For U.S. Healthcare Professionals Only
For U.S. Healthcare Professionals Only
In aTTP, a rare blood-clotting disorder, autoantibodies inhibit the activity of ADAMTS13, the specific von Willebrand factor–cleaving enzyme, resulting in unrestrained growth of ultra-large von Willebrand factor (ULvWF). These uncleaved ULvWF cause platelet adhesion and aggregation, leading to microthrombi formation.3
CABLIVI is a vWF-directed antibody fragment. Through its novel mechanism of action (MOA), CABLIVI targets the A1 domain of vWF and inhibits the interaction between vWF and platelets.
Microthrombi risk in aTTP
Caused by platelet aggregation on ULvWF leading to microthrombi
Microthrombi inhibition with CABLIVI
CABLIVI blocks vWF-mediated platelet aggregation, inhibiting microthrombi formation
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View Video Transcript
Acquired thrombotic thrombocytopenic purpura, or aTTP, is a rare, rapidly progressing, life-threatening autoimmune disease. Left untreated, up to 90% of aTTP patients die.
Historical treatment includes plasma exchange and immunosuppressive therapy, which has improved prognosis. However, despite these treatments, the mortality rate remains high at 8 to 20%. In a large retrospective study, the median time from diagnosis to death was 9 days despite treatment with plasma exchange.
Symptoms of aTTP can be complex and variable. Most common signs include thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia, resulting from microvascular occlusion. Clinical manifestations of organ ischemia can include strokes, transient ischemic attacks, myocardial infarction, and renal and mesenteric ischemia.
aTTP is caused by the severe deficiency of a von Willebrand factor–cleaving protease, ADAMTS13. This deficiency is due to formation of autoantibodies directed against ADAMTS13. Normally, ADAMTS13 breaks apart ultra large strings of von Willebrand factor, known as vWF, into smaller pieces. In aTTP patients, however, ADAMTS13 is blocked by autoantibodies, thereby greatly increasing the amount of ultra large vWF in circulation. Thousands of circulating platelets bind to these ultra large vWF strings, forming platelet-rich blood clots within small blood vessels throughout the body. These small clots are known as microthrombi.
As of February 2019, CABLIVI became the newest treatment approved by the FDA for aTTP in combination with plasma exchange and immunosuppressive therapy. Plasma exchange removes vWF and autoantibodies and replenishes ADAMTS13. Immunosuppressive therapies are intended to inhibit anti-ADAMTS13 autoantibody production. Neither directly affects the binding of platelets to vWF.
CABLIVI is a monoclonal antibody fragment that was developed to inhibit microthrombi formation in aTTP by binding specifically to the A1 domain of vWF. CABLIVI blocks the interaction between vWF and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption. This inhibits the formation of microthrombi while the underlying autoimmune disease is treated with immunosuppressive therapy.
CABLIVI (caplacizumab-yhdp) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have included urticaria.
The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).
Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.
There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.
Please see accompanying full Prescribing Information.
aTTP=acquired thrombotic thrombocytopenic purpura; vWF=von Willebrand factor.
CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have included urticaria.
Bleeding Risk:
The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).
Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.
There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.
CABLIVI (caplacizumab-yhdp) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
