Caplacizumab
Caplacizumab Uses, Dosage, Side Effects, Food Interaction and all others data.
Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019, and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.
In vitro studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.
In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.
| Trade Name | Caplacizumab |
| Availability | Prescription only |
| Generic | Caplacizumab |
| Caplacizumab Other Names | Caplacizumab, caplacizumab-yhdp |
| Related Drugs | Cablivi |
| Weight | 11mg |
| Type | Injectable kit |
| Formula | C1213H1891N357O380S10 |
| Weight | 27880.0 Da |
| Protein binding | This antibody acts directly on plasma proteins and thus, this parameter is not significant for drug description. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Caplacizumab is a von Willebrand factor (vWF)-directed antibody fragment used to treat acquired thrombotic thrombocytopenic purpura (aTTP).
Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.
aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.
Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.
Caplacizumab is also used to associated treatment for these conditions: Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
How Caplacizumab works
Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.
Toxicity
Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.
To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity
Food Interaction
No interactions found.Caplacizumab Disease Interaction
Volume of Distribution
The reported volume of distribution of caplacizumab is 6.33 L.
Elimination Route
After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours and it presents a very high bioavailability reaching approximately 90%.
The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.
Half Life
The reported half-life is reported to be in the range of 16-27 hours.
Clearance
As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description.
Elimination Route
The elimination of caplacizumab is divided between target-driven disposition which is driven by the binding to the von Willebrand factor and non-target disposition driven by the combination of catabolism and renal elimination.
Innovators Monograph
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