Reata's kidney med bardoxolone delivers in phase 3, teeing up FDA filing

Green light
Showing a sustained benefit even after being weaned off the drug shows the treatment improved the structure of the kidney, Reata CEO Warren Huff told FierceBiotech. (Stock Snap/Pixabay)

Just one month after ending a nine-year partnership with AbbVie, Reata Pharmaceuticals is delivering phase 3 data for its lead program in a rare form of chronic kidney disease (CKD)—and looking ahead to a potential FDA filing.

Patients who received the drug had better kidney function after 48 weeks of treatment and sustained that improvement after stopping the drug for four weeks.

The Cardinal study pitted the pill, bardoxolone methyl, against placebo in 157 patients whose CKD stems from Alport syndrome, which is caused by a mutation in the genes that code for a type of collagen. The syndrome progressively saps the kidney’s ability to filter blood, eventually leading to dialysis, end-stage kidney disease or a kidney transplant.

At the 48-week mark, patients who took bardoxolone had a better estimated glomerular filtration rate (eGFR) than placebo, meaning their kidneys were able to filter blood more quickly, Reata said in a Monday statement.

Looking ahead to the Cardinal data release, Reata CEO Warren Huff said earlier this year that the company anticipated an FDA filing some four to six months afterward. "It should be eligible for priority review; it's a deadly disease with no approved therapy. The drug is designed to give evidence modifying the course of disease."

Lisa Bonebrake, executive director of the Alport Syndrome Foundation, called the first-year results from Cardinal "very promising."

"This provides hope to the entire Alport syndrome community that we could finally have the first therapy to treat this rare, genetic kidney disease,” Bonebrake said in the statement.

After the 48 weeks of treatment, the Cardinal protocol required a four-week withdrawal period. Bardoxolone patients' eGFR fell about 46% after the withdrawal, but that still marked a significant improvement over placebo.

Although the study design took patients off treatment for four weeks, it was just a regulatory endpoint: “You would never withdraw in real life,” Huff said.

“When we talk to nephrologists, they always wonder why are we doing that? They would never take a patient off the drug,” Huff said. “We explain that it’s a regulatory endpoint, that the FDA wants to see as evidence that this drug will delay dialysis down the road.”

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Showing a sustained benefit even after being weaned off the drug shows the treatment improved the structure of the kidney, Huff said. It was the best way to prove reversal of kidney damage.

And Reata’s not done yet—after the withdrawal period, the study is putting patients back on the drug for another year. The one-year data may be enough for an accelerated approval for bardoxolone, but two-year data may support full approval of the drug, the company said in its statement.

Meanwhile, Reata will pay ex-partner AbbVie $330 million to regain the rights to bardoxolone; $75 million will come by the end of the year, with the remainder to be settled in 2020 and 2021.

RELATED: Reata’s bardoxolone hits goals in phase 2 kidney disease trial

Bardoxolone—and Reata, for that matter—have had quite the journey. The company inked a pair of deals with AbbVie in the early 2010s that totaled more than $800 million. But it hit a snag in 2012 when a data monitoring committee found that CKD patients who got bardoxolone in a phase 3 study experienced a higher rate of heart-related side effects. Reata pulled the plug on the program, cut its staff in half and went back to the drawing board.

In 2014, it pushed bardoxolone into phase 2 development in a new indication, pulmonary arterial hypertension, and started testing another drug, RTA 480, or omaveloxolone, in lung cancer, melanoma and Friedreich’s ataxia. Since then, it has tested bardoxolone in four types of rare CKD in addition to Alport syndrome.

Five years later, AbbVie walked away from their partnership, but Huff said this was a reflection of the company AbbVie had become and its retreat from kidney disease.

“We did this deal many years ago and at the time we did it, [Abbott] was very actively involved in the kidney space … After their spinout and other events, my impression is they redirected their development strategy to concentrate in autoimmune disease and oncology and really exited the renal-cardiovascular space,” he said.

“And so, the partnership had not been very active in recent years but had these remnant commercialization rights to our products. It’s actually to their credit that they understood the products needed to get to the patients and we’re happy that they engaged with us and we got this question settled.”