ARCALYST SUMMARY
Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells.
ARCALYST is supplied in single-use, 20-mL glass vials containing a sterile, white to off-white, lyophilized powder. Each vial of ARCALYST is to be reconstituted with 2.3 mL of Sterile Water for Injection. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and essentially free from particulates. Each vial contains 220 mg rilonacept. After reconstitution, each vial contains 80 mg/mL rilonacept, 40 mM histidine, 50 mM arginine, 3.0% (w/v) polyethylene glycol 3350, 2.0% (w/v) sucrose, and 1.0% (w/v) glycine at a pH of 6.5 ± 0.3. No preservatives are present.
ARCALYST® (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older.
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NEWS HIGHLIGHTSMedia Articles Related to Arcalyst (Rilonacept)
Regeneron Announces FDA Acceptance Of ARCALYST® (rilonacept) Supplemental Biologics License Application For Review
Source: Gout News From Medical News Today [2011.11.26]
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Company's supplemental Biologics License Application (sBLA) for ARCALYST Injection for Subcutaneous Use for the prevention of gout flares in patients initiating uric acid-lowering therapy...
Clinical Trial Demonstrates That Rilonacept Significantly Reduces Gout Flares
Source: Gout News From Medical News Today [2012.01.09]
A phase II clinical trial found that rilonacept, an inhibitor of the protein interleukin-1 (IL-1), significantly reduced acute gout flares that occur when initiating uric acid-lowering therapy...
Gout Flares - Rilonacept Effective, According To Clinical Trial
Source: Gout News From Medical News Today [2012.01.06]
According to a phase II clinical trial, the drug rilonacept, which inhibits the protein interleukin-1 (IL-1), substantially reduces acute gout flares that occur at the start of uric acid-reducing therapy and is noted to be generally well tolerated with no serious infections or serious adverse events occurring in relation to the treatment...
Published Studies Related to Arcalyst (Rilonacept)
Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during
initiation of urate-lowering therapy: results of a phase II randomized,
double-blind, placebo-controlled trial. [2012]
initiation of urate-lowering therapy... CONCLUSION: The current findings indicate that rilonacept significantly reduces
Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with
cryopyrin-associated periodic syndromes: results from two sequential
placebo-controlled studies. [2008]
autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS)... CONCLUSION: Treatment with weekly rilonacept provided marked and lasting
Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever:
a randomized trial. [2012]
FMF... CONCLUSION: Rilonacept reduces the frequency of FMF attacks and seems to be a
Clinical Trials Related to Arcalyst (Rilonacept)
Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD) [Recruiting]
Risk of cardiovascular diseases (CVD) is significantly elevated in patients with chronic
kidney disease (CKD); however, this increased risk is only partially explained by
traditional cardiovascular risk factors. Patients with CKD exhibit chronic inflammation, a
key mechanism contributing to vascular dysfunction (i. e., large elastic artery stiffening
and endothelial dysfunction). Inhibiting inflammation improves vascular dysfunction in
other populations characterized by chronic inflammation. However, it is currently unknown
if reducing inflammation with an interleukin-1 (IL-1) blocker enhances vascular function in
CKD patients. Aim 1 will assess the efficacy of IL-1 blocking with rilonacept for treating
vascular dysfunction in patients with stage III or IV CKD (estimated glomerular filtration
rate 20-60 mL/min/1. 73 m2). Aim 2 will determine if blocking IL-1 with rilonacept also
reduces inflammation and oxidative stress. These studies could shift clinical practice
guidelines by establishing a novel therapy for reducing CVD risk in CKD patients not
requiring chronic hemodialysis.      
IL1-TRAP, Rilonacept, in Systemic Sclerosis [Recruiting]
Scleroderma,also known as systemic sclerosis (SSc), is a multisystem disease affecting skin
and other tissues including joints, muscles, lungs, the gastrointestinal tract and kidneys
and tissue fibrosis is widespread. SSc presents special problems for developing therapies
due to the heterogeneous clinical presentation, the variability of disease progression and
the difficulty quantifying the extent of disease. For most disease manifestations, treatment
is primarily symptomatic and generally inadequate.
