Crizanlizumab

Last updated

Crizanlizumab
Monoclonal antibody
Type Whole antibody
Source Humanized
Target selectin P
Clinical data
Trade names Adakveo
Other namesSEG101, SelG1, crizanlizumab-tmca
AHFS/Drugs.com Monograph
MedlinePlus a620010
License data
Pregnancy
category
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6458H9948N1712O2050S58
Molar mass 146232.04 g·mol−1

Crizanlizumab, sold under the brand name Adakveo among others, is a monoclonal antibody medication that binds to P-selectin. [3] It is a medication used to reduce the frequency of vaso-occlusive crisis in people aged 16 years and older who have sickle cell anemia. [3] [4] [6] It is given by injection into a vein. [3] [4]

Contents

The most common side effects include joint pain, nausea, back pain, fever and abdominal (belly) pain. [4]

Crizanlizumab was approved for medical use in the United States in November 2019. [6] [7] [8] The EU's EMA withdrew authorization in May 2023 based on no significant effects from a phase 3 trial. [9] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [10]

Medical uses

Crizanlizumab is indicated for the prevention of recurrent vaso occlusive crises in sickle cell disease patients aged 16 years and older. [4] 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. [3] [4]

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 of hemoglobin). [11]

Pathophysiology

P-selectin molecules are present on the surface of activated platelets and vascular endothelial cells and have been linked to sickle cell vaso-occlusive crises. [12] [13] [14]

History

The US Food and Drug Administration (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. [8] The trial was conducted at 60 sites in the United States, Brazil and Jamaica. [8]

The FDA granted the application for crizanlizumab priority review, breakthrough therapy designation, and orphan drug designation. [6] The FDA granted approval of Adakveo to Novartis. [6] [8]

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. [15] 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. [16] [17]

Related Research Articles

<span class="mw-page-title-main">Hydroxycarbamide</span> Medical drug

Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and decreases the number of attacks. It is taken by mouth.

Richard D. Cummings is an American biochemist who is the S. Daniel Abraham Professor of Surgery at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts. He also the chief of the division of surgical sciences within the department of surgery. He is the director of the Harvard Medical School Center for Glycoscience, director of the National Center for Functional Glycomics, and also founder of the Glycomics Core at BIDMC. As of 2018 Cummings is also the scientific director of the Feihi Nutrition Laboratory at BIDMC. Before moving to BIDMC/HMS, Cummings was the William Patterson Timmie Professor and chair of the department of biochemistry at Emory University School of Medicine in Atlanta, Georgia from 2006 to 2015. At Emory, Cummings was a founder in 2007 of the Emory Glycomics Center.

The acute chest syndrome is a vaso-occlusive crisis of the pulmonary vasculature commonly seen in people with sickle cell anemia. This condition commonly manifests with a new opacification of the lung(s) on a chest x-ray.

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 sickle cell crisis when the circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries. The most common complaint is of pain, and recurrent episodes may cause irreversible organ damage. One of the most severe forms is the acute chest syndrome which occurs as a result of infarction of the lung parenchyma. This can rapidly result in death. Other types of vaso-occlusive crisis in sickle cell anemia include dactylitis, priapism, abdominal pain, and jaundice.

<span class="mw-page-title-main">Sickle cell disease</span> Group of genetic blood disorders

Sickle cell disease (SCD), one of the hemoglobinopathies, is a group of blood disorders typically inherited. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain, anemia, swelling in the hands and feet, bacterial infections, and stroke. Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.

<span class="mw-page-title-main">Ruxolitinib</span> Medication

Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.

Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

Betibeglogene autotemcel, sold under the brand name Zynteglo, is a gene therapy for the treatment for beta thalassemia. It was developed by Bluebird Bio and was given breakthrough therapy designation by the US Food and Drug Administration in February 2015.

<span class="mw-page-title-main">Difelikefalin</span> Chemical compound

Difelikefalin, sold under the brand name Korsuva, is an opioid peptide used for the treatment of moderate to severe itch. It acts as a peripherally-restricted, highly selective agonist of the κ-opioid receptor (KOR).

<span class="mw-page-title-main">Capmatinib</span> Chemical compound

Capmatinib, sold under the brand name Tabrecta, is an anticancer medication used for the treatment of metastatic non-small cell lung cancer whose tumors have a mutation that leads to the exon 14 skipping of the MET gene, which codes for the membrane receptor HGFR.

Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer.

Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). It is given by intravenous infusion. Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro.

Onasemnogene abeparvovec, sold under the brand name Zolgensma, is a gene therapy used to treat spinal muscular atrophy (SMA), a disease causing muscle function loss in children. It involves a one-time infusion of the medication into a vein. It works by providing a new copy of the SMN gene that produces the SMN protein.

<span class="mw-page-title-main">Voxelotor</span> Medication

Voxelotor, sold under the brand name Oxbryta, is a medication used for the treatment of sickle cell disease. Voxelotor is the first hemoglobin oxygen-affinity modulator. Voxelotor has been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators in sickle cell patients. It has a safe profile in sickle cell patients and healthy volunteers, without any dose-limiting toxicity. It was developed by Global Blood Therapeutics, a subsidiary of Pfizer.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

Ropeginterferon alfa-2b, sold under the brand name Besremi, is a medication used to treat polycythemia vera. It is an interferon. It is given by injection.

<span class="mw-page-title-main">Asciminib</span> Chemical compound

Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia. Asciminib is a protein kinase inhibitor.

Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy used for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. It was developed by Vertex Pharmaceuticals and CRISPR Therapeutics.


Lovotibeglogene autotemcel, sold under the brand name Lyfgenia, is a lentiviral gene therapy used for the treatment of sickle cell disease.

References

  1. 1 2 "AusPAR: Crizanlizumab". Therapeutic Goods Administration (TGA). 24 August 2021. Retrieved 4 September 2021.
  2. 1 2 "Adakveo". Therapeutic Goods Administration (TGA). 16 April 2021. Retrieved 6 September 2021.
  3. 1 2 3 4 5 "Adakveo- crizanlizumab injection". DailyMed. 8 September 2022. Retrieved 4 March 2023.
  4. 1 2 3 4 5 6 "Adakveo EPAR". European Medicines Agency. 20 July 2020. Retrieved 5 March 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ↑ "Adakveo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  6. 1 2 3 4 "FDA approves first targeted therapy to treat patients with painful complication of sickle cell disease". U.S. Food and Drug Administration (FDA) (Press release). 15 November 2019. Archived from the original on 21 November 2019. Retrieved 20 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ "Drug Approval Package: Adakveo (crizanlizumab-tmca)". U.S. Food and Drug Administration (FDA). 17 December 2019. Retrieved 22 January 2020.
  8. 1 2 3 4 "Drug Trials Snapshots Adakveo". U.S. Food and Drug Administration (FDA). 15 November 2019. Archived from the original on 24 January 2020. Retrieved 26 January 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ "Novartis sickle cell drug's approval formally revoked by EU regulators". BioPharma Dive. Retrieved 19 August 2023.
  10. ↑ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
  11. ↑ Darbari DS, Sheehan VA, Ballas SK (September 2020). "The vaso-occlusive pain crisis in sickle cell disease: Definition, pathophysiology, and management". European Journal of Haematology. 105 (3): 237–246. doi: 10.1111/ejh.13430 . PMID   32301178. S2CID   215801719.
  12. ↑ Manwani D, Frenette PS (December 2013). "Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies". Blood. 122 (24): 3892–3898. doi:10.1182/blood-2013-05-498311. PMC   3854110 . PMID   24052549.
  13. ↑ Manwani D, Frenette PS (December 2013). "Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies". Hematology. American Society of Hematology. Education Program. 2013: 362–369. doi:10.1182/asheducation-2013.1.362. PMC   3854110 . PMID   24319205.
  14. ↑ Riley TR, Boss A, McClain D, Riley TT (July 2018). "Review of Medication Therapy for the Prevention of Sickle Cell Crisis". P & T. 43 (7): 417–437. PMC   6027858 . PMID   30013299.
  15. ↑ EMA (26 May 2023). "EMA recommends revocation of authorisation for sickle cell disease medicine Adakveo". European Medicines Agency (Press release). Retrieved 26 May 2023.
  16. ↑ "Novartis provides update on Phase III STAND trial assessing crizanlizumab". Novartis (Press release). Retrieved 26 May 2023.
  17. ↑ "EMA recommends revocation of authorisation for sickle cell disease medicine Adakveo". European Medicines Agency (Press release). 26 May 2023. Retrieved 26 May 2023.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.