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Biologics Will Pump Up the Vasculitis Market

Chris Fellner

Vasculitis (also known as angiitis and arteritis) is a group of heterogeneous disorders characterized by inflammation and necrosis of the blood vessels, including the veins, arteries, and capillaries. Several forms of vasculitis exist, and their clinical characteristics can differ substantially in terms of symptoms, severity, and duration of disease, depending on the organs and the types of blood vessels that are involved.13 The exact cause of vasculitis remains unknown, but factors that appear to trigger the disease include an individual’s genetic makeup, infections (such as hepatitis B and C), blood cancers, immune system diseases (such as rheumatoid arthritis and scleroderma), and reactions to certain drugs.2

The various types of vasculitis are grouped according to the size of the blood vessels they affect. Large-vessel vasculitis includes Behçet’s disease, Takayasu’s arteritis, giant cell arteritis (also known as temporal arteritis), and polymyalgia rheumatica; vasculitis affecting medium-size vessels includes Kawasaki’s disease, polyarteritis nodosa, and Buerger’s disease (thromboangiitis obliterans); and small-vessel vasculitis includes immunoglobulin A vasculitis, cryoglobulinemia vasculitis, and hypersensitivity vasculitis. The various types of vasculitic disease are listed in Table 1.1

The main goal of treating vasculitis is to reduce inflammation in the affected blood vessels. The prescription medications most commonly used to treat vasculitis include corticosteroids (such as prednisone, prednisolone, and methylprednisolone) and cytotoxic drugs (such as azathioprine, methotrexate, and cyclophosphamide). Corticosteroids help to reduce inflammation in blood vessels, and cytotoxic medications kill the immune-system cells that cause inflammation.1,5 All of these drugs, however, are used off-label in patients with vasculitis.4

In April 2011, the biologic therapy rituximab (Rituxan, Biogen Idec/Genentech) became the first and only FDA-approved treatment for vasculitis. Specifically, rituximab is indicated in combination with glucocorticoids for patients with Wegener’s granulomatosis (a rare disorder that causes vasculitis) or microscopic polyangiitis (a type of vasculitis affecting the small blood vessels).6 Rituximab is a genetically engineered chimeric murine/human monoclonal immunoglobulin G1 (IgG1) kappa antibody directed against CD20 antigens expressed on the surface of pre-B and mature B lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis.7

Table 2 lists the leading vasculitis treatments in use in the United States.4 On the horizon, six biologics are in late-stage development as potential vasculitis therapies (Table 3). All offer novel mechanisms of action.4

Abatacept (Orencia, Bristol-Myers Squibb/Ono Pharmaceuticals) is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) linked to the modified Fc portion of human IgG1. It is approved in the U.S. for the treatment of adult rheumatoid arthritis and juvenile idiopathic arthritis.8,9 In addition, the drug is in phase 3 development globally for granulomatosis with polyangiitis (GPA) and in phase 2 development for large-vessel vasculitis and Behçet’s disease.4

Apremilast (Otezla, Celgene) is an oral, small-molecule phosphodiesterase 4 (PDE4) inhibitor indicated for the treatment of psoriatic arthritis and psoriasis.10 By inhibiting PDE4, apremilast increases intracellular levels of cyclic adenosine monophosphate, which in turn modulates the expression of inflammatory cytokines.10,11 It is the only drug in late-stage development for the treatment of Behçet’s disease and the only oral formulation under development in the vasculitis pipeline.4

Belimumab (Benlysta, GlaxoSmith-Kline) is a human IgG1 gamma monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred to as B-cell activating factor). By binding BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. It is indicated for use in adults with active, autoantibody-positive, systemic lupus erythematosus.12 Belimumab is the only drug in late-stage development for microscopic polyangiitis. It is also under development for GPA.4

Infliximab (Remicade, Janssen Biotech) is a chimeric IgG1 kappa monoclonal antibody specific for human tumor necrosis factor (TNF)-alpha. It neutralizes the biologic activity of TNF-alpha by binding with high affinity to the soluble and transmembrane forms of TNF-alpha and inhibits binding of TNF-alpha with its receptors. TNF-alpha induces proinflammatory cytokines, such as interleukin (IL)-1 and IL-6; enhances leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes; activates neutrophil and eosinophil functional activity; and induces acute-phase reactants and other liver proteins, as well as tissue-degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab is in phase 3 clinical development for the treatment of Kawasaki’s disease in the U.S.4

Mepolizumab (Nucala, GlaxoSmith-Kline) is a humanized IL-5 antagonist monoclonal antibody produced by recombinant DNA technology. IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils in inflammation. Mepolizumab is being developed as a treatment for eosinophilic GPA (eGPA, also known as Churg-Strauss syndrome) and, if approved, would be the only drug with that indication in the vasculitis arena. It is the most expensive pipeline biologic, with an expected treatment cost of approximately $71,600 in the U.S. (see Table 3).4

