Santarus and VeroScience Announce Publication of New Analysis of CYCLOSET (bromocriptine mesylate) Cardiovascular Data in the Journal of the American Heart Association
In assessing cardiovascular safety in type 2 diabetes subjects,
CYCLOSET demonstrated a significant 52% relative risk reduction in
cardiovascular events (composite endpoint of myocardial infarction,
stroke and cardiovascular death) compared with placebo
SAN DIEGO & TIVERTON, R.I.--(BUSINESS WIRE)--
Inc. (NASDAQ: SNTS) and VeroScience, LLC today announced that new
analyses of cardiovascular endpoint data from a previously disclosed
52-week, randomized safety study with CYCLOSET®
(bromocriptine mesylate) tablets were published in the Journal of the
American Heart Association (JAHA), an online publication. CYCLOSET
is a unique, quick release form of bromocriptine, a dopamine D2 receptor
agonist, and is approved as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.
In this safety study, a total of 3,070 patients on stable doses of up to
two antidiabetes medications (including insulin) with HbA1c ≤ 10.0
(average baseline HbA1c=7.0) were randomized 2:1 to CYCLOSET (1.6 to 4.8
mg/day) or placebo for a 52-week treatment period. Patients with heart
failure (New York Heart Classes I and II) and precedent myocardial
infarction or revascularization surgery were allowed to participate in
The original prospective analysis of a prespecified cardiovascular
endpoint (composite of myocardial infarction, stroke, hospitalization
for unstable angina, congestive heart failure, or revascularization
surgery) from this study indicated a significant 40% relative risk
reduction in this cardiovascular endpoint (Diabetes Care 33:1503-1508,
The new analyses published in JAHA investigated 1) the impact of
CYCLOSET on the ischemic cardiovascular composite endpoint of myocardial
infarction, stroke, and cardiovascular death (major adverse
cardiovascular events; MACE) and 2) cardiovascular death as a component
of a new composite cardiovascular endpoint (myocardial infarction,
stroke, hospitalization for unstable angina, hospitalization for
congestive heart failure, coronary revascularization and cardiovascular
death) to more critically evaluate the impact of CYCLOSET on
cardiovascular outcomes in the study population.
Regarding the MACE endpoint, there were 14 events (0.7%) among 2,054
CYCLOSET-treated subjects and 15 events (1.5%) among 1,106
placebo-treated subjects, yielding a significant, 52% reduction in
relative risk in cumulative percent of cardiovascular events over time
of this MACE endpoint (p < 0.05; log-rank test). With respect to the
cardiovascular death-inclusive cardiovascular endpoint, there were 39
events (1.9%) among 2,054 CYCLOSET-treated subjects versus 33 events
(3.2%) among 1,016 placebo subjects, yielding a significant, 39%
reduction in relative risk in the cumulative percent over time of this
composite cardiovascular endpoint (p=0.0346; log-rank test).
These results are summarized in the table below.
n= 2054, n (%)
n= 1016, n (%)
Reduction in Events
MACE composite — myocardial
infarction, stroke, CV
CV death-inclusive composite
† p < 0.05
"Our analysis indicated that bromocriptine-QR, or CYCLOSET,
significantly reduced the cardiovascular death-inclusive composite
cardiovascular endpoint by 39% in type 2 diabetes patients after one
year of treatment. Importantly, this observed relative risk reduction
was consistent regardless of age, race, sex, duration of disease or
preexisting macrovascular disease," said J. Michael Gaziano, M.D.,
Chief, Division of Aging, Brigham and Women's Hospital, Professor of
Medicine, Harvard Medical School, and lead author of the article.
"Furthermore, among patients in the study, CYCLOSET significantly
reduced the relative risk for the composite cardiovascular endpoint of
myocardial infarction, stroke and cardiovascular death by 52%."
The article, titled Effect of Bromocriptine-QR (a Quick-Release
Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular
Events in Type 2 Diabetes Subjects can be found online at http://jaha.ahajournals.org/content/1/5/e002279.
Important Safety Information
CYCLOSET is a dopamine receptor agonist indicated as an adjunct to diet
and exercise to improve glycemic control in adults with type 2 diabetes
CYCLOSET is contraindicated in:
Patients with known hypersensitivity to bromocriptine, ergot-related
drugs, or any of the excipients in CYCLOSET.
Patients with syncopal migraine. Bromocriptine increases the
likelihood of a hypotensive episode among patients with syncopal
migraine. Loss of consciousness during a migraine may reflect dopamine
receptor hypersensitivity. CYCLOSET is a dopamine receptor agonist,
and may, therefore, potentiate the risk for syncope in these patients.
Women who are nursing their children. CYCLOSET may inhibit lactation.
There are postmarketing reports of stroke in this patient population
although causality has not been proven.
Warnings and Precautions
Hypotension: Can cause orthostatic hypotension and syncope,
particularly upon initiation or dose escalation. Use caution in
patients taking anti-hypertensive medications. Assess orthostatic
vital signs prior to initiation of CYCLOSET and periodically
thereafter. Advise patients during early treatment to avoid situations
that could lead to injury if syncope was to occur.
