Sometimes when something appears too good to be true, it is too good to be true. Last year, a paper was published in the NEJM reporting a preliminary study of bardoxolone for the treatment of diabetic nephropathy. At the time, this seemed like it might be promising but there were a number of issues with the study including the use of eGFR as an endpoint and the fact that the use of the drug was associated with a significant rise in albuminuria, both of which we raised here in a blog post . More recently, we posted again on this drug. An experiment in monkeys revealed that bardoxolone downregulated the expression of megalin in the proximal tubule and that this may have been responsible for the increase in albuminuria.
All this time, a phase 3 study was ongoing to determine what the true effect of the drug was in a larger group of patients. Unfortunately, it was announced last week that the trial had been stopped. According to an article in marketwatch, there were "excess serious adverse events and mortality in the bardoxolone methyl arm" according to the monitoring committee. We don't know yet what exactly happened and the company is not releasing any more data beyond this simple statement. I am sure more information will come out in the future.
This is extremely disappointing. For all that it seemed too good to be true, there are so few things that we have in our toolbox to delay the progression of diabetic kidney disease that this was potentially a blockbuster treatment for this condition. There may be aspects of this drug that remain useful in some specific circumstances and it may also aid in future drug development. We will not know the answers to these questions until the final study results are published.