Crizanlizumab, sold under the brand name Adakveo among others, is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

medication that binds to

P-selectin P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene. P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and a ...

. It is a medication used to reduce the frequency of

vaso-occlusive crisis A vaso-occlusive crisis is a common painful complication of sickle cell anemia in adolescents and adults. It is a form of sickle cell crisis. Sickle cell anemia – most common in those of African, Hispanic, and Mediterranean origin – leads to ...

in people aged 16 years and older who have

sickle cell anemia Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...

. It is given by injection into a vein. The most common side effects include joint pain, nausea, back pain, fever and abdominal (belly) pain. Crizanlizumab was approved for medical use in the United States in November 2019. The EU's EMA withdrew authorization in May 2023 based on no significant effects from a phase 3 trial. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

Crizanlizumab is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the prevention of recurrent vaso occlusive crises in sickle cell disease patients aged 16 years and older. It can be given as an add on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. Vaso-occlusive crisis is a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells (red cells are usually round and flexible, but sometimes many red cells in a person with sickle cell anemia will become rigid and crescent-shaped due to

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

of hemoglobin).

Pathophysiology

molecules are present on the surface of activated platelets and vascular

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

s and have been linked to sickle cell vaso-occlusive crises.

History

The US

(FDA) approved crizanlizumab based on evidence from one clinical trial (Trial 1/NCT01895361) of 132 participants with sickle cell diseases who had a history of vaso-occlusive crisis. The trial was conducted at 60 sites in the United States, Brazil and Jamaica. The FDA granted the application for crizanlizumab priority review, breakthrough therapy designation, and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation. The FDA granted approval of Adakveo to

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

. The European Medicines Agency's human medicines committee (CHMP) has recommended the withdrawal of Adakveo (crizanlizumab), a medicine for preventing vaso-occlusive crises in patients with sickle cell disease, due to the lack of sufficient benefits outweighing the risks. The STAND phase III study showed that Adakveo does not effectively reduce the number of painful crises requiring healthcare visits or treatment at home compared to a placebo, and it exhibits a higher rate of severe side effects.

References

External links

* Hematology Monoclonal antibodies Orphan drugs Sickle-cell disease {{blood-drug-stub