Cablivi is the first therapeutic approved in Europe, for the treatment of a rare blood-clotting disorder
On September 03, 2018, the European Commission has granted marketing authorization for Cablivi™ (caplacizumab) for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), a rare blood-clotting disorder. Cablivi is the first therapeutic specifically indicated for the treatment of aTTP 1. Cablivi was designated an ‘orphan medicine’ (a medicine used in rare diseases) on April 30, 2009. The approval of Cablivi in the EU is based on the Phase II TITAN and Phase III HERCULES studies in 220 adult patients with aTTP. The efficacy and safety of caplacizumab in addition to standard-of-care treatment, daily PEX and immunosuppression, were demonstrated in these studies. In the HERCULES study, treatment with caplacizumab in addition to standard-of-care resulted in a significantly shorter time to platelet count response (p<0.01), the study’s primary endpoint; a significant reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event during study drug treatment (p<0.0001); and a significantly lower number of aTTP recurrences in the overall study period (p<0.001). Importantly, treatment with caplacizumab resulted in a clinically meaningful reduction in the use of PEX and length of stay in the intensive care unit (ICU) and the hospital, compared to the placebo group. Cablivi was developed by Ablynx, a Sanofi company. Sanofi Genzyme, the specialty care global business unit of Sanofi, will work with relevant local authorities to make Cablivi available to patients in need in countries across Europe.
About aTTP aTTP is a life-threatening, autoimmune blood clotting disorder characterized by extensive clot formation in small blood vessels throughout the body, leading to severe thrombocytopenia (very low platelet count), microangiopathic hemolytic anemia (loss of red blood cells through destruction), ischemia (restricted blood supply to parts of the body) and widespread organ damage especially in the brain and heart. About Cablivi Caplacizumab blocks the interaction of ultra-large von Willebrand Factor (vWF) multimers with platelets and, therefore, has an immediate effect on platelet adhesion and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia and organ dysfunction in aTTP 2.
Note – Caplacizumab is a bivalent anti-vWF Nanobody that received Orphan Drug Designation in Europe and the United States in 2009, in Switzerland in 2017 and in Japan in 2018. The U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application for caplacizumab for treatment of adults experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019
1 http://hugin.info/152918/R/2213684/863478.pdf
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EVQLVESGGG LVQPGGSLRL SCAASGRTFS YNPMGWFRQA PGKGRELVAA ISRTGGSTYY
PDSVEGRFTI SRDNAKRMVY LQMNSLRAED TAVYYCAAAG VRAEDGRVRT LPSEYTFWGQ
GTQVTVSSAA AEVQLVESGG GLVQPGGSLR LSCAASGRTF SYNPMGWFRQ APGKGRELVA
AISRTGGSTY YPDSVEGRFT ISRDNAKRMV YLQMNSLRAE DTAVYYCAAA GVRAEDGRVR
TLPSEYTFWG QGTQVTVSS
(disulfide bridge: 22-96, 153-227)
Sequence:
EU 2018/8/31 APPROVED, Cablivi
Treatment of thrombotic thrombocytopenic purpura, thrombosis
Other Names
- 1: PN: WO2011067160 SEQID: 1 claimed protein
- 98: PN: WO2006122825 SEQID: 98 claimed protein
- ALX 0081
- ALX 0681
- Caplacizumab
| Formula |
C1213H1891N357O380S10
|
|---|---|
| CAS |
915810-67-2
|
| Mol weight |
27875.8075
|
Caplacizumab (ALX-0081) (INN) is a bivalent VHH designed for the treatment of thrombotic thrombocytopenic purpura and thrombosis.[1][2]
This drug was developed by Ablynx NV.[3] On 31 August 2018 it was approved in the European Union for the “treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression”.[4]
It is an anti-von Willebrand factor humanized immunoglobulin.[5] It acts by blocking platelet aggregation to reduce organ injury due to ischemia.[5] Results of the phase II TITAN trial have been reported.[5]
PATENTS
WO 2006122825
WO 2009115614
WO 2011067160
WO 2011098518
WO 2011162831
WO 2013013228
WO 2014109927
WO 2016012285
WO 2016138034
WO 2016176089
WO 2017180587
WO 2017186928
WO 2018067987
References
- Jump up^ Statement On A Nonproprietary Name Adopted By The USAN Council – Caplacizumab, American Medical Association.
- Jump up^ World Health Organization (2011). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 106”(PDF). WHO Drug Information. 25 (4).
- Jump up^ A Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura (HERCULES)
- Jump up^ European Medicines Agency. “An overview of Cablivi and why it is authorised in the EU” (PDF). Retrieved 1 October 2018.
- ^ Jump up to:a b c Immune Drug Tackles Microvascular Thrombosis Disorder. Feb 2016
| Monoclonal antibody | |
|---|---|
| Type | Single domain antibody |
| Source | Humanized |
| Target | VWF |
| Clinical data | |
| Synonyms | ALX-0081 |
| ATC code |
|
| Identifiers | |
| CAS Number | |
| ChemSpider |
|
| KEGG | |
| Chemical and physical data | |
| Formula | C1213H1891N357O380S10 |
| Molar mass | 27.88 kg/mol |
/////////////eu 2018, Caplacizumab, nti-vWF Nanobody, Orphan Drug Designation, aTTP, Cablivi, Ablynx, Sanofi , ALX-0081, カプラシズマブ , PEPTIDE, ALX 0081