EMA Approves MAA Review of Avacopan for ANCA-Associated Vasculitis

On November 3, 2020, biopharmaceutical company ChemoCentryx and global pharmaceutical company Vifor Pharma Group’s sub-business Vifor Fresenius Medical Care Renal Pharma (VFMCRP) announced that the European Medicines Agency will review the Marketing Authorization Application (MAA) for avacopan. Thus far, the orally administered treatment has been studied in relation to ANCA-associated vasculitis. The MAA review is a step in the right direction to provide new therapeutic offerings to patients with ANCA vasculitis.


Developed by ChemoCentryx, avacopan is a selective C5aR1-inhibitor. C5aR1 is a complement C5a receptor, meaning it plays a role in the complement system. According to the British Society for Immunology, the complement system:

refers to a series of >20 proteins, circulating in the blood and tissue fluids. Most of the proteins are normally inactive, but in response to the recognition of molecular components of microorganisms they become sequentially activated in an enzyme cascade – the activation of one protein enzymatically cleaves and activates the next protein in the cascade.

Basically, the complement system contributes to the immune system by fighting perceived invaders and causing inflammation. C5a is pro-inflammatory, which means it prompts inflammation in response to foreign invaders. According to GeneCards, C5aR1 also plays a role in conditions such as mast-cell sarcoma. By inhibiting C5A and C5AR1, avacopan prevents C5a over-activation. Additionally, avacopan should prevent vasculitis relapses.

Reviewing the Avacopan MAA

The EMA decided to review the Avacopan MAA based on data from the Phase 3 ADVOCATE trial. 331 patients with ANCA vasculitis enrolled. During the trial, researchers found that avacopan allowed for sustained and lasting remission from vasculitis symptoms in comparison with prednisone. Additionally, avacopan treatment improved kidney function and quality of life (QOL). The drug received Orphan Drug designation in the United States for the treatment of atypical hemolytic uremic syndrome (AHUS), C3 glomerulopathy (C3G), and ANCA vasculitis. In Europe, avacopan received Orphan Medicinal Product designation for the treatment of C3G, MPA, and GPA. Hopefully, the EMA will review the MAA and provide a response in 2021.

ANCA Vasculitis

Altogether, vasculitis refers to blood vessel inflammation. As blood vessels narrow, constrict, or otherwise restrict blood flow, patients’ organs and tissues become damaged. ANCA vasculitis occurs when anti-neutrophilic cytoplasmic autoantibodies (ANCAs) mistakenly attack the body. As the complement system becomes over-activated, these autoantibodies stimulate and attack a type of white blood cell called neutrophils. Between the ANCAs and the neutrophils, the blood vessels become inflamed, resulting in organ damage.

Granulomatosis with Polyangiitis (GPA)

As a rare blood vessel disease, granulomatosis with polyangiitis (GPA) is serious and potentially fatal without prompt diagnosis and treatment. When blood vessels become swollen and inflamed, it prevents cells from getting oxygen, causing tissue injury. In GPA, blood vessel inflammation occurs in both small and medium blood vessels. Typically, the condition impacts the lungs, kidneys, and sinuses. However, the eyes, ears, nerves, joints, and skin also may be affected. Symptoms include:

  • Coughing up blood
  • Frequent nosebleeds
  • Hearing loss
  • Skin rashes
  • Difficulty breathing or shortness of breath
  • Congestion
  • Fatigue
  • Fever
  • Night sweats
  • Joint and muscle pain
  • Loss of organ function

Microscopic Polyangiitis (MPA)

Doctors are not sure of the exact cause of microscopic polyangiitis (MPA), a rare condition under the umbrella of ANCA-associated vasculitis. MPA is characterized by blood vessel inflammation in the nervous system, kidneys, lungs, skin, and joints. Typically, MPA affects patients of all ages, genders, and ethnicities equally. Symptoms include:

  • Muscle and joint pain
  • Lowered mobility
  • Nerve damage
  • Fatigue
  • Coughing up blood
  • Bloody urine
  • Appetite loss
  • Fever
  • Difficulty breathing
  • Lung disease and/or respiratory failure
  • Unintended weight loss
  • Swelling in the lower extremities
  • Skin rashes
  • Kidney inflammation and failure
  • Aneurysms
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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