UPDATED: FDA adcomm votes unanimously against Reata's potential Alport syndrome treatment
The US FDA’s Cardiovascular and Renal Drugs Advisory Committee on Wednesday voted 13-0 that the agency should not approve Reata Pharmaceuticals’ bardoxolone methyl capsules as a treatment to slow the progression of chronic kidney disease in those with the rare Alport syndrome.
The lopsided vote follows similar comments from FDA on Monday, which painted an overwhelmingly negative opinion on Reata’s $RETA potential drug, according to briefing documents released ahead of today’s meeting.
Reata’s stock price fell by another 44% in after-hours trading, after a previous 30+% drop earlier in the week.
And adcomm members largely agreed with the agency Wednesday, saying safety concerns gave them serious pause, while taking issue with the way Reata ran its Phase III trial, and the complexity of the data presented. Members of the committee also sought clarifications on why Reata used eGFR as the main measure for its Phase III, noting other measures might have been more informative.
“FDA set the tone and the committee resoundingly agreed, discounting all of Reata’s arguments and leaving almost zero chance of approval,” Baird biotech analyst Brian Skorney wrote in a note to investors.
The use of eGFR, which is an estimate of the kidney’s filtration rate, was meant to assess disease progression, with Reata arguing that its Phase III showed patients treated with bardoxolone experienced a statistically significant improvement in kidney function as measured by eGFR at Week 100 and Week 104, compared to patients treated with placebo.
Nearly every adcomm member seemed to disagree with that conclusion.
Panelist Paul Palevsky, chief of the kidney medicine section at the VA Pittsburgh Healthcare System, said that as much as he wants to see a drug that has an alternative mechanism for improving function for this relatively rare form of kidney disease, he’s “quite concerned that the data provided does not meet the bar of showing this will slow the time to end stage kidney disease.”
Adcomm member Patrick Nachman, professor of medicine at the University of Minnesota, also expressed worries about the generalizability of the data presented, saying that the data did not show benefit, but that he’s sensitive to the idea there might be a group of patients that could benefit from this treatment.
In the summary after the first discussion question of the meeting, chair of the adcomm Julia Lewis, professor of medicine at Vanderbilt, raised several lingering questions too, like why only enroll 11 adolescents in the Phase III if the sponsor is seeking an indication for an age group of 12 and up?
Panelist Susan Mendley of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases also called on Reata to study the drug more in the younger population as she’s concerned on the effects of weight gain and growth outweighing the benefits.
Adcomm member Gregory Gorman, captain in the medical corps of the US Navy, said that as a pediatric nephrologist, he would’ve liked to hear that some patient-reported outcome measures were improving. Others questioned why the patients were unblinded to their GFR estimates, and how that could have biased how they perceived their outcomes.
“I might have given it the benefit of the doubt,” Gorman said, but that’s nullified by bardoxolone’s safety concerns, and even with the statistically significant, small effect, it might be nullified over the long term.
Originally developed as a cancer drug, bardoxolone was later scuttled by Reata almost a decade ago as a chronic kidney disease drug due to deaths in a Phase III trial.
Reata went back and ran the Phase III trial, which wrapped up four years ago, and on which this application is based.
Editor’s note: Article updated with stock price reaction and comments from Baird’s Skorney.