Clinical Trials

Date: 2017-12-11

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 59th American Society of Hematology (ASH) Annual Meeting in Orlando

Company: Novartis (Switzerland)

Product: crizanlizumab (SEG101)

Action mechanism:

• monoclonal antibody. Crizanlizumab (SEG101) is an investigational humanized anti-P-selectin monoclonal antibody that binds P-selectin on the surface of endothelial cells and platelets in the blood vessels, causing a blockade of P-selectin. This molecule is a driver of the vaso-occlusive process. Vaso-occlusive crises occur episodically when sickle-shaped red blood cells block blood flow through blood vessels. The therapeutic blockade of P-selectin can prevent painful vaso-occlusion in small blood vessels and maintain blood flow.
• The antibody has been developed by Selexys Therapeutics.

Disease: sickle cell disease

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• 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.
• A subgroup analysis has been performed and this post hoc analysis evaluated the time to first sickle cell pain crisis (SCPC) among subgroups of the SUSTAIN study population - those who had 2-4 or 5-10 SCPCs within the prior year; patients with HbSS or non-HbSS genotypes; and patients with or without concomitant treatment with hydroxyurea.
• The goal was to further assess the efficacy of crizanlizumab at 5.0 mg/kg per month vs placebo, and identify differences in treatment response among those subgroups.

Latest news:

• • On December 11, 2017 , Novartis announced that 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 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.
• Results, which were published in The New England Journal of Medicine last December, 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. 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 subpopulations 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 subpopulations, 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.
• 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. Crizanlizumab's filing is anticipated in the U.S. by the end of 2018.
• • On December 3, 2016, results from the Phase II SUSTAIN study show that SEG101 (crizanlizumab, formerly SelG1) reduced the median annual rate of sickle cell-related pain crises (SCPC) by 45.3% compared to placebo (1.63 vs 2.98, p=0.010) in patients with or without hydroxyurea therapy[1]. Novartis announced that the data have been presented at the 58th American Society of Hematology (ASH) Annual Meeting and presented during the Plenary Scientific Session tomorrow (Abstract #1, 2:00 - 4:00 p.m. PST). The results also are being published simultaneously in The New England Journal of Medicine. 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 SEG101 with or without hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises. Patients included in the study had a history of 2 to 10 pain crises in the previous 12 months. Patients receiving hydroxyurea or erythropoietin were included if prescribed for the preceding 6 months and dose was stable for at least 3 months. The trial randomized 198 patients age 16 to 65 to receive high dose SEG101, low dose SEG101 or placebo. In the study, patients were assigned to high-dose (5.0 mg/kg), low-dose (2.5 mg/kg) and placebo arms. The study met its primary endpoint, reduction of the annual rate of SCPC in the high-dose arm by 45.3% vs. placebo (medians of 1.63 vs. 2.98, p=0.010). In the low- dose arm, the annual rate of SCPC was reduced by 32.6% vs. placebo (medians of 2.01 vs. 3.0, p = 0.180). For patients in the high dose arm, time to first SCPC vs. placebo was 2.9 times longer (medians of 4.07 vs. 1.38 months, p = 0.001) and time to second SCPC was 2.0 times longer than placebo (medians of 10.32 vs. 5.09 months, p = 0.022). Despite its availability, hydroxyurea often is not utilized primarily due to concerns about patient compliance and potential adverse events.

Is general: Yes