The frequency of sickle cell-related pain crises (SCPC) is reduced significantly by high-dose SelG1 among patients with sickle cell disease, with or without hydroxyurea treatment, according to a study presented here at the 2016 Annual Meeting of the American Society of Hematology (ASH).
SelG1 is a P-selectin inhibitor, said Kenneth I. Ataga, MD, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, on December 3.
“Acute painful crises are the primary cause of healthcare encounters in patients with sickle cell disease,” said Dr. Ataga, lead investigator of the SUSTAIN trial.
Pain is caused by tissue ischaemia created when sickled red blood cells and leukocytes adhere to the endothelium, leading to vasoocclusion. SCPCs occur unpredictably and often require hospitalisation.
Dr. Ataga explained that, although hydroxyurea is known to decrease SCPC frequency in sickle cell anaemia, many patients receiving hydroxyurea continue to experience acute painful episodes.
Upregulation of P-selectin, an adhesion molecule expressed on activated vascular endothelial cells and platelets, plays a key role in the pathogenesis of SCPC. SelG1 is a first-in-class humanised anti-P-selectin antibody that is given as an intravenous infusion over 30 minutes.
In the multinational SUSTAIN study, patients were randomised to placebo (n = 65) or SelG1 2.5 mg/kg (n = 66) or 5.0 mg/kg (n = 67). Patients received an initial dose, another dose on day 14, and then a dose every 4 weeks through week 50, for a total of 14 doses. The primary efficacy endpoint of the study was the annual rate of SCPC in the 5.0-mg/kg SelG1 group versus the placebo group. 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.
The median age of the patients (~45% male, ~93% black or African American) was 28 years. Sixty-two percent of the patients were taking hydroxyurea concomitantly.
The median rate of SCPC per year was 1.63 for patients receiving the high-dose SelG1, 2.01 for those receiving low-dose SelG1, and 2.98 for those receiving placebo. In the high-dose group, 24 patients were SCPC free. Twelve patients in the low-dose SelG1 group were SCPC free over the course of the study, as were 11 in the placebo group. Median time to first and second SCPC events was significantly longer in the high-dose SelG1 group (4.07 and 10.32 mo, respectively) than in the placebo group (1.38 and 5.09 mo, respectively) (P = .001 and .022, respectively). Differences between the low-dose SelG1 and placebo groups were not significant.
The incidence of adverse events with SelG1 treatment was low, said Dr. Ataga, who concluded, “Treatment with high-dose SelG1 resulted in a statistically significant and clinically meaningful reduction in the frequency of SCPC in patients with sickle cell disease.”