What Is Avacopan?
Avacopan, also known by its brand name TAVNEOS, is an orally active medication that functions as a complement 5a receptor (C5aR) antagonist. This means it works by blocking the activity of the C5a receptor, which is involved in the body's inflammatory response. By targeting this receptor, avacopan aims to reduce inflammation and prevent tissue damage in various conditions. It is being investigated in clinical trials for its potential to treat diseases characterized by excessive inflammation and immune system overactivity. The medication is delivered in capsule form.
Uses and Conditions Under Study
Avacopan is currently being investigated in clinical trials for several inflammatory and autoimmune conditions. A significant focus is on ANCA-Associated Vasculitis (AAV), a group of rare autoimmune diseases that cause inflammation of small blood vessels. This includes conditions such as ANCA-Associated Vasculitis (AAV), Antineutrophil Cytoplasmic Antibody-associated Vasculitis, and Antineutrophil Cytoplasmic Antibody Positive Vasculitis, which are being studied across 4 trials. Avacopan may help by modulating the inflammatory response that drives these conditions.
Another area of investigation is C3 Glomerulopathy (C3G), a rare kidney disease characterized by abnormal activation of the complement system, leading to C3 protein deposits in the kidneys. There is currently no approved treatment for C3G, and avacopan is being studied in 1 trial for its potential to address the underlying complement activation. Diffuse Alveolar Hemorrhage (DAH), a severe condition where bleeding occurs in the lungs, is also being explored in 1 trial, as it can be a complication of vasculitis.
Avacopan is also being studied in 1 trial for End-Stage Renal Disease (ESRD), a condition where kidneys can no longer function on their own, often as a result of chronic kidney diseases like C3G or AAV. Additionally, it is being investigated for Acne Inversa (also known as Hidradenitis Suppurativa), a chronic inflammatory skin condition, in 1 trial.
Dosing
Avacopan is administered orally, typically in capsule form. The brand name for avacopan is TAVNEOS. Clinical trials have studied various strengths and dosing regimens. One common dosage investigated is 30 mg taken twice daily (BID). The capsules are available in strengths ranging from 3 mg to 10 mg, allowing for flexible dosing to reach the target amount.
For patients with Diffuse Alveolar Hemorrhage (DAH), avacopan capsules have been studied for administration via nasogastric tube, where the capsules are solubilized in heated water before delivery. Avacopan has also been studied in combination with other treatments, such as short-term reduced-dose prednisolone and rituximab, or as part of a standard of care (SoC) regimen. Investigational dosing has also explored 10 mg and 30 mg strengths, and its use in patients with varying renal and hepatic functions, including those with End-Stage Renal Disease requiring hemodialysis.
Side Effects
In clinical trials, the most common side effect experienced by patients taking Avacopan was headache. In studies involving 514 patients, 3.9% experienced headache, compared to 3.4% of patients taking a placebo.
Other common side effects reported in these larger trials included:
- Increased liver enzymes (alanine aminotransferase): 2.7% of patients on Avacopan compared to 2.5% on placebo.
- Upper respiratory tract infection: 2.1% of patients on Avacopan compared to 4.5% on placebo.
- Nausea: 1.6% of patients on Avacopan compared to 4.1% on placebo.
In a separate, smaller study involving 28 patients, some side effects were reported at higher rates with Avacopan compared to placebo. These included:
- Peripheral swelling (oedema peripheral): 17.9% of patients on Avacopan compared to 3.4% on placebo.
- Vomiting: 14.3% of patients on Avacopan compared to 3.4% on placebo.
- Increased blood creatine phosphokinase (an enzyme): 10.7% of patients on Avacopan compared to 3.4% on placebo.
- Low white blood cell count (lymphopenia): 10.7% of patients on Avacopan compared to 0.0% on placebo.
- Decreased appetite: 10.7% of patients on Avacopan compared to 0.0% on placebo.
Clinical Trial Results
ANCA-Associated Vasculitis
In a Phase 3 clinical trial (NCT02994927) for ANCA-associated vasculitis, Avacopan was compared to prednisone. At Week 26, 72.3% of patients taking Avacopan achieved disease remission, which was similar to the 70.1% of patients on prednisone. However, at Week 52, Avacopan showed a higher rate of sustained disease remission, with 65.7% of patients maintaining remission compared to 54.9% on prednisone.
Patients treated with Avacopan also experienced a lower rate of disease relapse. Only 10.1% of Avacopan patients experienced a relapse after achieving remission, compared to 21.0% of patients on prednisone. Additionally, Avacopan treatment was associated with a lower glucocorticoid-induced toxicity index, suggesting less steroid-related side effects. Patients on Avacopan showed a greater improvement in kidney function, with an average increase in eGFR of 5.8 to 7.3 mL/min/1.73 m^2 over 52 weeks, compared to 2.9 to 4.1 mL/min/1.73 m^2 for prednisone.
C3 Glomerulopathy
A controlled trial (NCT03301467) evaluating Avacopan in C3 glomerulopathy showed positive effects on kidney function. Over 26 weeks, patients taking Avacopan experienced an average increase in eGFR of 0.47 mL/min/1.73m^2, while those on placebo saw a decrease of 3.35 mL/min/1.73m^2. This represented a 4.79% improvement in eGFR for Avacopan patients compared to a 5.88% decrease for placebo patients.
