Catridecacog: First drug to treat rare genetic blood clotting disorder

New Drug

Catridecacog, or coagulation factor XIII A-subunit, recombinant (Tretten—Novo Nordisk), a minimally invasive option for treating rare congenital factor XIII A-subunit deficiency, has received FDA approval.

According to Novo Nordisk, catridecacog helps to prevent bleeding in children and adults who have the coagulation factor XIII A-subunit deficiency, an extremely rare genetic disorder. Catridecacog is the first drug to receive FDA approval for this indication. FDA also granted catridecacog orphan drug status because it treats a rare disease.

Pathophysiology of the disorder 

Factor XIII is a terminal enzyme in the blood coagulation cascade that stimulates cross-linking of fibrin and other proteins in the fibrin clot to promote hemostasis. In human plasma, factor XIII circulates as a heterotetramer of two functional subunit proteins—two factor XIII A-subunits and two factor XIII B-subunits. The factor XIII A-subunit acts as the enzyme, while factor XIII B-subunit acts as a carrier for the factor XIII A-subunit. 

During coagulation, the factor XIII is activated by thrombin and calcium; the factor XIII A-subunit dissociates from the factor XIII B-subunit to become active and help cross-link fibrin to enhance platelet and clot adhesion to injured tissue. 

Patients with the factor XIII A-subunit deficiency have a significantly lower level of the active subunit, thus resulting in less stable clotting for injured tissue. Catridecacog binds to the free human factor XIII B-subunit, as factor XIII A-subunit, to strengthen fibrin clots, impede fibinolysis, and enhance platelet adhesion to the injury site.

Safety and efficacy

During clinical development, researchers studied the effectiveness of catridecacog in 77 patients with coagulation factor XIII A-subunit deficiency. Catridecacog was effective in preventing bleeding in 90% of the patients when given the recommended dose of 35 IU/kg. The mean age of study participants was approximately 26 years (63.4% > 18 years), and the male to female ratio was 3:2. The most common related adverse events (occurring in >1% of patients treated with catridecacog) were headache, pain in the extremities, injection site pain, and an increase in nonneutralizing antibodies.

Warnings and precautions

Use of catridecacog is contraindicated in patients who have known hypersensitivity to the active substance or to any of the excipients. Because increased levels of rFXIII may increase the risk of thrombosis, health professionals should exercise caution in patients with a predisposition to conditions of thrombosis. Incorrect storage of the product after reconstitution may result in loss of sterility and increased levels of activated rFXIII.

Catridecacog, coagulation factor XIII A-subunit, recombinant (Tretten)

Manufacturer: Novo Nordisk

Drug class: Blood coagulation factors

Indication: Treatment of congenital factor XIII A-subunit deficiency

Dosage: 35 IU/kg once monthly 

To administer, reconstitute with sterile water for injection with a 10-mL syringe.

A dose recommendation cannot be made for older adults, pregnant patients, or children younger than age 6 years due to lack of data.

Of note: Treatment should be initiated under the supervision of a physician experienced in the treatment of rare bleeding disorders. Do not use vial if solid matter and discoloration are present in the reconstituted product. Administer at a rate not exceeding 1–2 mL per minute. Do not administer as a drip or with other infusion solutions.

Patient counseling

Give patients the Medication Guide and review it with them carefully. Verify the diagnosis, since catridecacog should not be used for prophylactic treatment of bleeding in patients with congenital factor XIII B-subunit deficiency. Advise patients that breakthrough bleeding may be a sign and symptom of inhibitor formation, and they may have to see their health care provider to measure antibody concentrations. Tell patients to inform their health care provider of all the medications they may be taking.