This study will utilize a 4-gene biomarker of skin disease as the primary efficacy outcome
in a short duration, placebo-controlled clinical trial of rilonacept, designed to provide
preliminary data for a larger trial. These gene biomarkers should provide a strong surrogate
for such trials in the future and, if IL-1 is indeed the cytokine leading to fibrosis in
this disease, provide a highly significant start to finding a therapeutic for SSc that for
the first time might dramatically affect fibrosis. A central hypothesis of this study is
that IL-1 inhibition will downregulate the 4-gene biomarker over a relatively short period
of time, much shorter than is historically thought necessary to see changes in the MRSS, a
skin score measurement tool. Entry criteria will include the recent onset of diffuse
cutaneous SSc as this is the population most likely to show progressive skin disease and
also the population examined in previous studies showing correlations between MRSS and the
4-gene biomarker.
Secondary outcomes will include other validated measures of SSc disease activity. MRSS and
SSc health assessment questionnaire (SHAQ), will be followed during the trial. This study
will also test the effect of rilonacept on global skin gene expression using microarray
analyses of skin biopsies. In addition, serum biomarkers of SSc disease activity (COMP,
THS-1 and IFI44) and a biomarker of inflammasome activation (CRP) will be tested before and
after treatment.
Inflammation in Chronic Kidney Disease and Cardiovascular Disease - The Role of Genetics and Interleukin-1 Receptor Antagonist (IL-1ra) [Not yet recruiting]
There has been an exponential growth in the number of people with Chronic Kidney Disease
(CKD) needing dialysis or transplantation, increasing from 209,000 in 1991 to 472,000 in
2004. This is highly concerning due to both the human cost and the burden that it
represents to the health care system. Recent comparison of the NHANES surveys showed that
CKD prevalence increased from 10% in 1988-1994 to 13% in 1999-2004. Patients with CKD are
more likely to die from premature CV death than to reach ESRD. In those that reach ESRD,
cardiovascular disease (CVD) accounts for over half of the deaths in dialysis. The
prevalence of CKD for the VA population is 20%, and 31. 6% for diabetics, higher than in the
general population. These observations emphasize the need of risk stratification, early
detection, and prevention efforts with respect to CKD progression and the CVD burden that
afflicts CKD through targeted interventions in high-risk groups (personalized medicine).
CKD is multifactorial, however familial aggregation of end-stage renal disease(ESRD) and CKD
have been reported for all types of nephropathy underscoring "kidney disease genetic
susceptibility ". Genetic predisposition to ESRD is stronger in African Africans. African
Americans with a first-degree relative with ESRD have a 9-fold increase risk of ESRD VS a
3-5 fold increase in whites.
Studies consistently show that CKD is an inflammatory process and that biomarkers of
inflammation increase since early stages of CKD. CVD is also an inflammatory process, and
genes that affect inflammation are associated with higher risk of CVD. Since inflammation
is a common denominator of both disease processes (CKD and CVD), it is likely that genes
that govern inflammation may be involved in both, the predisposition to CKD and the burden
of CVD attributable to CKD. Additionally if inflammation plays a central role in the burden
of CVD in CKD than drugs that modulate inflammation should impact both: CKD progression and
non-traditional CV risk factors and CVD.
The overall goal of this proposal is to study genetic predisposition to CKD, and CVD risk in
CKD through inflammatory pathways, and the effect that a potent anti-inflammatory
intervention like interleukin 1 receptor antagonist (IL-1ra), will have in inflame patients
with CKD stages 3&4. Specific Aims: 1)To determine if specific polymorphism/haplotypes,
genotype combinations and gene-environmental interactions that can affect inflammation,
available from the Third National Health and Nutrition Examination Survey (DNA data set),
specifically in the CRP,IL-1, IL-10 and TNF- genes, are associated with CKD. 2)To determine
if the specific polymorphisms and haplotypes studied in Aim 1 are associated with faster CKD
progression and CV outcomes in a longitudinal cohort from the African American Study of
Kidney Disease. 3)To determine if a targeted anti-inflammatory intervention, an IL-1
receptor antagonist, will modulate systemic inflammation, endothelial function, oxidative
stress and urinary cytokines, the proposed surrogate markers of CVD and CKD progression in
inflame patients with CKD stages 3&4.
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Page last updated: 2013-02-10
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