ISTH Guidelines

SEE aTTP^† — Diagnosis determined through clinical assessment

START CABLIVI^* — Consider early administration of CABLIVI in combination with PEX and immunosuppressive therapy

SUPPORT WITH ADAMTS13 — ADAMTS13 test results inform treatment decisions

ISTH TTP Guidelines are the first evidence-based, international
guidelines on the diagnosis, treatment, and management of aTTP^1,2

Treatment recommendations have evolved to include PEX, immunosuppressive therapy, and CABLIVI

Initiation of CABLIVI is recommended for acute aTTP events(initial and relapsing)

Starting CABLIVI early is believed to have the greatest benefit in the early phase of acute aTTP events (initial or relapsing)

Who should not start CABLIVI?

• CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients

• Withhold CABLIVI treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

*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. If ADAMTS13 testing is not available, do not add CABLIVI.
^†The ISTH TTP Guidelines refer to aTTP as iTTP.

INDICATIONS:
Cablivi is indicated for the treatment of adults and adolescents of 12 years of age and older weighing at least 40 kg experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression

IMPORTANT SAFETY INFORMATION 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.

aTTP=acquired thrombotic thrombocytopenic purpura; ISTH=International Society on Thrombosis and Haemostasis;
iTTP=immune thrombotic thrombocytopenic purpura; PEX=plasma exchange; TTP=thrombotic thrombocytopenic purpura.

See aTTP—Diagnosis determined through clinical assessment¹
aTTP is a life-threatening blood disorder with considerable morbidity and mortality in the acute phase

Diagnose aTTP through clinical assessment or risk assessment tools prior to ADAMTS13 testing

Clinical assessment^†

Thrombocytopenia (<150 × 109/L)
Evidence of microangiopathic hemolytic anemia

– Hb and hematocrit below reference range
– Low haptoglobin
– Presence of schistocytes in peripheral blood smear

Relatively preserved renal function

OR

Risk assessment tools^†

Available risk assessment tools include:

PLASMIC score
French score

The higher the risk assessment score the more likely patients have severe ADAMTS13 deficiency and aTTP

Identifying aTTP is crucial for initiation of an appropriate therapeutic strategy

^*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. If ADAMTS13 testing is not available, do not add CABLIVI.
^†List includes laboratory tests and results only; exclusive of physical symptoms, such as petechiae.
^‡ISTH did not appraise the evidence of these 2 tools.

IMPORTANT SAFETY INFORMATION (cont’d) WARNINGS AND PRECAUTIONS:

• CABLIVI increases the risk of bleeding. Cases of major bleeding, including life-threatening and fatal bleeding have been reported in patients receiving CABLIVI, mainly in those using concomitant anti-platelet agents or anticoagulants. The risk of bleeding is increased in patients with underlying coagulopathies and concomitant use of CABLIVI with drugs affecting hemostasis.
• 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.
• 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.

Hb=hemoglobin; LDH=lactate dehydrogenase.

Start CABLIVI^*—Consider early administration of CABLIVI in combination with PEX and immunosuppressive therapy¹
Recommended diagnostic and management strategy for acute events with access to ADAMTS13 results within 7 days

Treatment of relapses for a patient previously diagnosed with aTTP could be started safely based on clinical grounds without the need for a confirmatory ADAMTS13 test

Who should not start CABLIVI?

• CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients
• Withhold CABLIVI treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

IMPORTANT SAFETY INFORMATION (cont’d) 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.

Support with ADAMTS13—ADAMTS13 test results inform treatment decisions¹
Timely access to ADAMTS13 results is key to providing optimal care for patients with aTTP

Select US labs testing ADAMTS13 activity, inhibitors, and antibodies
ARUP Labs	800-522-2787
LabCorp	800-334-5161
Machaon Diagnostics	800-566-3462
Mayo Clinic Laboratories	800-533-1710
Quest Diagnostics	866-697-8378
Versiti	800-245-3117 x6250

These listings do not constitute an endorsement by Sanofi Genzyme and are not included in the ISTH Guidelines. The following is a selection of national laboratories offering ADAMTS13 tests activity, inhibitor, and antibody testing. This is not an exhaustive list of labs that offer one or more of these tests or an endorsement of any lab. Other testing options may be available, including at local or regional laboratories. Content is current as of July 2020, and tests may not be available in all states. Please call laboratory to confirm test availability, sample shipping information, and all other logistics.

Prescribe CABLIVI—the first and only FDA-approved, guideline-recommended therapy for aTTP in combination with PEX and immunosuppressive therapy

IMPORTANT SAFETY INFORMATION (cont’d) PREGNANCY:

• Pregnancy: There are no data on the use of caplacizumab in pregnant women. Studies in guinea pigs showed no effect of caplacizumab on the dams or foetuses. As a precautionary measure, it is preferable to avoid the use of Cablivi during pregnancy.
• Breastfeeding: There are no data on the use of caplacizumab in breastfeeding women. It is unknown whether caplacizumab is excreted in human milk. A risk to the child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to abstain/discontinue from therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;(jth.15006). doi:10.1111/jth.15006 2. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;(jth.15010). doi:10.1111/jth.15010

MAT-AE-2200643-V2-OCT-23

OR

References