For U.S. Healthcare Professionals Only
For U.S. Healthcare Professionals Only

CABLIVI is the first and only therapy targeted to prevent microthrombi in adults with aTTP1,2

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

How CABLIVI works1,3,4

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 risk in aTTP is caused by platelet aggregation on ULvWF leading to microthrombi

Microthrombi inhibition with CABLIVI

CABLIVI blocks vWF-mediated platelet aggregation, inhibiting microthrombi formation

When bound to the A1 domain of vWF, CABLIVI inhibits the interaction between vWF and platelets When bound to the A1 domain of vWF, CABLIVI inhibits the interaction between vWF and platelets

CABLIVI MOA: The first of its kind

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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.

INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS:

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.

CONTRAINDICATIONS:

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.

WARNINGS AND PRECAUTIONS:

Bleeding Risk:
  • •CABLIVI increases the risk of bleeding. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of subjects. Overall, bleeding events occurred in approximately 58% of patients on CABLIVI versus 43% of patients on placebo. The risk of bleeding is increased, in patients with underlying coagulopathies and concomitant use of CABLIVI with drugs affecting hemostasis.
  • •If clinically significant bleeding occurs, interrupt use of CABLIVI. Von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If CABLIVI is restarted, monitor closely for signs of bleeding.
  • •Withhold CABLIVI for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and CABLIVI is resumed, monitor closely for signs of bleeding.

ADVERSE REACTIONS:

The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).

CONCOMITANT USE OF ANTICOAGULANTS:

Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.

PREGNANCY:

There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

  • •Fetal/neonatal adverse reactions: CABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.
  • •Maternal adverse reactions: All patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnant women receiving CABLIVI should be carefully monitored for evidence of excessive bleeding.

Please see accompanying full Prescribing Information.

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aTTP=acquired thrombotic thrombocytopenic purpura; vWF=von Willebrand factor.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS:

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.

WARNINGS AND PRECAUTIONS:

Bleeding Risk:

  • CABLIVI increases the risk of bleeding. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of subjects. Overall, bleeding events occurred in approximately 58% of patients on CABLIVI versus 43% of patients on placebo. The risk of bleeding is increased, in patients with underlying coagulopathies and concomitant use of CABLIVI with drugs affecting hemostasis.
  • If clinically significant bleeding occurs, interrupt use of CABLIVI. Von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If CABLIVI is restarted, monitor closely for signs of bleeding.
  • Withhold CABLIVI for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and CABLIVI is resumed, monitor closely for signs of bleeding.

ADVERSE REACTIONS:

The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).

CONCOMITANT USE OF ANTICOAGULANTS:

Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.

PREGNANCY:

There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

  • Fetal/neonatal adverse reactions: CABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.
  • Maternal adverse reactions: All patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnant women receiving CABLIVI should be carefully monitored for evidence of excessive bleeding.

INDICATIONS:

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.

References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
References:
  1. 1. Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre. Am J Hematol. 2017;92(4):381-387.
  2. 2. Scully M, Hunt BJ, Benjamin S, et al; on behalf of British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335.
  3. 3. Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: national representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458.
  4. 4. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017;15(7):1448-1452.
  5. 5. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  3. 3. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3:17020. doi:10.1038/nrdp.2017.20
  4. 4. Holz J-B. The TITAN trial—assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012;46(3):343-346.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  3. 3. Supplement to: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  4. 4. Protocol for: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
Reference:
  1. 1. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
Reference:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. CABLIVI [instructions for use]. Cambridge, MA: Genzyme Corporation; 2019.
References:
  1. 1. Centers for Medicare & Medicaid Services. Draft ICD-10-CM/PCS MS-DRGv28 Definitions Manual: MDC 8 Diseases & Disorders of the Musculoskeletal System & Connective Tissue Disorders. https://www.cms.gov/icd10manual/fullcode_cms/P0209.html. Accessed July 25, 2019.
  2. 2. Centers for Medicare & Medicaid Services. Department of Health and Human Services. 42 CFR §412, 413, 495. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Proposed Policy Changes and Fiscal Year 2020 Rates; Proposed Quality Reporting Requirements for Specific Providers; Medicare and Medicaid Promoting Interoperability Programs Proposed Requirements for Eligible Hospitals and Critical Access Hospitals. Fed Regist. 2019;84:19158-19677.
  3. 3. Data on file. Conshohocken, PA: Sanofi; 2018.
  4. 4. Centers for Medicare & Medicaid Services. 2019 ICD-10-CM. https://www.cms.gov/Medicare/Coding/ICD10/2019-ICD-10-CM.html. Updated June 20, 2019. Accessed July 23, 2019.
  5. 5. Centers for Medicare & Medicaid Services. 2020 ICD-10-PCS. https://www.cms.gov/Medicare/Coding/ICD10/2020-ICD-10-PCS.html. Accessed July 25, 2019.

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SAUS.CAPL.19.07.3919b(1) December 2019