EAST HANOVER, N.J.,
Dec. 11, 2017 /PRNewswire/
-- 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 disease1.
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 use1.
"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 therapy1.
"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 subgroups1.
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-selectin3,4. P-selectin is a driver of the
vaso-occlusive process3,5. Vaso-occlusive crises,
also known as SCPCs, occur episodically when sickle-shaped red
blood cells block blood flow through blood vessels6. The
therapeutic blockade of P-selectin can prevent painful
vaso-occlusion in small blood vessels and maintain blood
flow3,6.
Disclaimer
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regarding potential marketing approvals, new indications or
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subject to significant known and unknown risks and uncertainties.
Should one or more of these risks or uncertainties materialize, or
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Novartis AG's current Form 20-F on file with the US Securities and
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About Novartis
Located in East Hanover, NJ Novartis Pharmaceuticals
Corporation is an affiliate of Novartis which provides innovative
healthcare solutions that address the evolving needs of patients
and societies. Headquartered in Basel,
Switzerland, Novartis offers a diversified portfolio to best
meet these needs: innovative medicines, cost-saving generic and
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References
- 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.
- 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
- 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.
- 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.
- Novartis Pharmaceuticals Corporation. Data on file. 2016.
- Quinn CT. Anti-adhesive therapy for sickle cell disease. The
Hematologist. 2014; 11(6):15.
Novartis Media Relations
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E-mail: media.relations@novartis.com
Eric
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SOURCE Novartis Pharmaceuticals Corporation