Psychosis: May exacerbate psychotic disorders or reduce the
effectiveness of drugs that treat psychosis. Use in patients with
severe psychotic disorders is not recommended.
Somnolence: May cause somnolence. Advise patients not to operate heavy
machinery if symptoms of somnolence occur.
Interaction with dopamine antagonists: Concomitant use with dopamine
antagonists such as neuroleptic agents may diminish the effectiveness
of both drugs. Concomitant use is not recommended.
Other dopamine receptor agonists: Effectiveness and safety are unknown
in patients already taking dopamine receptor agonists for other
indications. Concomitant use is not recommended.
Macrovascular outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with
CYCLOSET or any other antidiabetic drug. CYCLOSET does not increase
the risk of macrovascular events.
In controlled clinical trials, adverse reactions reported in ≥5% of
patients treated with CYCLOSET and reported more commonly than in
patients treated with placebo, included nausea, fatigue, dizziness,
vomiting, and headache.
Postmarketing reports with higher doses of bromocriptine used for other
indications include psychotic disorders, hallucinations, and fibrotic
May increase the unbound fraction of highly protein-bound therapies,
altering their effectiveness and safety profiles.
May increase ergot-related side effects or reduce ergot effectiveness
for migraines if co-administered within 6 hours of ergot-related drugs.
Extensively metabolized by CYP3A4. Use caution when co-administering
strong inhibitors, inducers, or substrates for CYP3A4.
The Important Safety Information does not include all the information
needed to use CYCLOSET safely and effectively. See Full Prescribing
Information for CYCLOSET for additional information, available at www.cycloset.com
or by contacting Santarus at (888) 778-0887.
VeroScience is a privately held biotechnology and healthcare product
development company with main offices and laboratories in Tiverton, R.I.
VeroScience holds the New Drug Application and related technology for
CYCLOSET and has a large patent portfolio that supports its preclinical
and clinical development programs and product pipeline in the areas of
metabolism, immunology and oncology. VeroScience leverages its
intellectual property and products in out-licensing and collaborative
arrangements with appropriate industry partners.
Santarus, Inc. is a specialty biopharmaceutical company focused on
acquiring, developing and commercializing proprietary products that
address the needs of patients treated by physician specialists. The
company's current commercial efforts are focused on GLUMETZA®
(metformin hydrochloride extended release tablets) and CYCLOSET®
(bromocriptine mesylate) tablets, which are indicated as adjuncts to
diet and exercise to improve glycemic control in adults with type 2
diabetes, and on FENOGLIDE®
(fenofibrate) tablets, which is indicated as an adjunct to diet to
reduce high cholesterol. Santarus also sells ZEGERID®
(omeprazole/sodium bicarbonate), which is indicated for the treatment of
certain gastrointestinal diseases and disorders.
Santarus has a diverse product development pipeline. A New Drug
Application for UCERIS™ (budesonide) for induction of
remission of active, mild to moderate ulcerative colitis is under review
by the U.S. Food and Drug Administration with a response expected in
January 2013. The pipeline also includes two late-stage investigational
drugs in Phase III clinical studies: RUCONEST® (recombinant
human C1 esterase inhibitor) for treatment of acute attacks of
hereditary angioedema and rifamycin SV MMX® for treatment of
travelers' diarrhea. In addition, the company's investigational
monoclonal antibody, SAN-300, is being evaluated in a Phase I clinical
program. More information about Santarus is available at www.santarus.com.
Santarus cautions you that statements included in this press release
that are not a description of historical facts are forward-looking
statements. The inclusion of forward-looking statements should
not be regarded as a representation by Santarus that any of its plans or
objectives will be achieved. Actual results may differ materially
from those set forth in this release due to the risks and uncertainties
inherent in Santarus' business, including, without limitation: risks
associated with the collaboration relating to CYCLOSET, including the
potential for termination of the collaboration; competition from other
products; unexpected adverse side effects or inadequate therapeutic
efficacy of Santarus' products and product candidates; the scope and
validity of patent protection for Santarus' products and product
candidates; and other difficulties or delays relating to the
development, testing, manufacturing and marketing of, and obtaining and
maintaining regulatory approvals for, Santarus' products and product
candidates; and other risks detailed in Santarus' prior press releases
as well as in prior public periodic filings with the Securities and
You are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof. All
forward-looking statements are qualified in their entirety by this
cautionary statement and Santarus undertakes no obligation to revise or
update this news release to reflect events or circumstances after the
date hereof. This caution is made under the safe harbor
provisions of Section 21E of the Private Securities Litigation Reform
Act of 1995.
UCERIS™ and ZEGERID®
are trademarks of Santarus, Inc. GLUMETZA®
is a trademark of Biovail Laboratories International S.r.l. licensed
exclusively in the United States to Depomed, Inc. CYCLOSET®
is a trademark of VeroScience LLC. MMX®
is a trademark of Cosmo Technologies Limited.
RUCONEST® is a trademark of Pharming Group
Martha L. Hough
VP Finance & Investor
Debra P. Crawford
Westwicke Partners, LLC
H. Cincotta, Ph.D.
President and Chief Scientific Officer
Source: Santarus, Inc.
News Provided by Acquire Media
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