Caplacizumab-yhdp (Mechanism of Action)

In this article, we will discuss Caplacizumab-yhdp (Mechanism of Action). So, let’s get started.

Mechanism of Action

Caplacizumab-yhdp targets the A1-domain of vWF, and inhibits the interaction between vWF  and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption.

Pharmacodynamics

Ristocetin cofactor (RICO) activity was used to assess vWF activity. Subcutaneous doses of caplacizumab-yhdp at greater than or equal to the approved recommended dosage to healthy subjects and patients with aTTP decreased RICO activity levels to below 20% approximately 4 hours post-dose. RICO activity returned to baseline values within 7 days of drug discontinuation.
Caplacizumab-yhdp decreased vWF antigen and factor VIII:C levels. These reductions were transient and returned to baseline upon cessation of treatment.

Pharmacokinetics

Caplacizumab-yhdp pharmacokinetics depends on the expression of the target vWF and are not dose proportional. Higher levels of vWF antigen increase the fraction of drug-target complex retained in the circulation. Steady-state was reached following the first administration of Caplacizumab-yhdp in healthy subjects, with minimal accumulation. Following a single subcutaneous dose of 10 mg caplacizumab-yhdp to healthy subjects the mean (CV%) peak concentration (Cmax) was 528 (20%) ng/ml and AUC0-24 was 7951 (16%). Following subcutaneous dosing of 10 mg caplacizumab-yhdp daily for 14 days to healthy subjects, the mean (CV%) Cmax was 348 (30%) ng/ml and AUC0-τ was 6808 (26%) hr·ng/ml.

Absorption

The bioavailability of subcutaneous caplacizumab-yhdp is approximately 90%.
The maximum concentration was observed 6 to 7 hours after subcutaneous dosing of 10 mg caplacizumab-yhdp once daily in healthy subjects.

Distribution

Caplacizumab-yhdp central volume of distribution is 6.33 L in patients with aTTP.

Elimination

The half-life of caplacizumab-yhdp is concentration and target-level dependent.

Metabolism

The available data suggest target-bound caplacizumab-yhdp is metabolized within the liver. Because caplacizumab-yhdp is a monoclonal antibody fragment, it is expected to be catabolized by various proteolytic enzymes.

Excretion

The available nonclinical data suggest unbound caplacizumab-yhdp is cleared renally.

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