Tavneos Liver Injury Risks, Faked Data Lead FDA To Seek Market Removal

Regulators approved Tavneos based on data from only one clinical trial, which the FDA recently discovered was manipulated to make the drug look effective.

Federal investigators say the autoimmune disease drug Tavneos, recently linked to life-threatening liver injury risks, should never have been approved because key clinical trial data was allegedly manipulated to overstate its effectiveness.

The U.S. Food and Drug Administration (FDA) sent the current owner of the drug, Amgen, a letter on April 27 announcing it was proposing to withdraw Tavneos from the market, due to both its ineffectiveness and “untrue statements of material fact in the application.”

First developed by ChemCentryx and approved by the FDA in October 2021, Tavneos (avacopan) is prescribed to adults with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, a rare autoimmune disease that causes inflammation in small blood vessels and can lead to organ damage, particularly affecting the kidneys and lungs.

Tavneos was supposed to work by blocking the complement 5a receptor, responsible for much of the inflammation linked to the disease. It was marketed as a targeted alternative to long-term steroid use. Since Tavneos was approved in 2021, it has been used by more than 7,000 patients, but an estimated 200 million to 400 million people worldwide are believed to suffer the affliction.

Tavneos Risks

In February, the FDA issued a drug safety communication, warning that side effects of Tavneos appeared to be linked to drug-induced liver damage. This followed reports of elevated liver enzymes and signs of acute liver damage in certain users of the medication. At least 74 cases involved serious liver complications, with 54 hospitalizations and eight deaths.

The agency reportedly asked Amgen to remove the drug from the market, but the manufacturer refused.

However, this recent letter indicates that the FDA is ready to force a Tavneos recall and remove the drug from the market permanently, revoking its approval. The letter, sent by the FDA’s Center for Drug Evaluation and Research (CDER), was addressed to Dr. Nicole Cheung, Amgen’s manager of Global Regulatory Affairs.

“CDER proposes to withdraw approval of TAVNEOS (avacopan), NDA 214487, because of new information, which was withheld from FDA and did not become known to FDA until more than three years after approval, indicating that there is a lack of substantial evidence of effectiveness for the drug, and the application contains untrue statements of material facts.”

– U.S. Food and Drug Administration Proposal to Withdraw Marketing Approval

The letter indicates that the FDA received new information that study personnel manipulated the data in ChemCentryx’s original New Drug Application. According to the agency, this manipulation was done because the real results showed Tavneos’s benefits were not statistically significant, meaning it did not work.

That clinical trial was the only data the FDA used to approve the drug for use on the market. However, the agency’s letter states that if it had been given accurate data, Tavneos would have been rejected.

Tavneos and VBDS

The FDA also notes that liver toxicity was one of the agency’s original concerns about the drug. Now, post-marketing data linking the drugs to liver injuries and patient deaths suggest Tavneos may be associated with vanishing bile duct syndrome (VBDS). This is a severe form of liver injury where the intrahepatic bile ducts are destroyed and disappear over time. It can lead to blocked bile flow (chronic cholestasis), severe liver functioning problems, and cause death within one to three years if not treated. VBDS patients often require a liver transplant.

The letter gives ChemoCentryx, an Amgen subsidiary, 30 days to notify the FDA that it seeks a hearing, and would have to provide the agency with data, information and analyses showing there is a “genuine and substantial issue of fact” with the FDA’s findings and call to have Tavneos withdrawn.

Patients currently taking Tavneos are urged to consult their healthcare providers before making any changes to treatment and seek immediate medical attention if symptoms of liver injury occur. Adverse events should be reported to the FDA through the MedWatch Safety Information and Adverse Event Reporting Program, either online, by regular mail or by fax at 1-800-FDA-0178.

Sign up for more safety and legal news that could affect you or your family.