Amgen Statement on FDA Data Submission for TAVNEOS® (avacopan)

Amgen Statement on FDA Data Submission for TAVNEOS^® (avacopan)

At Amgen, our mission is to serve patients. We take this mission seriously and it guides every decision that we make. There are more than 30 million patients in the United States living with a rare disease. On average, these individuals endure a journey of five years or more to receive an accurate diagnosis, and a much longer wait to get an effective treatment - if one even exists. For patients who have found appropriate treatment, their real-world experience contributes to our understanding of how medicines perform beyond clinical trials and helps to inform better care and better treatment decisions.

In recent months, there has been heightened focus on TAVNEOS^® (avacopan), an important treatment option for people living with severe active ANCA-associated vasculitis (AAV). ANCA-associated vasculitis is a rare, serious and potentially life-threatening disease that can cause irreversible organ damage. For many AAV patients, achieving and sustaining remission and reducing exposure to steroids, with their known and serious toxicities, remain important treatment goals. This is consistent with what we continue to hear from patients, physicians and the broader AAV community about the importance of maintaining access to this vital medicine. Currently, TAVNEOS is one of very few treatment options available for people living with severe active AAV.

On July 23, 2026, Amgen submitted data and analyses to the U.S. Food and Drug Administration (FDA) in support of its request for a hearing on TAVNEOS, with the goal of preserving access to the medicine in the United States.

Amgen strongly disagrees with the FDA's proposal to withdraw TAVNEOS from the U.S. market. Our submission includes extensive scientific analyses demonstrating that TAVNEOS meets the statutory standard for substantial evidence of effectiveness. Based on the totality of the evidence, we continue to believe TAVNEOS has a favorable benefit-risk profile and remains an important treatment option for appropriate patients.

Amgen and the FDA share a commitment to patients with rare diseases, including recognition of the unique challenges of drug development in rare disease settings and the importance of incorporating patient experiences and perspectives throughout that process. 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.

TAVNEOS is available for patients living with severe active GPA/MPA in the United States. Patients or providers with questions can learn more here.

More details on Amgen's submission to the FDA, the seriousness of living with and treating AAV, and the totality of available TAVNEOS data can be found below.

Burden of Living with AAV

Approximately 80-90% of patients with AAV present with kidney- or other organ-threatening manifestations, underscoring the serious nature of this disease. Continued availability of effective treatments matters because patients with severe active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two forms of AAV, face difficult treatment tradeoffs and have limited approved treatment options. AAV can cause a wide range of symptoms affecting multiple organs, including kidney problems, lung issues such as difficulty breathing or bleeding in the lungs, sinus and nasal inflammation, skin rashes, numbness and weakness, and eye inflammation with vision changes or loss. Because of the frequency of kidney involvement by AAV, many patients are left with significant chronic kidney disease, including organ failure.

Removing TAVNEOS from the market would significantly narrow the choices available to physicians and patients and would leave some patients more dependent on treatment regimens that carry their own serious and well-established burdens, including prolonged steroid exposure.

For many patients, the burden of long-term steroid use is significant. It can affect nearly every aspect of daily life - from physical health and emotional well-being to quality of life like the ability to work, care for family and maintain independence. Long-term steroid use is also associated with serious cumulative side effects, including an increased risk of serious infections, osteoporosis, diabetes, cardiovascular disease, weight gain and other complications. Reducing that burden has long been an important treatment goal for patients and the physicians who care for them.

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.

Patients living with rare, serious diseases should have the opportunity, in partnership with their healthcare providers, to consider all treatment options based on individualized benefit-risk considerations. That opportunity should not be narrowed.

Totality of Evidence

The totality of evidence for TAVNEOS comes from clinical trials, post-marketing real-world evidence, and post-marketing safety data. Since its approval in 2021, the evidence base supporting a consistent, favorable benefit-risk profile of TAVNEOS has continued to build to include more than 70 published real-world studies globally involving more than 2,200 reported patients^1-12. These data support confidence in the overall benefit-risk profile of TAVNEOS when used appropriately and reinforce its role as a meaningful option for patients, including as part of treatment approaches that may help reduce steroid exposure. The most recent studies provide additional information to support appropriate monitoring, patient selection, and informed use in clinical practice.

