Earlier this year, Amgen refused the FDA’s request to withdraw Tavneos from the market. Now, two researchers who participated in the original study to support the drug’s approval claim they did not know the primary endpoint was readjudicated after the study was unblinded.
The New England Journal of Medicine has retracted a paper that presented pivotal data for Amgen’s Tavneos, adding to the pharma’s woes over its rare disease drug.
Two of the study’s authors requested the retraction, according to an NEJM note published June 29. The authors cited the ongoing investigation by the FDA into allegedly manipulated data that supported the approval of Tavneos. The drug was originally developed by ChemoCentryx and was approved for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis in 2021. Amgen acquired ChemoCentryx for $3.7 billion in August 2022.
“Without the knowledge of these two authors, the primary end-point assessments in nine patients were readjudicated after database lock and trial unblinding,” NEJM wrote on Monday. “This was not disclosed in the article and is inconsistent with proper research conduct.”
The retraction is the latest development in what has been a months-long tussle between the FDA and Amgen over Tavneos. The saga started in January, when the FDA asked Amgen to voluntarily pull the drug from the market, pointing to problems with how ChemoCentryx re-adjudicated efficacy data in its pivotal study. Amgen refused.
In late March, the agency attributed more than 70 cases of drug-induced liver injury (DILI) to Tavneos, including eight deaths. The vast majority of the patients who developed DILI had serious outcomes that needed medical attention.
Three of the patients who died and four who did not also had biopsy-confirmed vanishing bile duct syndrome, a side effect that Amgen had previously requested be added to the drug’s label, according to a company spokesperson who sent a statement to Endpoints News in March. The request was pending, the spokesperson said the time. A few weeks later, the FDA put out another announcement calling into question the integrity of the data used to support Tavneos’ approval.
“New information that only became known to CDER [Center for Drugs Evaluation and Research] more than three years after approval shows that unblinded study personnel manipulated the results of the pivotal clinical study so the drug looked effective when the original analysis did not support that conclusion,” the agency said in an April 27 statement.
Because of this, CDER “can no longer conclude that there is, or has ever been, valid demonstration that Tavneos is effective.”
Amgen, for its part, has consistently claimed that “patient safety guides every decision we make,” a spokesperson told BioSpace in April. “We remain confident in Tavneos as a safe and effective medicine, supported by years of clinical data and real-world evidence.”
The pharma earlier this month requested a hearing with the FDA and enlisted the Duke Clinical Research Institute to conduct an “independent and fully blinded re-adjudication” of the data that led to Tavneos’ approval. Amgen will also present findings from more than a dozen ongoing or recently completed studies to support the drug’s benefit-risk profile.