Avacopan also led to a greater reduction in proteinuria, with a 26% decrease in urine protein-to-creatinine ratio (UPCR) compared to a 14% decrease with placebo. Furthermore, Avacopan showed an improvement in kidney tissue health, with a 5.77% decrease in the C3G Histologic Index for Disease Activity, whereas the placebo group showed a 26.20% increase, indicating worsening.
Hidradenitis Suppurativa (HS)
In a study (NCT03852472) for moderate to severe hidradenitis suppurativa, the 30 mg dose of Avacopan demonstrated a Hidradenitis Suppurativa Clinical Response (HiSCR) in 35.1% of participants at Week 12, compared to 30.8% for placebo. The 30 mg dose also led to a greater reduction in inflammatory nodule count, decreasing by an average of 3.9 nodules from baseline, compared to 2.4 nodules for placebo. The overall severity of HS, as measured by the IHS4 score, improved by an average of 9.8 points with 30 mg Avacopan, compared to 6.4 points with placebo.
Renal Function in End-Stage Renal Disease (ESRD)
A study (NCT06468826) investigated the safety of Avacopan in participants with normal renal function and those with end-stage renal disease (ESRD) requiring hemodialysis. The study reported a low incidence of treatment-emergent adverse events (TEAEs) and no serious adverse events (SAEs) in any of the groups, suggesting a favorable safety profile in these populations.
Currently Recruiting Trials
Avacopan is currently being investigated in several clinical trials, offering opportunities for patients to contribute to medical research. These studies aim to understand more about how Avacopan works, its effectiveness, and its safety in treating various conditions, particularly those involving inflammation and autoimmune responses.
- A Phase 1 study, NCT07556484, sponsored by Mayo Clinic, is exploring the pharmacokinetics of emulsified Avacopan. This trial is for patients with active severe Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA) who also have diffuse alveolar hemorrhage (DAH) requiring mechanical ventilation. The study seeks to determine how the body processes Avacopan at a dose of 30 mg twice daily over 72 hours in up to 6 participants.
- Mayo Clinic is also sponsoring a Phase 2 study, NCT06676579, focusing on Avacopan for crescentic Immunoglobulin A Nephropathy (IgAN). This trial aims to evaluate the efficacy and safety of Avacopan when combined with low-dose glucocorticoids in patients with IgAN who are at high risk of disease progression. It plans to enroll 16 participants.
- Chiba University is conducting a Phase 4 trial, NCT06611696, comparing Avacopan with reduced-dose glucocorticoids in ANCA-associated vasculitis (AAV). This study investigates if Avacopan, alongside short-term (4 weeks) reduced-dose glucocorticoids and rituximab, is effective for newly-onset AAV, and also assesses its long-term safety. The trial targets an enrollment of 160 patients.
- Amgen is sponsoring a Phase 3 study, NCT06321601, to explore the efficacy of Avacopan in children with AAV. This trial is open to participants from 6 years to less than 18 years of age and aims to enroll 20 children.
- Another Amgen-sponsored Phase 4 study, NCT06072482, is evaluating the long-term safety of Avacopan in participants with ANCA-associated vasculitis (AAV). This study is designed to enroll 300 participants.
- Kissei Pharmaceutical Co., Ltd. is conducting a Special Drug Use-results Survey, NCT06758271, for the long-term use of Avacopan. This survey evaluates the safety and efficacy of Avacopan in Japanese patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) under real-world conditions. It plans to include 250 patients.
Where to Participate
Clinical trials for Avacopan are reaching patients across a wide geographic area, with studies active in 67 sites across 62 cities and 31 states. This broad reach helps ensure diverse patient populations can participate in research.
Some of the top locations with multiple active sites include:
- Pittsburgh, Pennsylvania (3 sites)
- Rochester, Minnesota (3 sites)
- Boston, Massachusetts (2 sites)
- Atlanta, Georgia (2 sites)
- Minneapolis, Minnesota (2 sites)
- Jacksonville, Florida (2 sites)
- Cleveland, Ohio (2 sites)
Eligibility for these trials generally includes individuals aged 6 to 100 years, of all genders. Healthy volunteers are typically not included, but children are eligible for specific studies.
Development Timeline
The journey of Avacopan in clinical development began on December 16, 2016, with the latest trial projected to conclude on April 29, 2026. Over this period, a total of 15 clinical trials have been initiated, involving 1,862 participants.
Early development explored Avacopan for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the focus soon expanded significantly, with a strong emphasis on autoimmune and inflammatory conditions. Major sponsors like Amgen, with 9 trials, and Mayo Clinic, with 2 trials, have been instrumental in driving this research.
The pipeline broadened to include a range of conditions, notably various forms of vasculitis, such as ANCA-associated vasculitis (AAV), Granulomatosis with Polyangiitis (GPA), and Microscopic Polyangiitis (MPA). Other indications explored include IgA Nephropathy (IgAN), C3 Glomerulopathy (C3G), Diffuse Alveolar Hemorrhage, and Hidradenitis Suppurativa. Avacopan has progressed through all phases of clinical development, including Phase 1, Phase 2, Phase 3, and Phase 4 studies, demonstrating a comprehensive evaluation of its potential therapeutic benefits and safety profile across a growing spectrum of diseases.