NCHR’s Testimony to FDA on Bardoxolone for Alport Syndrome

December 8, 2021


Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Meg Seymour, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest. 

You are being asked to assess whether bardoxolone can slow the progression to kidney failure in patients with Alport Syndrome (AS).

We agree with FDA scientists that although the sponsor met prespecified primary and secondary endpoints, the submitted data do NOT demonstrate that bardoxolone is effective at slowing the loss of kidney function and reducing the risk of progression to kidney failure. Those are the outcomes that matter most to patients. 

In addition to concerns about efficacy, we are concerned about its safety as well. There were so few patients evaluated for safety that data from an earlier trial on people with kidney disease due to diabetes were added to the analysis. However, those previous data were from a study that was terminated “for safety concerns due to excess serious adverse events and mortality.” 

Further, bardoxolone may affect blood pressure, potentially leading to cardiovascular risks, but the full extent of that risk is unknown because patients with heart problems were excluded from the study. We agree with FDA reviewers’ concerns that, over the long-term, the cardiovascular effects in addition to the effect of albuminuria could actually accelerate the progression to kidney disease. It is expected that bardoxolone would be taken long-term, and thus it is crucial to understand its long-term effects. 

Finally, we are concerned about the very small number of children studied. The sponsor is seeking approval for patients ages 12 years and older, but there were only 11 pediatric patients in the treatment arm. We agree with the FDA reviewers that this sample size is too small to draw conclusions about the effects of the drug on weight or how it might affect development. 

We agree that there is an urgent need for therapies for AS that can reduce the risk of progression to kidney failure. However, patients deserve drugs that have been proven to be safe and effective with meaningful outcomes. We urge you to consider the balance of potential benefits and risks for long-term use of the drug during your discussion and vote today.

 

The Advisory Committee unanimously voted against the approval of bardoxolone.