- Kyowa Hakko Kirin will begin a new phase 2 clinical trial of bardoxolone methyl, “with a particular emphasis on patient safety.”
- Reata’s phase 3 BEACON trial for this drug was terminated in 2012 due to an excess of serious cardiovascular events.
Japan-based pharmaceutical company Kyowa Hakko Kirin announced today that it will begin a new phase 2 clinical trial of bardoxolone methyl, Reata’s potentially game-changing compound for patients with type 2 diabetes and advanced chronic kidney disease (CKD). As a reminder, Reata had its phase 3 BEACON trial terminated in 2012 due to an excess of serious cardiovascular events. We had (what we had thought might be naïve) hopes that the drug might be revived, since some had suggested that the excess in CV events in the phase 3 trial had in part been caused by enrolling patients that were already too sick (stage 4 CKD). A detailed analysis of the BEACON study presented at this year’s European Renal Association-European Dialysis and Transplant Association Congress suggested that a subset of patients with certain baseline risk factors – more advanced renal dysfunction, high fluid retention, and a prior history of cardiovascular disease – were responsible for the increased rate of adverse events in the bardoxolone methyl arm, and that when those patients were excluded, the rate was comparable to the placebo group. In light of this analysis, Kyowa Hakko Kirin has decided to continue the development of bardoxolone methyl for patients with type 2 diabetes and CKD “with a particular emphasis on patient safety.” Kyowa Hakko Kirin licensed the drug from Reata Pharmaceuticals and has exclusive rights to develop and commercialize bardoxolone methyl in Japan, China, Taiwan, Korea, and Southeast Asia. The company had suspended its own phase 2 trial in November 2013 in response to the safety concerns and has now decided to pursue this new development strategy. For its part, Reata is now conducting a phase 2 study of the compound for patients with pulmonary arterial hypertension but is not currently pursuing it as a treatment for CKD.
We look forward to hearing more details about the design of this new trial (it was not listed on ClinicalTrials.gov at the time of publication), and we hope that with greater attention to potential cardiovascular risk, bardoxolone methyl could still be a viable candidate for the treatment of CKD in some patients. There are currently very few effective treatment options for this devastating disease, and bardoxolone’s unique anti-inflammatory mechanism could potentially make it a paradigm-shifting therapy. As a reminder, results from the phase 2 BEAM trial seemed especially promising because gains in eGFR for the mid- and high-level doses tested persisted for the entire 52 weeks of treatment and even after treatment discontinuation, suggesting that the drug was disease-modifying and could reverse CKD (which no other drug can currently do). The rate of CKD in patients with type 2 diabetes is on the rise – the CDC estimates that the number of patients on dialysis or with a kidney transplant due to diabetes rose 13% from 2008 to 2011 – and further development in this arena in terms of disease-modifying drugs is sorely needed.
-- by Emily Regier, Jessica Dong, and Kelly Close