A Reata Pharmaceuticals drug for rare kidney disease is on the market be rejected Approved by the FDA, if the company wants another regulatory review, it will have to conduct another clinical trial to address the agency’s concerns.
The Reata drug bardoxolone is an experimental treatment for Alport syndrome. This disorder is a rare genetic disorder that causes chronic kidney disease. The FDA letter, which casts doubt on the drug’s efficacy data, largely echoes concerns raised by an FDA advisory committee, according to the company.last December, that committee vote Against the proposed approval of bardoxolone. Specifically, the committee voted unanimously on whether the evidence demonstrated the drug’s efficacy in slowing the progression of chronic kidney disease in people with Alport syndrome and that the drug’s benefits outweighed its risks.
Plano, Texas-based Reata CEO Warren Huff said in a prepared statement that the company will continue to work with the FDA to confirm the next steps for the Alport syndrome program.
Alport syndrome can affect children and adults. It is caused by mutations in genes encoding a family of proteins important for the structural components of the kidney. The disease causes the organs to gradually lose their ability to filter waste from the blood. Patients may progress to end-stage renal disease requiring long-term dialysis treatment or kidney transplantation. There are no FDA-approved treatments for chronic kidney disease caused by Alport syndrome.
Bardoxolone is an oral medication that is taken once a day. The small molecule was designed to target and activate Nrf2, a transcription factor that restores the function of mitochondria, the energy-producing components of cells. This approach is designed to stop inflammation that damages the kidneys.
Reata tested bardoxolone in a double-blind, placebo-controlled Phase 3 study of 157 patients. The participants were on medication for 100 weeks, followed by a 4-week washout period, during which they received no medication. The primary objective was to show changes in estimated glomerular filtration rate (eGFR), a measure of kidney function, after 100 weeks. A secondary objective was to evaluate patients after a four-week washout period. At the end of 2020, the company reported that preliminary result Show that the drug meets the primary and secondary objectives of the study.
inside FDA briefing document The design of the phase 3 study did not allow an assessment of bardoxolone’s potential to slow disease progression, the agency said in preparation for an advisory committee meeting on Dec. 8, 2021. The FDA said that the eGFR values collected at weeks 52 and 104 still represented the reversible effects of the drug, as assessed by the FDA’s model and the company’s model, “and neither model showed that bardoxolone slowed decline in kidney function. progress,” the FDA said.
FDA’s complete response letter is not a public document. According to Reata, the FDA said evidence of efficacy may come from a well-controlled study showing a clinically relevant effect on the rate of kidney function loss in patients with Alport syndrome. Alternatively, the study could show an impact on clinical outcomes, such as capturing how these patients feel, function or survive.
According to the FDA briefing document, the independent data monitoring committee has three main concerns about the pivotal bardoxolone study: higher all-cause mortality in the treatment group compared to the placebo group; excess fluid in the body leading to fluid overload, including cardiac Serious adverse events including exhaustion (these problems appear to be limited to the first 4 weeks of treatment); and a risk-benefit profile that appears to be detrimental to safety. While there were no reports of heart failure in the pivotal clinical trial, the study was designed to exclude patients with a history of heart failure or heart disease. The FDA still wants the company to address whether bardoxolone has clinically relevant effects on the heart.
Bardoxolone is key to Reata, which includes most of its drug pipeline. In addition to Alport syndrome, the company has advanced a separate clinical trial of the compound to test it as a treatment for chronic kidney disease associated with five other diseases. What happens with bardoxolone may affect another Reata drug. Omaveloxolone acts similarly to bardoxolone and has reached pivotal testing in the neurological disorder Friedreich’s ataxia.
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