Source: CSL Behring

Source: CSL Behring

Over fifty therapeutic plasma proteins are commercially available, and new ones are being evaluated for therapeutic use. Furthermore, the industry seeks new clinical uses for existing proteins. Many of the diseases treated with plasma proteins are rare – affecting relatively few patients. Consequently, many of these proteins are classified as orphan drugs. There are four main categories of plasma-based products:

  1. Immune globulins (IgG) are produced by B-cells in the body to identify and help destroy foreign molecules, including bacteria and viruses. They are the main function of the body’s humoral immune system. Replacement therapy with immune globulins has been used extensively since their commercial introduction in the 1950’s. Two categories of immunoglobulin preparations exist today:
    1. Polyvalent intravenous and subcutaneous immunoglobulins (IVIG/SCIG), or IgGare the most common preparations, consisting in millions of antibodies (immunoglobulins) concentrated into a vial capable of fighting a multitude of bacterial and viral infections, as well as diseases in other areas, including autoimmune disorders, hematology, infectious diseases, immuno-compromised cancer patients, some neurological conditions, etc. Polyvalent IgG was first prescribed as an antibody replacement therapy for congenital immuno-deficiencies through the intramuscular route, and subsequently intravenously and subcutaneously. Later on, IgG was also found to be also efficacious as a result of its immuno-modulatory effects on the human body. In this mode of action, it is prescribed for treating various neurological and autoimmune conditions. Well over 200 diseases have been identified for IgG treatment, many of them affecting only a small number of patients.
       
      The indications approved by the FDA and other regulatory agencies include: Primary Immunodeficiencies (PID), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Idiopathic Thrombocytopenic Purpura (ITP), Multifocal Motor Neuropathy (MMN), Kawasaki Disease, Chronic Lymphocytic Leukemia (CLL) and Bone Marrow Transplant (BMT).
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    3. Hyperimmune immunoglobulinsare preparations in which the level of some specific antibodies has been enriched to target a particular antigen, as opposed to the naturally diverse set of antibodies present in IgG. Specific hyperimmune preparations are manufactured for such conditions as Anti-D (anti-RhoD), Cytomegalovirus (CMV), Hepatitis A and B, Rabies, Tetanus, Varicella, etc. Some rare products target anthrax or other viruses for bio-defense purposes. Attempts to develop an anti-HIV immune globulin failed due to manufacturing difficulties, and are no longer pursued because of the efficacy of the currently available anti-HIV immunotherapies.
  2. Coagulation factors or clotting factors, such as factor VIII and IX are proteins involved in the human body’s “coagulation cascade” – the whole process of controlling blood clotting.Congenital hemophilia is the result of a missing or dysfunctional factor protein in the coagulation cascade. A person with hemophilia is often unable to control a bleeding situation and requires “replacement therapy” for the missing clotting protein.
    1. Hemophilia A: Factor VIII deficiency causes hemophilia A, and can be mild, moderate or severe. Many moderate and severe patients need factor VIII replacement therapy either on a regular basis (prophylaxis) or in the event of a bleeding episode (on-demand)
    2. Hemophilia B: Factor IX deficiency causes hemophilia B, and like hemophilia A, it may be mild, moderate or severe, although it is not as prevalent as hemophilia A worldwide: the ratio is roughly 5:1 hemophilia A to hemophilia B. Hemophilia B requires factor IX replacement therapy. Hemophilia A and B affect males at much higher rates than females because it is an X-linked chromosomal disease.
    3. Von Willebrand Disease (vWD): Von Willebrand Disease is caused by the lack or dysfunction of the von Willebrand Factor (vWF), which binds with factor VIII to promote blood clotting. This disease is more prevalent than hemophilia, but a greater percentage of patients are mild and need little treatment. Severe patients often require the use of a product containing vWF, which generally also contains factor VIII. vWD equally affects males and females.
    4. Other Factor Deficiencies: There are several other factor deficiencies, some of which are acquired during surgery or blood loss situations, while others are congenital. These include deficiencies of factors II, V, VII, X, XI, XIII and fibrinogen (FI).

 

  1. Albuminhas been used since the 1940’s as a volume replacement therapy for blood or fluid loss in surgery or trauma situations. It is also used in cirrhotic patients, those with liver diseases, sepsis, septic shock, therapeutic plasma exchange, burn therapy and renal dialysis, among others. In some of these conditions, albumin competes with non-protein based volume replacement solutions such as starches, Ringer’s Lactate or saline.
  2. Alpha-1 antitrypsin (AAT) or Alpha-1 Proteinase Inhibitor (A1PI)is used as a replacement therapy for A1PI deficiency, which is a rare genetic disorder characterized by reduced serum levels of the A1PI enzyme. It causes a variety of conditions including emphysema, chronic obstructive pulmonary disease (COPD), bronchiectasis, chronic bronchitis, cirrhosis, neonatal hepatitis and jaundice. Alpha-1 antitrypsin deficiency is found mainly among people of northern European descent, and it is less common in other populations, and practically non-existent in Asia.
  3. Albumin

    Antithrombin III (AT-III)is used as a replacement therapy for AT-III deficiency, which results in the inability to adequately control the clotting process, leading to excessive clotting and risk of thrombosis. The congenital deficiency is rare, but the acquired form can develop from liver dysfunction, sepsis, etc. and major surgery. AT-III can be used before, during or after surgery as an anticoagulant for patients suffering from low AT-III protein levels.

  4. C1 Esterase Inhibitor (C1-INH)is used as a replacement therapy for Hereditary Angioedema (HAE), which results in the swelling of the face, neck, extremities and upper airways. If left unchecked, this rare disease causes swelling of the larynx, which can lead to suffocation. C1-INH therapy replaces the missing protein in this congenital disease.