FDA proposes removing Tavneos from market over data concerns
Oral treatment was approved for most common forms of AAV in 2021
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Following allegations of manipulated data in its regulatory application, a division of the U.S. Food and Drug Administration (FDA) has proposed withdrawing Tavneos (avacopan), an oral treatment approved for the most common forms of ANCA-associated vasculitis (AAV), from the market.
In a press announcement, the FDA’s Center for Drug Evaluation and Research (CDER) said it is recommending withdrawing Tavneos’ approval “because new information indicates that Tavneos has not been shown to be effective for its approved use, and because the application that resulted in FDA approval contained untrue statements of material fact.”
“CDER can no longer conclude that there is, or has ever been, a valid demonstration that Tavneos is effective for its approved use,” the CDER said.
Similar allegations have also led to an ongoing regulatory reevaluation of Tavneos in Europe.
Tavneos’ approvals based mainly on data from Phase 3 trial
Tavneos is an oral medication that works by blocking the activity of a component of the complement cascade, a group of immune proteins whose overactivation is involved in AAV.
It was approved by the FDA in 2021 for the treatment of adults with severe and active microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA), the most common types of AAV. The approval covers use of Tavneos as an add-on to standard treatment, including glucocorticoids. The therapy was approved in Europe for a similar indication in 2022.
Tavneos’ approvals were based mainly on data from the Phase 3 ADVOCATE clinical trial (NCT02994927), which tested Tavneos against a glucocorticoid as an add-on to standard treatments in adults and adolescents with MPA or GPA. The trial was reported to meet its goal, with Tavneos at least as effective as glucocorticoids in inducing disease remission.
However, the CDER now says that new information, which didn’t become public until three years after the original approval, “shows that unblinded study personnel manipulated the results of [ADVOCATE] so the drug looked effective when the original analysis did not support that conclusion.”
The CDER said that Chemocentryx, the company that originally developed Tavneos, did not disclose the original analysis to the FDA, which is a violation of the agency’s regulations.
FDA also voices concerns about treatment’s safety profile
The FDA has also raised concerns about Tavneos’ safety profile, particularly regarding liver health. The therapy’s prescribing information notes that liver damage is a potential risk, but according to the CDER, there have been reports of fatal liver injury related to the drug, which is not listed as a possibility in the prescribing information.
A rare liver complication called vanishing bile duct syndrome — marked by damage to a series of tubes that normally carry the digestive fluid bile from the liver to the intestines — has also been documented, despite not being reported in the therapy’s prescribing information.
Amgen acquired Chemocentryx in 2022 and now markets Tavneos in the U.S. CSL Vifor Pharma holds the therapy’s rights in Europe and most other parts of the world.
Earlier this year, as new information about allegedly manipulated trial data were coming to light, the FDA asked Amgen to pull Tavneos from the U.S. market voluntarily — but the company declined.
In the interim, we recommend that health care professionals discuss Tavneos and other available treatments with their patients to decide whether to use or continue to use Tavneos while a final decision is being made about the drug’s marketing status.
In a letter to healthcare providers published earlier this month, the company said: “We remain confident that TAVNEOS is an important and effective medicine for severe active ANCA-associated vasculitis based on robust clinical data and real-world evidence demonstrating the effectiveness and favorable benefit–risk profile.”
Amgen said it “continues to work with the FDA to determine next steps, while keeping patient safety, needs, and support at the forefront.”
Once the CDER’s proposal is formally published, Amgen will have the opportunity to request a hearing. The FDA commissioner can then decide whether or not to grant one. In the meantime, Tavneos will remain on the market until either Amgen voluntarily withdraws it or the FDA commissioner mandates its removal.
“In the interim, we recommend that health care professionals discuss Tavneos and other available treatments with their patients to decide whether to use or continue to use Tavneos while a final decision is being made about the drug’s marketing status,” the CDER wrote.
