Adakveo (crizanlizumab) is an anti-P-selectin antibody that was developed by Novartis and has been approved by the U.S. Food and Drug Administration (FDA) as a treatment for painful vaso-occlusive crisis events caused by sickle cell disease in patients 16 and older.

What is sickle cell disease?

Sickle cell disease is a rare genetic disorder that affects red blood cells. Normal red blood cells have a flexible disk-like shape that allows them to move easily through the smallest blood vessels. In sickle cell disease, the red blood cells assume a sickle-shaped appearance, and clump or aggregate. The aggregates are unable to flow through small blood vessels, preventing oxygen from reaching tissues. These aggregates cause inflammation and episodes of pain called vaso-occlusive pain crises.

How does Adakveo work?

Adakveo contains a monoclonal antibody, a molecule made in the laboratory to bind P-selectin, a protein that is found on the surface of endothelial cells (the cells that line the inner walls of blood vessels) and in platelets (blood cells that are involved in clotting).

P-selectin normally works to control the flow of white blood cells through blood vessels and how they adhere to blood vessel walls during periods of inflammation and tissue repair, such as after an injury. In sickle cell disease, P-selectin contributes to the adhesion of sickle red blood cells (cells with an abnormal crescent shape) to blood vessels, preventing blood flow through smaller vessels. This causes inflammation and vaso-occlusive pain crises.

By blocking or inhibiting P-selectin, Adakveo prevents this adhesion molecule from starting the process that leads to blood vessel occlusion, inflammation, and pain, and helps to maintain normal blood flow.

After two initial doses given two weeks apart in the first month, the treatment must be administered once a week at 5 mg per kg of body weight by infusion into the bloodstream once per month.

Adakveo in clinical trials

A Phase 2 clinical trial (NCT01895361), called SUSTAIN, evaluated the safety and effectiveness of Adakveo in 198 patients with sickle cell disease and a history of two to 10 vaso-occlusive pain crises in the previous year. Patients received either a low dose of Adakveo (2.5 mg per kg of body weight), a high dose (5 mg per kg of body weight), or a placebo, given as an injection into the bloodstream 14 times over a period of 52 weeks (generally, every four weeks). Patients using hydroxyurea, a common treatment for sickle cell disease, at a stable dose could continue that treatment.

Trial results were presented at the 2016 American Society of Hematology annual meeting, in San Diego, California, and published in The New England Journal of Medicine in early 2017.

They showed that the high dose of Adakveo significantly reduced the frequency of vaso-occlusive pain crises by 45.3% compared with the placebo, while the low dose reduced these episodes by 32.6%, regardless of whether or not patients used hydroxyurea. The time until the first pain crisis was also 2.9 times longer in the high-dose group than in placebo-treated patients, and time to a second crisis was twice as long.

The most frequent adverse effects associated with the use of Adakveo were joint pain, diarrhea, itching, vomiting, and chest pain.

New findings from the SUSTAIN trial presented at the 2017 ASH annual meeting in Atlanta further confirmed Adakveo’s efficacy at the high dose in patients with sickle cell disease.

A new Phase 2 trial (NCT03264989) is currently recruiting in the U.S. to further evaluate Adakveo at a dose of 5 mg/kg in sickle cell disease patients, 16 to 70 years old, with vaso-occlusive pain crises. The trial aims to investigate the way Adakveo is absorbed, distributed, and eliminated by the body (pharmacokinetics), as well as its effects on the body (pharmacodynamics). The safety and effectiveness of the treatment will also be evaluated.

Once the target number of 45 patients have been enrolled, the study plans to recruit 10 more patients to evaluate Adakveo at a higher dose of 7.5 mg/kg.

An open-label Phase 2 clinical trial (NCT03474965) is recruiting up to 100 patients, 6 months to 17 years old, with sickle cell disease who have had at least one vaso-occlusive crisis in the past year. The study is designed to establish the appropriate dose of Adakveo for this patient population, and is recruiting at sites around the world


Last updated: Nov. 25, 2019


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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.