Shares of Reata Pharmaceuticals have plunged nearly 40% in premarket trading after an FDA advisory panel recommended against the approval of its Alport syndrome disease treatment, bardoxolone.
Shares of Reata Pharmaceuticals have plunged nearly 40% in premarket trading after the company’s announcement late Wednesday that an FDA advisory panel unanimously recommended against its Alport syndrome disease treatment, bardoxolone.
The Cardiovascular and Renal Drugs Advisory Committee gave bardoxolone a thumbs down on whether or not the clinical evidence demonstrated that the experimental drug effectively slows down the progression of chronic kidney disease (CKD) in patients with Alport syndrome and that its benefits outweigh its risks. The committee vote was 13-0.
The AdComm rejection is not surprising given the release of an FDA staff document that questioned the efficacy of bardoxolone, a once-per-day activator of Nrf2, a transcription factor that induces molecular pathways involved in resolving inflammation. The FDA staff documents concerns about the clinical data submitted to support the potential approval of bardoxolone. The regulatory agency scientists were concerned about the estimated glomerular filtration rate (eGFR), a key measure of kidney function, which was the primary endpoint of the Phase III CARDINAL study supporting the company’s New Drug Application.
The Phase III data showed that patients who received bardoxolone saw statistically significant improvement in mean-estimated eGFR. Additionally, the data from CARDINAL showed that after a four-week withdrawal period, the Alport Syndrome patients saw a statistically significant improvement compared to placebo in mean retained eGFR.
However, in the briefing documents, the FDA staff raised concerns about the data, saying despite Reata’s explanations, the “loss of statistical significance based on a change in a single factor in the analytic model raises concerns regarding the robustness of the study’s findings.” And that was expressed by the AdComm team as well.
The FDA has granted Bardoxolone Orphan Drug designation to treat Alport syndrome and autosomal dominant polycystic kidney disease, a genetic disease that causes the formation of cysts in the kidneys. Alport syndrome causes kidneys to progressively lose the ability to filter waste products from the blood.
The staff document was released several months after the company noted in its August quarterly report that the FDA identified a number of clinical and statistical issues in the study that needed to be addressed.
J. Warren Huff, president and chief executive officer of Reata Pharmaceuticals, noted his disappointment with the committee’s vote.
“We believe the scientific evidence supports bardoxolone approval in the U.S. for CKD in patients with Alport syndrome, which is one of the most rapidly progressive forms of CKD. We will continue to work with the FDA to answer any questions they may have,” Huff said in a brief statement.
The PDUFA date for bardoxolone is Feb. 25, 2022. The FDA is not required to follow the recommendation of its AdComm, but typically does.
In addition to seeking approval for bardoxolone in the United States, Reata has also filed for approval with the European Medicines Agency. Its partner, Kyowa Kirin, submitted an NDA to the Ministry of Health, Labour and Welfare in Japan.