• Duke Clinical Research Institute Independent Re-Adjudication: In 2026, Amgen sponsored an independent, fully blinded re-adjudication, conducted by Duke Clinical Research Institute, evaluating the primary outcomes of ADVOCATE to address the FDA-cited concerns around the process followed by ChemoCentryx in 2019, prior to our acquisition of the company. The independent 2026 re-adjudication confirmed noninferiority of TAVNEOS versus a prednisone taper for remission at Week 26 (68.1% vs 67.1%; difference, 2.2%; 95% CI, −7.5 to 11.9) and sustained remission at Week 52 (61.4% vs 52.4%; difference, 9.8%; 95% CI, −0.3 to 19.9). These results strengthen confidence in TAVNEOS' efficacy. Additionally, these outcomes were achieved despite a substantial reduction in glucocorticoid exposure in the TAVNEOS arm (81% median reduction; 56% mean reduction) compared to the prednisone taper arm. Although superiority was not demonstrated at week 52 in the TAVNEOS arm vs. prednisone taper arm, in contrast to the original analysis, the overall findings remained similar to the original ADVOCATE results with a treatment effect that directionally favored TAVNEOS for sustained remission (re-adjudication week 52 difference 9.8% [95% CI, −0.3 to 19.9] and original week 52 difference 12.5% [95% CI, 2.6% to 22.3%] for TAVNEOS vs prednisone taper).
• Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis: In this systematic literature review and meta-analysis of 71 real-world studies, TAVNEOS was associated with high rates of disease control, including 87% remission at 6 months (23 studies; n=807), 93% remission at 12 months (12 studies; n=362), 86% sustained remission at 12 months (8 studies; n=283), and a 7% relapse rate at 12 months (12 studies; n=353). Across studies, only 36% of patients remained on glucocorticoids at both 6 and 12 months, mean eGFR improved by approximately 18 mL/min/1.73 m², and 66% of dialysis-dependent patients were liberated from dialysis. Safety outcomes included 11% of patients with any hepatotoxicity (32 studies; n=2,206), 7% with serious hepatotoxicity (10 studies; n=1,239), and 7% with serious infections (28 studies; n=1,986), with higher hepatotoxicity rates observed in Japanese cohorts, supporting the importance of continued liver function monitoring in clinical practice.
• Effectiveness and Safety of TAVNEOS in ANCA-Associated Vasculitis: Real-world evidence is important for evaluating the effectiveness of medicines when used in day-to-day practice. Findings from this large comparative effectiveness study were directionally consistent with the broader evidence base. Compared with standard of care (SOC) alone, patients treated with TAVNEOS plus SOC had lower steroid exposure at 6 months (weighted total difference −559.7 mg [95% CI −814.2, −1.9]) and fewer relapses at 12 months (weighted HR 0.81 [95% CI 0.59-1.13]). Rare serious hepatic events occurred in both treatment groups. These results support the favorable benefit-risk profile of TAVNEOS.
• A Post-Marketing Evaluation of TAVNEOS Safety with a Focus on Hepatic Adverse Events: In this retrospective, descriptive analysis of the Amgen Global Safety Database, serious hepatic adverse events were reported at a rate of approximately 31 events per 1,000 patient-years. Most reported hepatic events were reversible laboratory abnormalities; however, serious liver injury and vanishing bile duct syndrome (VBDS), including fatal outcomes, were reported, predominantly from Japan in patients > 65 years old. All VBDS cases occurred within 90 days of TAVNEOS initiation. Hepatotoxicity was identified during the TAVNEOS clinical development program and informed liver monitoring recommendations included in the U.S. Prescribing Information since initial approval. Continued review of the global post-marketing safety database further characterized the hepatic safety profile and informed Amgen's proposed update to the U.S. Prescribing Information in 2024, which culminated in the updated hepatotoxicity warning and monitoring recommendations that became effective on May 29, 2026. By communicating these findings, Amgen aims to reinforce appropriate liver monitoring and support the safe and informed use of TAVNEOS in clinical practice.

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. 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.

People living with rare diseases deserve treatment decisions informed by rigorous science, real-world evidence, and their lived experiences. We believe the hearing process provides the appropriate forum to fully evaluate that evidence before any final decision affecting patients is made.

Our full FDA submission is available here. Comments from patients and the provider community on the FDA's withdrawal proposal can be found here.

INDICATION

TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti- neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Serious hypersensitivity to avacopan or to any of the excipients.

