ENDO trial of EndoBarrier Therapy in obesity and type 2 diabetes fails to meet endpoint- GI Dynamics

GI Dynamics has received the initial top-line results from its U.S. pivotal clinical trial of EndoBarrier Therapy for glycemic improvement in inadequately controlled, obese, type 2 diabetic subjects on oral anti-diabetic agents (the ENDO Trial). In July 2015, the Company terminated the ENDO Trial early due to seven cases of hepatic abscess, a bacterial infection of the liver, a number of cases that was greater than expected. Because of the early termination, only 325 of the planned 500 subjects were randomized into the trial.

Based on the initial analysis of the final dataset, the ENDO Trial demonstrated efficacy of EndoBarrier Therapy for the treatment of type 2 diabetes with an average reduction of hemoglobin A1c (HbA1c) from baseline to 12 months that was 0.71% greater with the device than with sham intervention. The effectiveness of EndoBarrier Therapy, however, did not meet the protocol-specified Primary Efficacy Endpoint criterion, a statistical test that demonstrates a greater than 96.5% probability that the change in HbA1c was at least 0.4% greater with EndoBarrier Therapy than with sham control. The pre-specified probability criterion was 96.5%, compared with the result of 92.8%. These results are nonetheless encouraging, given that (1) the trial only enrolled two-thirds of the intended subjects; and (2) because of early suspension of the trial, data for nearly one-third of the enrolled and randomized subjects were not available for the protocol-specified primary efficacy analysis.

EndoBarrier Therapy did not meet the protocol-specified Primary Safety Endpoint, defined by device-related serious adverse events (SAEs) requiring early device removal as adjudicated by an independent Clinical Events Committee. Device-related SAEs requiring removal occurred in 11.7% of subjects. This safety failure was largely due to the excess number of hepatic abscess that occurred in subjects implanted with the device. The Company plans to submit the final report of the ENDO Trial to the FDA in April 2016, and anticipates peer-reviewed publications and presentations at scientific conferences to provide the public with a more detailed analysis of the trial data.

Comment: The EndoBarrier received CE Mark approval for Europe in 2010, as well as approval by the Therapeutic Goods Administration in Australia in 2011 for the treatment of type 2 diabetes and/or obesity.