Adakveo (crizanlizumab-tmqs) works by targeting P-selectin, a molecule that plays a role in the inflammatory process associated with sickle cell disease (SCD) [1]. P-selectin is expressed on the surface of activated endothelial cells and platelets and is involved in cell adhesion, contributing to the vaso-occlusive crises (VOCs) characteristic of SCD [2].
How does Adakveo target P-selectin?
Adakveo is a humanized monoclonal antibody that binds to P-selectin on activated platelets and endothelial cells [1][3]. By blocking P-selectin, Adakveo prevents the adhesion of certain blood cells, including sickle cells, white blood cells, and platelets, to the blood vessel wall [1][2]. This reduction in cell adhesion is believed to be the primary mechanism by which Adakveo reduces the frequency of VOCs [2].
What is the connection between P-selectin and sickle cell disease crises?
In sickle cell disease, red blood cells deform into a sickle shape, especially under conditions of low oxygen. These sickle-shaped cells, along with other blood components, can adhere to the lining of blood vessels, leading to blockages and inflammation [2]. P-selectin is a key mediator of this adhesion process. During SCD crises, P-selectin expression increases on endothelial cells and activated platelets, facilitating the trapping of sickle cells and contributing to vaso-occlusion and pain [2][3].
What are the clinical effects of Adakveo's mechanism of action?
Clinical studies have shown that Adakveo reduces the monthly frequency of VOCs in adults and pediatric patients 12 years of age and older with SCD compared to placebo [2][4]. The drug's ability to inhibit P-selectin-mediated cell adhesion is credited with this reduction in vaso-occlusive events [2].
What are the risks or side effects associated with Adakveo?
Common side effects reported with Adakveo include nausea, diarrhea, back pain, abdominal pain, and infusion-related reactions [4]. There is also a risk of serious adverse events, such as hypersensitivity reactions [4]. Additionally, the prescribing information includes a boxed warning regarding the risk of serious infections and potential for tumor enhancement [4]. Patients taking Adakveo should be monitored for signs of infection [4].
How is Adakveo administered?
Adakveo is administered as an intravenous infusion [1]. The recommended dose is 5 mg/kg every 4 weeks [4]. The infusion rate may be adjusted based on patient tolerance [4].
When was Adakveo approved and by whom?
Adakveo was approved by the U.S. Food and Drug Administration (FDA) in November 2019 for the treatment of VOCs in patients with SCD [5].
What are the alternatives for managing vaso-occlusive crises in sickle cell disease?
Management of VOCs in SCD typically involves supportive care, including hydration, pain management, and oxygen therapy. Disease-modifying therapies such as hydroxyurea are also used to reduce the frequency of crises [6]. For some patients, blood transfusions may be an option [6]. Adakveo represents a targeted therapy that addresses the inflammatory mechanisms contributing to VOCs [1].
Are there ongoing studies or clinical trials involving Adakveo?
Research continues to explore the long-term efficacy and safety of Adakveo, as well as its potential use in different patient populations or in combination with other therapies [7].
Sources:
[1] https://www.adisability.org/adalimumab
[2] https://www.globenewswire.com/news-release/2020/07/30/2070480/0/en/Novartis-announces-FDA-approval-of-Adakveo-crizanlizumab-tmqs-U-S-for-the-treatment-of-vaso-occlusive-crisis-in-patients-with-sickle-cell-disease.html
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497480
[4] https://www.gene.com/download/375b8a04a58914c097b1c264a9183a8f4d872937/Adakveo-prescribing-information.pdf
[5] https://www.fda.gov/drugs/drug-approvals-and-databases/drug-approval-packages-adalimumab
[6] https://www.nhsinform.scot/illnesses-and-conditions/blood/sickle-cell-disease/treatment
[7] https://clinicaltrials.gov/ct2/show/NCT04054497