POLICY INACTIVATED September 5, 2022.

Acquired (immune) thrombotic thrombocytopenic purpura (aTTP) is a rare thrombotic microangiopathy that is characterized by thrombocytopenia and hemolytic anemia. In this condition, autoantibodies inhibit activity of the von Willebrand factor-attaching protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which leads to abnormal blood clotting throughout the body. As a result, tissue ischemia and multiorgan dysfunction may occur leading to thromboembolic events and death. Treatment consists of plasma exchange, to replenish functional ADAMTS13 and remove von Willebrand factor and autoantibodies; and immunosuppressive therapy (e.g. glucocorticoids and rituximab) to suppress anti-ADAMTS13 autoantibodies.

The U.S. Food and Drug Administration (FDA) has approved intravenous and subcutaneous use of caplacizumab (Cablivi^®) for treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy. Caplacizumab is a humanized antibody fragment that targets von Willebrand factor (vWF), preventing interaction between vWF and platelets, thereby reducing abnormal platelet and clotting activity. The first dose should be administered by a healthcare provider as a bolus intravenous injection. Subsequent doses are administered subcutaneously and may be given by patients or caregivers after proper training.

Caplacizumab is contraindicated in patients with previous severe hypersensitivity reactions to caplacizumab or any of the inactive substances found in caplacizumab (Cablivi^®). Severe bleeding can occur, especially in patients with underlying coagulopathies. 

I.    Initial Review for Cablacizumab (Cablivi®)

Caplacizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Age 18 years or older; AND
• Diagnosis of acquired (immune) thrombotic thrombocytopenic purpura (aTTP) confirmed by ONE of the following:
  • Clinical presentation of aTTP defined as BOTH of the following;
    1. Thrombocytopenia; and
    2. Microangiopathic hemolytic anemia with schistocytes (red blood cell fragments) seen on blood smear; OR
  • ADAMTS13 activity level of less than 10%; AND
• Used in combination with BOTH of the following;
  • Plasma exchange therapy; and
  • Immunosuppressive therapy (e.g. rituximab, glucocorticoids); AND
• Prescribed by or in consultation with a specialist (e.g., hematologist); AND
• No FDA labeled contraindications to caplacizumab (see table 1 below); AND
• Requested dose is within the FDA labeled dose for the indication (see table 2 below).

II.    Renewal Review for Cablacizumab (Cablivi®)

Caplacizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for caplacizumab through the initial review process; AND
• Demonstrated positive clinical response to therapy with caplacizumab (e.g., increased ADAMTS13 activity); AND
• Used in combination with BOTH of the following:
  • Plasma exchange therapy; and
  • Immunosuppressive therapy (e.g. rituximab, glucocorticoids); AND
• No FDA labeled contraindications to caplacizumab (see table 1 below); AND
• Requested dose is within the FDA labeled dose for the indication (see table 2 below).

III.   Experimental/Investigative Uses

All other uses of caplacizumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1. FDA Labeled Contraindications

Table 2. Dosing 

Documentation Submission:
NOTE: See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table.

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing clinical signs and symptoms of disease.
2. Laboratory results confirming the diagnosis aTTP.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (frequency) associated with inadequate response.

Renewal Review

1. Documentation of prior approval for caplacizumab through the initial review process.
2. Documentation supporting positive clinical response including any recurrences of aTTP.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (frequency) associated with inadequate response.