Tocilizumab (Actemra, Genentech/Roche) is a recombinant humanized anti-human IL-6 receptor monoclonal antibody of the IgG1 kappa subclass. IL-6 is a proinflammatory cytokine produced by a variety of cell types, including T and B cells, lymphocytes, monocytes, and fibroblasts. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors and has been shown to inhibit IL-6–mediated signaling through those receptors. Tocilizumab is the only drug in late-stage development for large-vessel vasculitis (i.e., giant cell arteritis and Takayasu’s arteritis).4

The vasculitis market in the U.S. is expected to grow at an annual rate of 3.8% during the decade between 2014 and 2024, reaching sales of $316 million. Key drivers of market growth will include the launch of mepolizumab for eGPA in 2018; the launch of tocilizumab for large-vessel vasculitis in 2019; and the launch of abatacept for microscopic polyangiitis and GPA in 2020 (see Table 3). At the same time, the launch of biosimilars (adalimumab in 2016, rituximab and infliximab in 2018, abatacept and tocilizumab in 2019, and belimumab in 2023) will cut into the sales of major brands.4


Types of Vasculitis1

Primary Blood Vessel Involvement
Large Vessels Medium Vessels Small Vessels
  • Behçet’s disease
  • Cogan’s syndrome
  • Giant cell arteritis (temporal arteritis)
  • Polymyalgia rheumatica
  • Takayasu’s arteritis (aortic arch syndrome)
  • Buerger’s disease (thromboangiitis)
  • Central nervous system vasculitis
  • Kawasaki’s disease (mucocutaneous lymph node disease)
  • Polyarteritis nodosa
  • Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis)
  • Cryoglobulinemia vasculitis
  • Immunoglobulin A vasculitis
  • Hypersensitivity vasculitis (allergic vasculitis, cutaneous vasculitis, leukocytoclastic vasculitis)
  • Microscopic polyangiitis

Leading Treatments for Vasculitis in the U.S. (2015)4

Drug Name Brands Therapeutic Class Indication(s)
Imuran, Imurel, generics
Immunosuppressive antimetabolite Vasculitis
Endoxan, Cytoxan, generics
Alkylating agent Vasculitis
Immunoglobulin (IV)
Numerous brands, including Privigen, Kiovig, Gammagard
IgG human antibody KD, LVV
Numerous generics
Folic acid analog; anti-neoplastic/antimetabolite Vasculitis
Mycophenolate mofetil
CellCept, Myfortic, generics
IMPDH inhibitor Vasculitis
Prednisone, prednisolone, methylprednisolone
Numerous generics
Glucocorticoids Vasculitis
Rituxan (Biogen Idec/Genentech)
CD-20 protein inhibitor MPA, WG

*Only rituximab is approved by the Food and Drug Administration for the treatment of patients with vasculitis.

IgG = immunoglobulin G; IMPDH = inosine monophosphate dehydrogenase; IV = intravenous; KD = Kawasaki’s disease; LVV = large-vessel vasculitis; MPA = microscopic polyangiitis; WG = Wegener’s granulomatosis.

Late-Stage Vasculitis Pipeline as of December 20154

Product Name Company Therapeutic Class Targeted Indication(s) Developmental Stage(s) Expected U.S. Treatment Cost Expected U.S. Launch Date
Abatacept (Orencia)
Bristol-Myers Squibb/Ono Pharmaceuticals
Selective co-stimulating modulator (inhibits T cell activation) BD, GPA, MPA Phase 2 (BD)
Phase 3 (GPA)
$41,642 2020 (GPA)
Apremilast (Otezla)
PDE4 inhibitor BD Phase 3 $6,220 2018
Belimumab (Benlysta)
BLyS-specific inhibitor GPA, MPA Phase 3 $50,190 2018 (GPA, MPA)
Infliximab (Remicade)
Janssen Biotech
TNF inhibitor KD Phase 3 $17,180 2016
Mepolizumab (Nucala)
IL-5 antagonist eGPA Phase 3 $71,617 2018
Tocilizumab (Actemra)
Anti–IL-6 monoclonal antibody GCA, TA Phase 3 $19,728 2019 (LVV)

Abatacept is expected to be used off-label for MPA.

BD = Behçet’s disease; BLyS = B lymphocyte stimulator; eGPA = eosinophilic granulomatosis with polyangiitis; GCA = giant cell arteritis; GPA = granulomatosis with polyangiitis; IL-1 = interleukin 1 family; IL-5 = interleukin 5 family; IL-6 = interleukin 6 family; IL-6R = interleukin 6 receptor; KD = Kawasaki’s disease; LVV = large-vessel vasculitis; MPA = microscopic polyangiitis; PDE4 = phosphodiesterase 4; TA = Takayasu’s arteritis; TNF = tumor necrosis factor.

Author bio: 
Chris Fellner is a medical writer and the Editor of


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