New treatment for acute sickle cell pain crises

Results from a post hoc subgroup analysis of the Phase II SUSTAIN study show that crizanlizumab, an investigational humanized anti-P-selectin monoclonal antibody, delayed the time to first sickle cell pain crisis (SCPC) in patients vs. placebo in key subgroups of adult patients with sickle cell disease.

Findings were featured during an oral session at the 59th American Society of Hematology (ASH) Annual Meeting (Abstract #613; Monday, December 11, 10:30 AM ET). Acute sickle cell pain crises, also referred to as vaso-occlusive crises, are a common painful complication of the disease and the main reason that patients seek medical care in hospitals. Currently, treatment options are limited.

The data from a subgroup analysis of the Phase II SUSTAIN study showed that crizanlizumab, at 5.0 mg/kg per month increased the time to SCPC in patients on treatment, including those in high-risk sub-populations and with hydroxyurea use. The analysis looked at the following subgroups of patients with sickle cell disease:

• Patients with 2-4 or 5-10 SCPC events in the year before the study.

• Patients with the HbSS genotype, and non-HbSS genotypes

• Patients who were or were not taking hydroxyurea . In all of these sub-populations, crizanlizumab at 5.0 mg/kg per month increased the estimated median time to first SCPC vs. placebo by approximately two-fold or more. In patients taking crizanlizumab who experienced 2-4 SCPCs in the prior year, time to first on-treatment pain crisis was 4.8 vs 1.6 months with placebo (HR 0.53 with 95% CI [0.31, 0.90]). For patients with 5-10 SCPCs in the prior year, time to first on-treatment pain crisis was 2.4 vs 1.0 months (HR 0.47 with a 95% CI [0.25, 0.89]). In patients with the HbSS genotype, there was a 3.7-fold increase in estimated median time to first SCPC in those taking crizanlizumab vs. placebo (4.1 vs 1.1 months; HR 0.50 with 95% CI [0.31, 0.80]). In patients taking hydroxyurea, the time to first on-study SCPC was longer with crizanlizumab vs placebo (2.4 vs 1.2 months; HR 0.58 with 95% CI [0.35, 0.96]), suggesting its potential as an additive therapy.

The SUSTAIN trial was a multicenter, multinational, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of the anti-P-selectin antibody crizanlizumab with or without concomitant use of hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises. Results, which were published in The New England Journal of Medicine, showed that crizanlizumab reduced the median annual rate of SCPCs by 45% compared to placebo (1.6 vs 3.0, p=0.01) in patients with or without hydroxyurea therapy. These data will help support discussions with regulatory agencies, with filing anticipated in the U.S. by the end of 2018. Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. There were no apparent increases in infections with crizanlizumab treatment.

Comment: Novartis acquired Selexys Pharmaceuticals Corporation after receipt of positive results from SUSTAIN trial.