During the first-quarter earnings call earlier this month, co-Chairman and CEO Terry Winters said Vital Therapies Inc. was "very close to enrolling the first patients" in the VTL-308 study testing cell-based therapy ELAD in severe acute alcoholic hepatitis, a statement that proved true Monday with the announcement that the first subject was recruited in the pivotal trial designed to redeem the liver-assist device following last year's failure in a broader range of liver failure patients.

At the time, the prospect of positive subset data did little to stop the free fall after the first phase III experiment in alcohol-induced liver decompensation, VTI-208, failed to show any appreciable difference in overall survival between the treatment and control groups. Vital Therapies' stock (NASDAQ:VTL) plummeted nearly 80 percent and traded as low as $2.81 in the days after the data were unveiled in August. (See BioWorld Today, Aug. 25, 2015.)

Shares slowly began regaining ground, however, as additional data became available. Vital Therapies reported in November post-hoc subset data, using Model of End-Stage Liver Disease (MELD) scores, which showed that those with higher MELD scores – in particular, patients with acute kidney failure or severe blood coagulation problems – had reduced tolerability to ELAD, likely contributing to the failure of VTI-208. Alternatively, patients without kidney dysfunction or severe coagulopathy treated with ELAD appeared to show promising trends toward efficacy.

Based on those findings, the San Diego-based firm designed the VTL-308 study, incorporating written feedback from the FDA, with a more clearly defined patient population. Specifically, VTL-308 will exclude patients age 50 and older and those who have MELD scores of 30 or higher. Also excluded will be patients whose creatinine levels are 1.3 mg/dL or above (limiting kidney dysfunction) or whose international normalized ratio is above 2.5 (limiting blood coagulopathy). Patients also must have a bilirubin level of at least 16 mg/dL.

Had those criteria comprised a pre-specified subset in the VTI-208 study, data from the 60 patients who matched those criteria would have shown a clear survival benefit at 180 days – 89 percent for the ELAD group vs. 48 percent for those receiving standard of care – with a "p" value of 0.01, the company said.

The new phase III will enroll about 150 subjects at about 40 sites in the U.S., U.K., Ireland, Germany and Spain – a total of 10 sites were open for enrollment as of Monday – and will measure overall survival through at least 91 days, using the Kaplan Meier statistical method, as the primary endpoint. As per the FDA, the company also added an event-driven design, which will continue enrollment until the full 150-patient target is hit and 55 events have occurred.

Top-line data are expected in mid-2018.

Vital Therapies likely will have to raise additional money before then, though. Cost-cutting measures implemented last fall, including a 30 percent work force reduction and the suspension of ongoing trials of ELAD in hepatic failure and severe acute alcoholic hepatitis, helped. As of March 31, the company had about $77.9 million on its balance sheet – another $6.6 million came from an at-the-market financing in April – with those funds expected to carry the company into the first quarter of 2018.

Shares of Vital Therapies (NASDAQ:VTL) closed Monday at $8.16, down 4 cents.

DRUG-DEVICE APPROACH

The ELAD, or extracorporeal liver-assist device, system is designed to work outside the body as a bedside unit to treat acute liver failure – either stabilizing a patient's liver until transplant or helping it regain a healthy state. The process starts with the patient's blood drawn from a central venous line and passed into an ancillary delivery system that isolates the plasma ultrafiltrate, which is then passed into four hollow fiber cartridges containing VTL C3A cells.

It's the incorporation of the VTL C3A cells that acts as the secret sauce for ELAD. Derived from the firm's cell bank, the immortal VTL C3A cells have shown the ability to mimic some functions of human liver cells, including an active P450 enzyme system and the production of liver-specific proteins albumin, alpha-fetoprotein, C3 complement, factor V, alpha-1 antitrypsin, growth factors , immunomodulatory proteins and others.

Once treated through the ELAD system, plasma ultrafiltrate is filtered, reconstituted with blood cells and returned to the patient. A single session of continuous treatment is expected to last between three days and 10 days.

ELAD has orphan designation in the U.S. and Europe for acute liver failure, for which surgical transplantation is the only long-term treatment option. But for many patients, that never happens; Vital Therapies quotes estimates from the United Network for Organ Sharing showing that fewer than 6,500 liver transplants were performed in the U.S. in 2013, due to a lack of available donor organs. About 1,500 patients die each year while awaiting a transplant.

ELAD was acquired by Vital Therapies during Vitagen Inc.'s 2003 bankruptcy proceedings, and the firm is planning a solo trip to market.

"Assuming successful clinical results in the future, we plan to seek regulatory approval and to commercialize ELAD directly in most major markets in the world," Winters told investors during the first quarter call.