Announced by Reata Pharmaceuticals on February 25, the Complete Response Letter from the FDA for bardoxolone methyl comes a little over 2 months after an FDA advisory committee voted unanimously against approval of the once-daily, orally administered activator of Nrf2.
The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Reata Pharmaceuticals, Inc. for their chronic kidney disease (CKD) treatment bardoxolone methyl, according to a February 25 statement from the company.
The subject of a December 8, 2021, Cardiovascular and Renal Drugs Advisory Committee meeting where committee members voted unanimously against approval, Reata Pharmaceuticals stated the FDA concluded it did not believe the submitted data demonstrated bardoxolone’s ability to slow the loss of kidney function in patients with Alport syndrome and reducing the risk of progression to kidney failure. The statement from Reata Pharmaceuticals also additional data from the company to support the efficacy and safety of bardoxolone.
“This outcome is a significant disappointment for our company, as well as the many patients, families, and investigators who have participated in our development program for bardoxolone in Alport syndrome patients. We will continue to work with the FDA to confirm our next steps on our Alport syndrome program,” said Warren Huff, Reata’s Chief Executive Officer.
A disease with no approved therapies, Reata submitted their New Drug Application for bardoxolone in the treatment of chronic kidney disease caused by Alport syndrome in April 2021. The NDA for the company was supported by data from the phase 3 CARDINAL trial. The FDA had notified Reata Pharmaceuticals at the time of submission they were planning an advisory committee meeting to discuss the application.
That meeting, which was held on December 8, included a vote where all 13 members of the committee voted unanimously the provided evidence did not indicate bardoxolone was effective in slowing the progression of chronic kidney disease in Alport syndrome and that its benefits outweigh its risks. Committee members cited low enrollment of patients from the adolescent population, questionable efficacy, and concerns with the safety profile in the CARDINAL or BEACON trials as the rationale behind their decision-making.
In their release, Reata pointed out bardoxolone is currently being studied in EAGLE, an open-label, extended access trial in patients with chronic kidney disease caused by Alport syndrome who participated in the CARDINAL trial and patients with autosomal dominant polycystic kidney disease who participated in the FALCON trial, and AYAME, a Phase 3 study for the treatment of diabetic kidney disease being conducted in Japan.