- Investigational therapy
crizanlizumab (SEG101, formerly SelG1)
approximately doubled the time to first
on-treatment sickle cell pain crisis, according to new subgroup
analysis of Phase II SUSTAIN data
- Results were consistent across
patient subgroups despite differences in disease severity, genotype
or background therapy
- New findings for crizanlizumab,
a potential disease-modifying, preventive treatment option for
patients with sickle cell disease, presented at ASH 2017
- Discussions with health
authorities continue; FDA filing anticipated by end of 2018
pending outcome of ongoing healthy volunteer bridging
study
Basel, December 11, 2017 -
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[1]. 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.[2]
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 subpopulations and with
hydroxyurea use[1].
"Pain is the primary cause of suffering in sickle
cell disease," said Julie Kanter, M.D., Division of Pediatrics,
Medical University of South Carolina, a study investigator. "What
this new analysis of the SUSTAIN data suggests is that once
patients start crizanlizumab, they are likely to have a longer time
before experiencing another pain crisis. These findings are
consistent regardless of the severity of disease, genotype, or the
use of background therapy. That is a potentially promising new
development for patients. Fewer pain crises mean less organ damage
long term."
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[1].
"This analysis from SUSTAIN is another important
step to bringing what we hope will be a new disease-modifying
therapy to patients with sickle cell disease," said Samit Hirawat,
MD, Head, Novartis Oncology Global Drug Development. "The results
are consistent among different groups of patients, which gives us
even more confidence in our development program for this promising
medicine."
About the Subgroup Analysis and
the SUSTAIN trial
The heterogeneity in severity of sickle cell disease and various
other factors make it important to understand differences in
response of various subgroups of patients in order to increase
understanding of crizanlizumab and the role of P-selectin in SCD.
This post hoc analysis evaluated the time to first 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[1].
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.[3] 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.[3]
About crizanlizumab (SEG101)
Crizanlizumab (SEG101) is an investigational humanized
anti-P-selectin monoclonal antibody that binds a molecule called
P-selectin on the surface of endothelial cells and platelets in the
blood vessels, causing a blockade of P-selectin[3],[4]. P-selectin
is a driver of the vaso-occlusive process[3],[5].
Vaso-occlusive crises, also known as SCPCs, occur
episodically when sickle-shaped red blood cells block blood flow
through blood vessels[6]. The therapeutic blockade of P-selectin
can prevent painful vaso-occlusion in small blood vessels and
maintain blood flow[3],[6].
Disclaimer
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by words such as "potential," "can," "will," "plan," "expect,"
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express or implied discussions regarding potential marketing
approvals, new indications or labeling for the investigational or
approved products described in this press release, or regarding
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actual results may vary materially from those set forth in the
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particular time. Nor can there be any guarantee that such products
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and factors referred to in Novartis AG's current Form 20-F on file
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About Novartis
Novartis provides innovative healthcare solutions that address the
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these needs: innovative medicines, cost-saving generic and
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References
[1] Kanter J,
Kutlar A, Liles D, et al. Crizanlizumab 5.0 mg/kg increased the
time to first on-treatment sickle cell pain crisis: A subgroup
analysis of the Phase II SUSTAIN study. Abstract #613. 2017 59th
American Society of Hematology (ASH) Annual Meeting, Atlanta,
GA.
[2] Puri L, Nottage
K et al. State of the Art Management of Acute Vaso-occlusive
Pain in Sickle Cell Disease Pediatr Drugs, epub Aug 2017 DOI
10.1007/s40272-017-0263-z
[3] Ataga KI,
Kutlar A, Kanter J et al. Crizanlizumab for the Prevention of
Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb
2;376(5):429-439.
[4] Miller ST, Kim
HY, et al. for Sickle Cell Disease Clinical Research Network
(SCDCRN). Inpatient management of sickle cell pain: A 'snapshot' of
current practice. Am J Hematol. 2012 Mar;87(3):333-336.
[5] Novartis
Pharmaceuticals Corporation. Data on file. 2016.
[6] Quinn CT.
Anti-adhesive therapy for sickle cell disease. The Hematologist.
2014; 11(6):15.
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