Reata and Abbott Halt Phase 3 BEACON Trial For Bardoxolone Methyl Amid Serious Safety Concerns
On October 18, Reata and Abbott stopped their phase 3, 2,000-patient BEACON trial for the drug bardoxolone methyl, the most promising candidate in development for the treatment of chronic kidney disease (CKD). The trial was terminated due to an excessive number of serious adverse effects, including death, among those taking bardoxolone in the study. This is shocking and deeply disappointing news, particularly because the earlier phase 2 results for bardoxolone had been so encouraging – the drug showed the potential to both ease the symptoms of CKD and to actually reverse it through anti-inflammatory mechanisms.
The stakes were very high for bardoxolone since nothing of its kind is currently available, and it would have offered a sorely needed treatment for a very ill group of patients. As context for how grave a condition stage 4 CKD is (the disease state being tested in this trial), a 2004 study found that the five-year mortality rate of patients with stage 4 CKD was 46% – worse than many cancers. The companies have not released further information about why these safety problems arose, the magnitude of the problems, or the next steps with the drug. While it is possible that bardoxolone is simply not safe for use as a CKD treatment, these adverse events may be the result of unfortunate statistical variance or perhaps due to flaws in the study design. In particular, BEACON focused on patients with type 2 diabetes and stage 4 CKD, the most advanced stage of CKD before dialysis is needed. As a result, it’s possible that the participants were too ill to handle the treatment. Given that no glaring safety signals were apparent in the smaller phase 2 study (BEAM) with stage 3 and 4 CKD patients (though we note this was a much smaller study of 227 patients), we wonder if Reata and Abbott will still attempt to develop the drug for less severe forms of CKD. In any case, we will continue to monitor this story for more information on what went wrong in the BEACON trial. –AW/AB