Sanofi Promise Warranty Program for Cablivi® (caplacizumab-yhdp) Seeks to Help Support Physicians Managing aTTP


Acquired thrombotic thrombocytopenic purpura (aTTP is also known as iTTP) is a rare, life-threatening medical emergency that can cause microvascular thrombi and consequent thrombocytopenia, hemolytic anemia, and organ ischemia.1,2,3 In the US, aTTP affects fewer than 2,000 adults each year.4 The disease course of aTTP is unpredictable and can be rapidly fatal, making its diagnosis and management an urgent need.1,5-7

At Sanofi, we are committed to supporting the aTTP community and the health care providers who treat them. As part of this commitment, we have launched the Sanofi Promise Warranty Program for Cablivi with the goal of helping support health care providers prescribe with confidence.

Sanofi’s Commitment to the aTTP Community

With the Sanofi Promise Warranty Program for Cablivi, the cost of Cablivi will be refunded for up to six (6) inpatient doses for patients who fail to reach initial clinical response to Cablivi or up to twelve (12) inpatient doses for patients who exacerbate while on Cablivi treatment in the hospital setting (as defined by the program terms), for institutions who meet the Eligibility Requirements. The refund amount will be up to wholesale acquisition cost (WAC) or actual acquisition cost, whichever is less. Cablivi must be prescribed in accordance with the FDA-approved label (Prescribing Information below).

Cablivi was approved in 2019 as the first and only therapy for adults with aTTP, in combination with plasma exchange (PEX) and immunosuppressive therapy (IS).8,9 In the pivotal, phase 3, double-blind HERCULES trial, the efficacy and safety of Cablivi, PEX, and IS (n=72) compared to placebo, PEX, and IS (n=73) was investigated in adult patients for the duration of daily PEX and 30 days thereafter. Patients could receive extended treatment for up to 28 days if signs of underlying disease persisted, such as suppressed ADAMTS13 activity levels.8,9 The primary endpoint was time to platelet count normalization, defined as platelet count ≥150,000/uL with discontinuation of daily PEX 5 days thereafter.8,9  In combination with PEX and IS, Cablivi helped to normalize platelet counts faster than PEX and IS alone (HR (95% CI): 1.55 (1.10-2.20); p=0.01; median days 2.69 vs. 2.88 respectively), reduced potentially serious aTTP-related events (as measured by a composite endpoint of aTTP-related death, recurrence*, or ≥1 major thromboembolic event during the study drug period) by 74% (9 (12.7%) vs. 36 (49.3%), respectively; p<0.0001), and significantly reduced the number of recurrences requiring reinitiation of PEX by 67% (p<0.001).8

The safety of Cablivi was established in 106 patients across 2 studies. The most common adverse reactions, occurring in >15% of patients, were epistaxis (29%), headache (21%), and gingival bleeding (16%). Fifty-eight percent of patients in the Cablivi group experienced bleeding events compared to 43% of patients in the PEX and IS alone group. Severe bleeding was reported in 1% of patients for each of the following events: epistaxis, gingival bleeding, upper GI hemorrhage, and metrorrhagia.9

In addition to clinical data demonstrating the safety and efficacy of Cablivi, the International Society on Thrombosis and Haemostatis (ISTH) Guidelines – the first evidence-based, international guidance on the diagnosis, treatment, and management of aTTP – conditionally recommend early use of Cablivi± for initial or relapsing aTTP/iTTP. These Guidelines suggest that early administration of Cablivi in combination with PEX and IS should be considered after an aTTP diagnosis is determined through clinical assessment.

*Thrombocytopenia after initial recovery of platelet count (platelet count ≥150,000/μL) that required reinitiation of daily PEX was considered a recurrence. Recurrences were termed exacerbations if they occurred within 30 days of the last PEX and relapses if they occurred more than 30 days after the last PEX.

±A conditional recommendation defined as desirable effects of the recommendation probably outweighing the undesirable effects. Assumes timely access to ADAMTS13 testing and clinical diagnosis based on high likelihood of aTTP/iTTP. In de novo patients where no reasonable access to ADAMTS13 activity testing is available, the Guidelines do not recommend CABLIVI; however, treatment of a patient previously diagnosed with aTTP/iTTP could be safely undertaken on clinical grounds without the need for a confirmatory ADAMTS13 test. 

Addressing the Triple Threat of aTTP

Each aTTP episode can be unpredictable, with microthrombi-driven risks. aTTP presents similarly to a wide spectrum of clinical scenarios associated with thrombotic microangiopathies (TMA),10 which can make an accurate diagnosis challenging, both for patients and physicians.

The pathology of aTTP poses a triple threat:

  • The immune system creates autoantibodies directed against an individual’s own proteins.8
  • These autoantibodies inhibit ADAMTS13, an enzyme that normally prevents blood from clotting by cleaving the ultra-large von Willebrand factor (vWF) into smaller and less active forms.7,11
  • Uncleaved vWF (ULvWF) accumulates in plasma, leading to platelet aggregation and risk of microvascular thrombosis.11,12

PEX and IS directly address only some aspects of the disease. The triple threat of aTTP deserves a triple threat regimen with Cablivi, PEX, and IS in appropriate patients.

To learn more about Cablivi and the Sanofi Promise Warranty Program for Cablivi, please visit




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.



  • 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.
  • In the postmarketing setting cases of life-threatening and fatal bleeding were reported in patients receiving CABLIVI.
  • The risk of bleeding is increased in patients with underlying coagulopathies (e.g. hemophilia, other coagulation factor deficiencies). It is also increased with concomitant use of CABLIVI with drugs affecting hemostasis and coagulation.
  • Avoid concomitant use of CABLIVI with antiplatelet agents or anticoagulants. 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.


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


Concomitant use of CABLIVI with any anticoagulant or antiplatelet agent may increase the risk of bleeding. Avoid concomitant use when possible. 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.

  • 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.


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.

Please see Full Prescribing Information


1. Scully M, Hunt BJ, Benjamin S, et al; 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. doi:10.1111/j.1365-2141.2012.09167.x

2. Fodil S, Zafrani L. Severe Thrombotic Thrombocytopenic Purpura (TTP) with Organ Failure in Critically Ill Patients. Journal of Clinical Medicine. 2022; 11(4):1103.

3. Tsai H-M. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol. 2010;91(1):1-19. doi:10.1007/s12185-009-0476-1

4. Miller DP, Kaye JA, Shea K, et al. Incidence of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome. Epidemiology. 2004;15(2):208-215.

5. Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: nationally representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458. doi:10.1111/trf.13586 

6. Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500-1511. doi:10.1182/blood-2009-09-243790 

7. Akwaa F, Antun A, Cataland SR. How I treat immune-mediated thrombotic thrombocytopenic purpura after hospital discharge. Blood. 2022;140(5):438-444. doi:10.1182/blood.2021014514

8. 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.

9. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation.

10. Gallan AJ, Chang A. A new paradigm for renal thrombotic microangiopathy. Semin Diagn Pathol. 2020;37(3):121-126. doi:10.1053/j.semdp.2020.01.002

11. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857

12. 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. doi:10.1016/j.transci.2012.03.027 



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