In a recent press release, biopharmaceutical company ChemoCentryx announced FDA approval for a New Drug Application (NDA) for avacopan, a treatment for ANCA-associated vasculitis. According to the FDA, a New Drug Application is:

the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The goals of the NDA are to provide enough information to permit FDA reviewer to [determine] whether the drug is safe and effective, and whether the benefits outweigh the risks; [if its] proposed labeling is appropriate and what it should contain; [and] whether the methods used in manufacturing the drug and the controls used to maintain the drug’s quality are adequate to preserve the drug’s identity, strength, quality, and purity.

In this case, the NDA included data sourced from the Phase 3 ADVOCATE clinical trial. During the trial, researchers analyzed the safety, efficacy, and tolerability of avacopan for 331 patients with ANCA-associated vasculitis. The International trial included patients from 20 different countries. Patients received either prednisone and rituximab or cyclophosphamide, or avacopan with one of the associated drugs. Those who received the avacopan showed better health, quality of life (QOL), safety, tolerability, and kidney function.

Avacopan

Developed by ChemoCentryx, avacopan is a small molecule that inhibits selective complement 5a receptor (C5aR). The therapy, administered orally, blocks C5aR from activating destructive inflammatory cells (blood neutrophils). As a response, the cells cannot be damaged. Since blood vessel inflammation and damage drives ANCA-vasculitis, avacopan halts or greatly reduces this damage. It offers a safer and more efficient line of treatment than daily immunosuppressants.

ANCA-Associated Vasculitis

According to the NIH, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of a group of rare autoimmune diseases which caused inflammation, damage, and destruction to small blood vessels. These conditions can affect various organs in your body. The major types of ANCA-associated vasculitis are granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. However, avacopan received Orphan Drug and Orphan Medicinal Product designations for the treatment of granulomatosis with polyangiitis, microscopic polyangiitis, and a separate condition called C3 glomerulopathy. We will explain the differences below between the two forms of ANCA-associated vasculitis, and C3.

Granulomatosis with Polyangiitis

Formerly known as Wegener’s granulomatosis, granulomatosis with polyangiitis (GPA) is a rare and serious disease affecting blood vessels. Caused by tissue damage and a lack of cellular oxygenation, the blood vessels become swollen throughout the body. As a result, blood flow is inhibited. Further, cells are continuously deprived of oxygen. GPA impacts multiple parts of the body, from the sinuses and kidneys to the lungs, ears, eyes, skin, joints, and nerves. Symptom development is progressive and includes:

• Shortness of breath or difficulty breathing
• Frequent and severe nosebleeds
• Fatigue
• Rashes
• Congestion
• Changes in hearing
• Fever and night sweats
• Coughing up blood
• Joint pain and sensitivity

Without treatment, GPA can cause organ failure. As a result, patients suspecting a problem should visit a doctor as soon as possible. Learn more about GPA.

C3 Glomerulopathy

There are two main forms of C3 glomerulopathy, a group of progressive conditions which impact the kidneys. The first is C3 glomerulonephritis and the other is dense deposit disease. In many cases, CFH, C3, or CFHR5 gene mutations cause C3 glomerulopathy. These mutations overactive that complement system, causing glomeruli damage. Symptoms include bloody urine, lower urine amounts, proteinuria (excess protein in the urine), and low blood proteins. Generally, patients with C3 glomerulopathy will reach renal disease within 10 years.

Learn more about C3 glomerulopathy.

Microscopic Polyangiitis

Doctors are not sure what causes microscopic polyangiitis (MPA), though many suspect it relates to the immune system. This rare condition is characterized by vasculitis (swollen blood vessels), generally in the skin, joints, kidneys, lungs, and nervous system. In patients with MPA, the blood vessels become narrow and weak. As a result, they can rupture or inhibit blood flow. Without treatment, MPA can cause aneurysms and organ failure. An estimated 3 out of every 100,000 people has MPA.

Symptoms vary. However, they include:

• Unintended weight loss
• Loss of appetite
• Fever
• Fatigue
• Bloody urine
• Joint and muscle pain
• Swelling of the lower extremities
• Skin rashes
• Coughing up blood
• Shortness of breath
• Nerve damage
• Respiratory distress
• Kidney failure

Learn more about MPA.