Amgen deploys patients to defend troubled Tavneos in FDA hearing request

 

Facing pressure around the world to withdraw the rare kidney disease drug Tavneos, Amgen has launched a robust defense with real-world evidence to support the product’s benefit-risk profile.

Amgen has launched a full-court press to defend the rare disease drug Tavneos, seeking a hearing before the FDA as the U.S. regulator presses the pharma to withdraw the drug from the market.

“Amgen strongly disagrees with the FDA’s proposal to withdraw Tavneos from the U.S. market,” the company said in a statement issued Friday. A day earlier, Amgen submitted a data and analyses package to the FDA to request a hearing with the regulator to discuss the drug’s future. Tavneos was approved in 2021 for ANCA-associated vasculitis (AAV).

The trouble for Tavneos began earlier this year, when the FDA asked Amgen in January to pull it from the market, citing liver toxicity issues that affected the drug’s overall risk-benefit profile. Then, in April, news emerged that 20 patients in Japan had died after taking the drug, which is marketed there by Amgen’s partner Kissei Pharmaceutical. Most of the deaths were related to vanishing bile duct syndrome (VBS), a complication of drug-induced liver injury (DILI). Kissei recommended that doctors stop offering the therapy to new patients, but quickly reversed the recommendation.

Since then, the FDA and European Medicines Agency have recommended that the drug be withdrawn from the market and a key study underpinning the approval decisions has been withdrawn from The New England Journal of Medicine.

Amgen acquired Tavneos in 2022 through the $3.7 billion takeover of ChemoCentryx.

Now, the company has revealed its full defense. Amgen argues that Tavneos met regulatory requirements for demonstrating substantial evidence of effectiveness and has a favorable benefit-risk profile. But Amgen acknowledged “the unique challenges of drug development in rare disease settings” and urged the FDA to consider patient perspectives.

“We welcome the opportunity for a science- and patient-focused engagement with the FDA, where we will present the totality of scientific evidence supporting Tavneos, including its positive benefit-risk profile, the seriousness of AAV, the limitations and burden of existing treatment approaches, and the importance of preserving treatment options for patients,” the company said.

AAV is a rare autoimmune kidney disease that causes inflammation in the blood vessels, leading to organ damage. Patients are prescribed corticosteroids to stem the inflammation and hopefully push the patient into a state of remission. But those treatments can come with significant side effects, such as increased risk of serious infections, osteoporosis, diabetes, cardiovascular disease, weight gain and more, Amgen argued.

The company offered stories from people living with the disease who experienced challenges living on steroids and were able to taper down with Tavneos.

“Against this backdrop, patients and caregivers have described Tavneos as meaningful not only because of its role in disease management, but also because it may help reduce reliance on prolonged steroid exposure when used appropriately with standard therapy,” Amgen said.

To support its case, Amgen offered data and analyses from 71 published real-world studies around the world from more than 2,200 patients that support the drug’s benefit-risk profile.

Most recently, Amgen sponsored an independent study with Duke Clinical Research Institute to re-evaluate the primary outcomes of the earlier ADVOCATE trial that supported the drug’s approval. The re-adjudication confirmed that Tavneos worked as well as the steroid prednisone for remission at week 26, with sustained remission at week 52, according to the company’s Friday release. The results occurred even though patients in the Tavneos arm had an 81% mean reduction in glucocorticoid use, whereas the prednisone arm had just a 56% reduction.

The study did not, however, show that Tavneos was superior to prednisone at week 52, Amgen said. But the results were overall similar to the ADVOCATE results, which have come under scrutiny.

Amgen also offered real-world studies, which the company claims show a high rate of disease control including a 93% remission rate at one year of treatment with Tavneos.

The company also looked at safety data in the post-marketing environment, finding that there were about 31 serious hepatic adverse events reported per 1,000 patient years. Most were reversible lab abnormalities but there were some deaths from VBS, particularly in Japanese patients over 65 years old. All of these events occurred within 90 days of the patient initially receiving Tavneos.

“Hepatotoxicity was identified during the Tavneos clinical development program and informed liver monitoring recommendations included in the U.S. Prescribing Information since initial approval,” Amgen said.

The company proposed an update to the drug’s label in 2024 to include a clearer warning about liver toxicity. This became effective on May 29 of this year.

“Tavneos should be evaluated through every relevant lens: independent re-adjudication of the ADVOCATE primary outcomes, real-world evidence, post-marketing safety data, patient need and physician judgment,” Amgen argued. “Across that record, the evidence supports continued confidence in Tavneos and its role as an important option for appropriate patients living with a serious rare disease and limited alternatives.”

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