On-Pump Cardiothoracic Surgery (DX-88)

ACE Inhibitor: Class of medicines used to treat high blood pressure and other diseases.
Anabolic steroid: Also referred to as attenuated androgen, a class of steroid hormones used to prevent HAE attacks. Although their mechanism of action in HAE patients is unknown, these agents are believed to partially reverse the biochemical defect by increasing levels of C1-esterase inhibitor (C1-INH), helping to prevent angioedema attacks in patients with inherited C1-INH deficiency.
Antifibrolytic agent: Medicines used to prevent HAE attacks. These agents inhibit the activation of plasmin, a chemical in the blood that can make the C1-INH less effective.
Attenuated androgen: Also referred to as anabolic steroid, a class of steroid hormones used to prevent HAE attacks. Although their mechanism of action in HAE patients is unknown, these agents are believed to partially reverse the biochemical defect by increasing levels of C1-esterase inhibitor (C1-INH), helping to prevent angioedema attacks in patients with inherited C1-INH deficiency.
Bradykinin: A protein that causes blood vessels to expand (dilate) and leak serum and other fluids.
C1 inhibitor: Also referred to as C1-INH, a protein found in the fluid part of your blood that controls C1, a component of your body’s complement system. Abnormal swelling can result when C1-INH is insufficient or defective.
C1-INH: Also referred to as C1 inhibitor, a protein found in the fluid part of your blood that controls C1, a component of your body’s complement system. Abnormal swelling can result when C1-INH is insufficient or defective.
Complement system: The complement system is made up of proteins like C1 that float in your bloodstream, which work with the immune system to fight organisms like bacteria, viruses and parasites.
Drug formulary: A list of prescription medications selected for coverage under a health insurance plan.
HAE: HAE, or Hereditary Angioedema, is a rare, hereditary disease of the immune system that affects an estimated 1 in 10,000 to 1 in 50,000 adults and children globally. HAE causes attacks of spontaneous swelling that are often painful and severe, and can be life-threatening.
Hereditary Angioedema: A rare, hereditary disease of the immune system that affects an estimated 1 in 10,000 to 1 in 50,000 adults and children globally. Hereditary Angioedema (HAE) causes attacks of spontaneous swelling that are often painful and severe, and can be life-threatening.
Laryngeal attack: An HAE attack that affects the larynx (throat); this can block or close the airway, leading to difficulty breathing and, potentially, death.
Plasma kallikrein: A chemical in the bloodstream that is involved in blood clotting; it plays an important role in causing the swelling of HAE attacks.
Preventive therapy: In HAE, medicine taken to prevent attacks.
Prodrome: One or more physical warnings of an HAE attack; can appear as a rash or a feeling of skin tightness.
Serum: The clear, watery, fluid-component of blood that resembles fluid in a blister.
Subcutaneous: Beneath the skin.
Trigger: In HAE, something that causes an attack. Stress and trauma are two common HAE attack triggers.

DX-88 (CB-500,929) to Reduce Blood Loss in Cardiac Surgery

What is On-Pump Cardiothoracic Surgery (CTS)?

Each year in the U.S., more than 500,000 patients undergo on-pump cardiothoracic surgery (CTS), which includes coronary artery bypass grafting (CABG) and heart valve replacement or repair procedures, to repair blocked arteries that cannot be opened with stents or other less invasive procedures.

In on-pump CTS procedures, the heart is stopped, and blood is rerouted through a separate cardiopulmonary bypass (CPB) machine. The heart is filled with a solution to keep it still. Throughout the procedure, the pump takes over the function of the heart and lungs and supplies oxygenated blood to the body. Following placement of the grafts, blood flow is restored and the heart restarted.

One of the inherent risks of this surgery is contact activation of the inflammatory cascade. When a patient's blood comes into contact with the artificial surface of the CPB machine and tubing, serious complications can result, including blood loss and systemic inflammatory response syndrome (SIRS), a whole body inflammatory state that compromises heart and lung function in already fragile patients.

Why DX-88 (CB-500,929) in On-Pump CTS?

Typical on-pump surgical procedures trigger activation of the enzyme plasma kallikrein, resulting in blood loss and systemic inflammatory responses. DX-88 is a small protein with high affinity and specificity for plasma kallikrein, a key enzyme in the inflammatory cascade that is thought to be a relevant target during on-pump CTS. Plasma kallikrein liberates bradykinin, a molecule that causes local leakage of fluid from the blood vessels into the tissues.

Current treatments for patients undergoing complicated CABG procedures have been shown to be either less efficacious in reducing blood loss or pose significant safety risks. As a specific inhibitor of plasma kallikrein, DX-88 may offer an alternative therapy to help reduce blood transfusion needs associated with on-pump CTS and possibly decrease systemic inflammatory effects.

Clinical Trial Status

In April 2008, Dyax licensed to Cubist Pharmaceuticals DX-88 for the prevention of blood loss during surgery with rights to North America and Europe. Cubist is responsible for the ongoing development of DX-88 for intravenous administration in this indication. For more information about this indication please visit Cubist.

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Dyax - Advancing Novel Biotherapeutics

DX-88 (CB-500,929) to Reduce Blood Loss in Cardiac Surgery

What is On-Pump Cardiothoracic Surgery (CTS)?

Why DX-88 (CB-500,929) in On-Pump CTS?

Clinical Trial Status