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The anti-P-selectin antibody SelG1 reduces and delays the incidence of sickle-cell related pain crises

Acute painful episodes, frequently called sickle cell-related pain crises (SCPC), are a substantial cause of morbidity in sickle cell disease (SCD). Results of a randomized, double-blind, placebo-controlled phase II study demonstrated that SelG1, a first-in-class humanized anti-P-selectin antibody, reduced the rate of SCPC by 45% in SCD patients. In addition to this, the median times to the 1st and 2nd SCPC with high-dose SelG1 were 2 to 3 times as long as in patients who received placebo. Interestingly, the incidence of adverse events with SelG1 was low.

While normal red blood cells are flexible and can easily move through blood vessels, sickled cells are prone to sticking together and to other blood cells and to the lining of blood vessels, which obstructs blood flow, interrupts oxygen delivery to the body’s tissues, and causes severe pain. These painful episodes occur unpredictably and often require hospitalization. Although hydroxyurea (HU) is known to decrease the frequency of SCPC in sickle cell anemia, many patients continue to experience acute painful episodes despite HU. P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on the vessel wall that leads to firm attachment and extravasation to underlying tissues during inflammation. Upregulation of P-selectin on endothelial cells and platelets also contributes to the cell-cell interactions involved in the pathogenesis of SCPC. The phase II SUSTAIN study evaluated the safety of SelG1, as well as its effect on the frequency of SCPC in SCD patients.

In the presented study, 198 patients were randomized to receive placebo, 2.5 mg/kg or 5.0 mg/kg SelG1. Patients received their initial dose, followed by a second dose 14 days later, and then every 4 weeks through week 50 for a total of 14 doses. The primary endpoint of the study was the annual rate of SCPC. An SCPC was defined as acute sickle cell-related pain that resulted in a visit to a medical facility and required a parenteral or oral narcotic or parenteral NSAID. Acute chest syndrome (ACS), priapism, hepatic and splenic sequestration were also included in this definition. Secondary objectives of the SUSTAIN study included the annual rate of hospitalization days, times to first and second SCPC and the annual rate of uncomplicated SCPC (defined as typical SCPC other than ACS, priapism and hepatic or splenic sequestration) and ACS. Patients aged 16 to 65 years with a diagnosis of SCD (HbSS, HbSC, HbSβ0 thalassemia or HbSβ+ thalassemia) and a history of 2 to 10 SCPC episodes in the previous 12 months, were eligible for the study. Patients receiving HU or erythropoietin were included if prescribed for the preceding 6 months with a stable dose for at least 3 months.

The annual rate of SCPC in patients receiving the high-dose SelG1 was 1.63 as compared to 2.98 with placebo. This corresponds to a 45.3% lower annual SCPC rate with high-dose SelG1 as compared to placebo (p= 0.01). The SelG1 drug effect was dose-dependent as the annual rate of SCPC at 2.5 mg/kg vs. placebo was reduced by 32.6% (p= 0.180). Looking at the secondary endpoints, the time to the first SCPC was 2.9 times longer with high-dose SelG1 than what was seen with placebo (median 4.07 months vs. 1.38 months; p=0.01). With the 2.5mg/kg dose of SelG1, the median time to the first SCPC was 2.2 months. The time to the 2nd SCPC was 2 times longer with high-dose SelG1 than with placebo (median 10.32 vs. 5.09 months; p= 0.022). The annual rate of uncomplicated SCPC at the 5.0mg/kg dose vs. placebo was reduced by 62% (medians of 1.1 vs. 2.9, p = 0.015). ACS events were rare in this study. The annual rate of days hospitalized at 5.0 mg/kg vs. placebo showed a non-significant, 42% reduction (medians of 4.0 vs. 6.9, p = 0.450).

In conclusion, the treatment with high dose SelG1 resulted in a statistically significant and clinically meaningful reduction in the frequency of SCPC in patients with SCD. Of note, this substantial reduction in the frequency of SCPC with high-dose SelG1 as compared to placebo was seen regardless of concomitant HU usage or SCD genotype. In addition to this, the median times to 1st and 2nd SCPC crisis with high-dose SelG1 were 2- to 3-fold longer than what was seen in patients who received placebo. The incidence of adverse events with SelG1 treatment was low.


Ataga K, Kutlar A, Julie Kanter J et al. SUSTAIN: A Multicenter, Randomized, Placebo-Controlled, Double-Blind, 12-Month Study to Assess Safety and Efficacy of SelG1 with or without Hydroxyurea Therapy in Sickle Cell Disease Patients with Sickle Cell-Related Pain Crises. Presented at ASH 2016; Abstract 1.

Speaker Kenneth Ataga


Kenneth I. Ataga, MD, Professor of Medicine,
Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA


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