Crizanlizumab (SEG101, formerly SelG1) is an anti-P-selectin antibody being developed by Novartis as a potential treatment of sickle cell anemia.

How crizanlizumab works

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

P-selectin normally works to control the flow of white blood cells through blood vessels, and how they adhere to vessel walls, during periods of inflammation and tissue repair, perhaps caused by injury. In sickle cell anemia, it 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 pain crises.

Blocking, or inhibiting, P-selectin with crizanlizumab might prevent this adhesion molecule from starting the process that leads to blood vessel occlusion, inflammation and pain, and help to maintain normal blood flow.

Crizanlizumab in clinical trials

A Phase 2 clinical trial (NCT01895361), called SUSTAIN, evaluated the safety and effectiveness of crizanlizumab in 198 patients with sickle cell anemia and a history of two to 10 pain crises in the previous year. Patients received either a low dose of crizanlizumab (2.5 mg per kilogram of body weight), a high dose of crizanlizumab (5 mg per kilogram of body weight), or 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 sickle cell treatment, at a stable dose could continue that treatment.

Trial results were presented at the 2016 American Society of Hematology (ASH) 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 crizanlizumab significantly reduced the frequency of pain crises by 45.3 percent compared to placebo, while the low dose reduced these episodes by 32.6 percent, regardless of whether patients used hydroxyurea. The time until the first pain crisis was also 2.9 longer in the high-dose group than placebo-treated patients, and time to a second crisis was twice as long.

The most frequent adverse effects associated with crizanlizumab were joint pain, diarrhea, itching, vomiting, and chest pain.

According to investigators, these results suggested that crizanlizumab could treat patients with sickle cell anemia experiencing pain crises.

New findings from the SUSTAIN trial presented at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta further confirmed crizanlizumab’s at the high dose in patients.

A new Phase 2 trial (NCT03264989) is planned to further evaluate crizanlizumab at 5 mg/kg in about 45 adult patients with sickle cell anemia and vaso-occlusive pain events. The trial, which is not yet open to enrollment, aims to investigate the way crizanlizumab is absorbed, distributed and eliminated by the body (pharmacokinetics), as well as its effects on the body (pharmacodynamics). The safety and effectiveness of crizanlizumab will also be evaluated.

When the target number of enrolled patients is reached, the study aims to recruit 10 additional patients to evaluate crizanlizumab at a higher dose, 7.5 mg/kg.


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