USA – An FDA advisory committee has delivered a crushing blow to Reata Pharma, voting unanimously that the drugmaker’s data on bardoxolone – a drug used to treat kidney disease – did not demonstrate efficacy.

Following earlier clinical trial failures with the drug in chronic kidney disease (CKD), and diabetic kidney disease, Reata is seeking approval from the US regulator for bardoxolone as a treatment for CKD caused by Alport syndrome, a rare genetic disease.

According to the FDA, the rare genetic disease can cause progressive loss of kidney function and kidney failure, as well as deafness and potential vision loss.

The company stated in a statement that the FDA advisory committee “voted no on whether the provided evidence demonstrated that bardoxolone is effective in slowing the progression of CKD in patients with Alport syndrome and that its benefits outweighed its risks.”

The data from the pharmaceutical company do not show that the drug is effective at slowing the loss of kidney function or lowering the risk of accumulation leading to kidney failure, according to a briefing document released by the regulator’s review team.

The company also failed to submit data from an animal model of Alport syndrome, as well as “other adequate and well-controlled clinical trials in Alport Syndrome or CKD” demonstrating the treatment’s ability to prevent kidney function loss.

Advisors also expressed reservations about the drug’s safety and the design of the pivotal trial used to support the marketing application.

The news is also a huge disappointment for patients and caregivers, as there are currently no FDA-approved therapies for Alport syndrome, which affects between 30,000 and 60,000 people in the United States.

In severe cases, the disease causes progressive kidney damage, with patients frequently requiring dialysis.

No throwing in the towel

Reata CEO Warren Huff stated that the company continues to believe that “the scientific evidence supports bardoxolone approval in the United States,” and that it will “work with the FDA to answer any questions they may have.”

The FDA is not required to follow the advice of its expert advisors, but it does so in most cases. It plans to make a decision on its review of bardoxolone by February 25 of next year.

The drug met its primary goal of improving estimated glomerular filtration rate (eGFR), a marker of kidney function, in the phase 3 CARDINAL trial that supported Reata’s filing for bardoxolone.

While bardoxolone met its primary and key secondary goals in the CARDINAL phase 3 trial, the FDA’s review team questioned whether the drug actually slowed disease progression.

However, in briefing documents filed prior to the advisory committee meeting, an FDA reviewer expressed concerns about the clinical significance of the data and whether it truly demonstrated a slowing in the progression of kidney disease.

The drug has a long history of development. Reata and AbbVie formed a partnership in the early 2010s, with deals totaling more than US$800 million.

In 2012, a data monitoring committee discovered that patients with CKD in a phase 3 study experienced a higher rate of heart-related side effects. In response, Reata halted the program, laid off half of its employees, and went back to the drawing board.

Then, in 2014, it entered a midstage study in a different indication. Since then, the company has tested the drug in a variety of rare CKDs in addition to Alport syndrome.

The drug is also being tested in a 550-patient pivotal trial in patients with autosomal dominant polycystic kidney disease, as well as a 70-patient midstage study in people with CKD who are at high risk of progressing to end-stage kidney disease, according to Fiercepharma

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