Liver Failure

August 31, 2015

Vital Therapies has issued results of a phase III study of VTI-208 for alcohol-induced liver decompensation (AILD). The randomized, controlled, open-label trial failed to meet the primary endpoint of overall survival through at least 91 days assessed using the Kaplan Meier statistical method. Of 203 total subjects enrolled in VTI-208, 96 were randomized to the treated group and 107 were randomized to the control group. A hazard ratio of 1.027 (slightly favoring the control group) with a log rank p=0.90 (not statistically significant, N.S.) indicated that there was no difference between treated and control subjects in the primary endpoint. The secondary endpoints of proportion of survivors at study days 28 and 91 also showed no difference between the groups (Pearson’s Chi-squared p=0.45 [N.S.] and 0.74 [N.S.], respectively). The company will be analyzing the data from the VTI-208 clinical trial during the next several weeks, including data from the pre-specified subset analyses. The company will stop the VTI-210 and VTI-212 clinical trials, and also plans to meet with the FDA as soon as possible to discuss restructuring its clinical development program, including a potential new trial to confirm the information suggested by the subset analyses. The company is encouraged that a large pre-specified subset of 120 subjects with a MELD score of less than 28 had a hazard ratio of 0.575 and a log-rank p=0.077 (N.S.) in favor of the ELAD group, suggesting future clinical studies should focus on that cohort with MELD scores less than 28. Separately, a pre-specified subset of 101 subjects under age 46.9 years (the study median age) had a hazard ratio of 0.634 with a log-rank p=0.167 (N.S.) in favor of the ELAD treated subjects, suggesting that future study designs may incorporate stratification by age. Those effects do appear to be additive and a subset of 59 subjects with MELD less than 28 and age less than 46.9 years had a hazard ratio of 0.375 in favor of the ELAD group (p=0.085 [N.S.]).