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. In the postmarketing setting, vanishing bile duct syndrome (VBDS) as a consequence of liver injury, including cases with a fatal outcome, has been reported. These events occurred predominantly in Japan in patients aged 65 years and older, but VBDS may affect patients of any age or ethnicity who are receiving TAVNEOS. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for 6 months and as clinically indicated thereafter. For patients of Japanese descent, consider more frequent laboratory testing: every 2 weeks after the start of therapy for the first 3 months, followed by laboratory testing every 4 weeks for the next 3 months of treatment, and as clinically indicated thereafter. If a patient receiving treatment with TAVNEOS presents with an elevation in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] to >3 times the upper limit of normal, evaluate promptly and consider pausing treatment as clinically indicated. If AST or ALT is > 5 times the upper limit of normal (ULN), or ALT or AST > 3 times the ULN with total bilirubin > 2 times the ULN, or alkaline phosphatase ≥ 2 times the ULN, or if the patient has clinical symptoms such as jaundice or pruritus, discontinue TAVNEOS until TAVNEOS-induced liver injury is ruled out. Immediately and permanently discontinue TAVNEOS if VBDS is suspected. TAVNEOS is not recommended for patients with active, untreated, and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before administering this drug to a patient with liver disease.

Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including 1 serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be readministered unless another cause has been established.

Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life-threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for 6 months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming.

Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in the TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection, or who have been to places where certain infections are common.

ADVERSE REACTIONS

The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia.

DRUG INTERACTIONS

Avoid co-administration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Consider dose reduction of CYP3A4 substrates when co-administering TAVNEOS. Co-administration of avacopan and 40 mg simvastatin increases the systemic exposure of simvastatin. While taking TAVNEOS, limit simvastatin dosage to 10 mg daily (or 20 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity). Consult the concomitant CYP3A4 substrate product information when considering administration of such products together with TAVNEOS.

TAVNEOS is available as a 10 mg capsule.

Please see Full Prescribing Information and Medication Guide for TAVNEOS.

To report a suspected adverse event, call 1-833-828-6367. You may report to the FDA directly by visiting https://www.fda.gov/medwatch or calling 1-800-332-1088.

References

1. Berke I, Keller F, Untersulzner C, et al. Systematic review of efficacy and safety of avacopan in real-world clinical practice. Kidney Int Rep. 2026;103753.
2. Bharania P, Geller M, Jana A, Mirkovic K, Wallace ZS, Bozeman A, Mehta S, Yoon B, Burton P. A Post-Marketing Evaluation of Avacopan Safety with a Focus on Hepatic Adverse Events. medRxiv. Published online July 22, 2026.
3. Chalkia A, Flossmann O, Jones R, et al. Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage. Nephrol Dial Transplant. 2024;39(9):1473-1482.
4. Draibe J, Espigol Frigolé G, Cid MC, et al. The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain. Rheumatology (Oxford). 2025;64(4):2019-2026.
5. Gabilan C, Belliere J, Moranne O, et al. Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicentre real-world study. Rheumatology (Oxford). 2025;64(4):2214-2219.
6. Ibiloye E, Kathe N, Mirkovic K, Martin C, Tu S, Gamburg R, Kumar J, Solanki G, Wallace ZS. Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis. medRxiv. Published online June 17, 2026.
7. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021;384:599-609.
8. Oh S, Wallace ZS, Dang L, Brookhart MA, Bozeman AM, Pham P, Lin TCJ, Motsko S. Effectiveness and Safety of Avacopan Added to Standard of Care Versus Standard of Care Alone in ANCA-Associated Vasculitis. medRxiv. Published online July 22, 2026.
9. Tagami G, Yamaguchi M, Sugiyama H, et al. Efficacy and safety of avacopan in antineutrophil cytoplasmic autoantibody-associated vasculitis: a retrospective cohort study in Japan. BMC Rheumatol. 2025;9(1):8.
10. van Leeuwen JR, Bredewold OW, van Dam LS, et al. Compassionate Use of Avacopan in Difficult-to-Treat Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Kidney Int Rep. 2022;7(3):624-628.
11. Zimmermann J, Sonnemann J, Jabs WJ, et al. Avacopan in Anti-Neutrophil Cytoplasmic Autoantibodies-Associated Vasculitis in a Real-World Setting. Kidney Int Rep. 2024;9(9):2803-2808.
12. Zonozi R, Aqeel F, Le D, et al. Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Kidney Int Rep. 2024;9(6):1783-1791.