, Winters said.
The system consists of four cartridges containing cells, called the human hepatocyte cell line, or C3A, that functions like a normal human liver by metabolizing toxins and removing waste products while delivering essential proteins back into the plasma. Those cartridges are incorporated in a blood pumping system at the patient’s bedside in the hospital. Continuous patient treatment is possible for up to 12 days.
The company said the system differs from the mechanical filtration systems in development, as VTI’s system uses an immortalized line of human liver cells which, in addition to processing and removing blood toxins, can also supply to the patient metabolites synthesized by the liver, such as blood-clotting proteins.
Of the 42 patients thus far considered evaluable, the statistics showed that the endpoint of transplant-free survival has already achieved statistical significance. Hepatitis, a primary cause of liver failure, is considered endemic in China.
“We have been very pleased with the clinical response we have seen in patients suffering from acute exacerbation of chronic liver disease,” said Duan Zhong-Ping, MD, lead investigator and professor of Beijing Artificial Liver Treatment & Training Center and vice president, Beijing Youan Hospital. “Our center has treated a large number of patients with other mechanical and bioartificial liver treatments, and although the data with ELAD is preliminary, none has looked more promising than ELAD to impact a patient’s long-term survival from a single treatment.”
The best explanation for this, Zhong-Ping suggested, is that ELAD actually regenerates the liver, because the improvement in the liver continues after the treatment ends.
And while the study continues, Zhong-Ping said he expects the p values to change as more data is generated. He added: “It is encouraging to be achieving these kinds of values halfway through the trial.”
VTI said that “consistent with the recoveries” that physicians have seen in patients participating in the trial, “other measures indicate the success of the trial to date.”
Among those measures is the fact that eight of 14 patients (57%) in the control group have either died or had to be transplanted, compared to seven of 28 (25%) in the group treated with the ELAD.
Biochemistry measures such as bilirubin and albumin, as well as observations such as appetite and fatigue are also showing “expected improvements” in treated patients.
“We were expecting good results, but we are surprised on the upside, and we are just delighted to see patients recovering so well,” Winters told MDD.
Winters also noted the “flawless” scale-up of manufacturing and the logistics of providing ELAD cartridges to China.
“This has given us the confidence to be able to provide commercial quantities of ELAD cartridges to China from our plant in San Diego starting with the planned market launch [in China] in late 2007,” Winters said.
To support the beginning of U.S. Phase III trials late this year as well as the Chinese product launch, the company said it is seeking a Series C private equity financing in the U.S. and China. The company has already reported positive results from earlier Phase I and II trials in the U.S.
The market opportunity for such a bioartificial liver, if successful, is significant, with the World Health Organization (WHO; Geneva) estimating that severe liver diseases affect about 12 million people worldwide. In China, more than 140 million are infected with a hepatitis virus, and 32 million have active viral liver disease.
VTI in 2003 acquired the assets of VitaGen (La Jolla, California) to continue the development of ELAD (Medical Device Daily, Oct. 2, 2003). The essential technology of the ELAD system, its human hepatocyte cell line, C3A, can be grown, stored and shipped worldwide, and the company has an endless supply.
The C3A cell line was originally licensed from the Wistar Institute (Philadelphia) and further developed by Baylor College of Medicine (Houston), VTI said.
But VTI has competition to develop a bioartificial liver in the U.S. from Arbios Systems (Los Angeles/Waltham, Massachusetts), which reported in November results on the first patients in a clinical trial to assess tolerability and indications of clinical utility of its SEPET liver-assist device (MDD, Nov. 2, 2006).