Experts conclude that favorable cardiovascular profile of CYCLOSET
suggests it may be useful in the treatment of patients with type 2
diabetes with significant risk factors or history of cardiovascular
SAN DIEGO & TIVERTON, R.I. -- (Business Wire)
Inc. (NASDAQ: SNTS) and VeroScience, LLC today announced publication
of a review article and recommendations of an American Association of
Clinical Endocrinologists (AACE) expert panel on the role of
bromocriptine-QR in the management of type 2 diabetes. The panel
concluded that treatment with CYCLOSET® (bromocriptine
mesylate), also referred to as bromocriptine-QR, may be useful in the
treatment of patients with type 2 diabetes, both early and late in the
life cycle of the disease, and especially for patients with a history of
cardiovascular disease or who have significant risk factors for
cardiovascular disease. The article, titled The Role of
Bromocriptine-QR in the Management of Type 2 Diabetes Expert Panel
Recommendations will appear in print form in the January/February
issue of Endocrine Practice, a peer-reviewed medical journal published
by AACE, and can be found in the online edition of the journal at http://aace.metapress.com/home/main.mpx.
The expert panel also made the following observations and
CYCLOSET has a novel mechanism of action that appears to involve
enhancement of morning central nervous system dopaminergic activity,
which is reduced in obese individuals with type 2 diabetes. This
improvement can potentially lead to improved insulin sensitivity and
reduced hepatic glucose output.
Adjunctive administration of CYCLOSET in the dosing range of 1.6
mg/day to 4.8 mg/day may result in a mean reduction in A1c levels of
0.69% (95% Confidence Interval: 0.97%, 0.41%).
A 24-week completer analysis performed among efficacy subgroups of
patients from the CYCLOSET safety study stratified based on the
patient’s baseline A1c levels (≥7.5 to <8.0 versus 8.0 to 8.5
versus ≥8.5).(Vinik et al, Endo. Practice Vol18, p 931-943, 2012)
yielded the following results: in the subgroup treated with
metformin (with or without another oral hypoglycemic agent),
treatment with bromocriptine-QR was associated with a
significantly higher proportion of subjects achieving a Week 24
A1c level ≤7 compared with placebo when baseline A1c levels were
≥7.5 to <8.0 or 8.0 to 8.5 (47% versus 4% and 42% versus 6%,
respectively). In the subgroup treated with metformin and a
sulfonylurea agent, treatment with bromocriptine-QR was also
associated with a significantly higher proportion of patients
achieving a Week 24 A1c level ≤7 compared with placebo when
baseline A1c levels were ≥7.5 to <8.0 or 8.0 to 8.5 (57% versus 5%
and 46% versus 8%, respectively).
Improvement in glycemic control during adjunctive treatment with
CYCLOSET is achieved with minimal intrinsic risk of hypoglycemia and
without clinically significant adverse effects on weight,
triglycerides, free fatty acids or blood pressure.
The large (n=3,070) placebo-controlled 12-month safety study provides
the most detailed and systematic information on the long-term
tolerability of CYCLOSET in the treatment of type 2 diabetes. Nausea
was the most common adverse event (32.2%), and was associated with
premature study discontinuation in 7.6% of patients. Other adverse
events occurring with an incidence of at least 10% were dizziness
(14.8%), fatigue (13.9%), and headache (11.4%). The incidence of
nausea was similar in short-term placebo-controlled trials when
CYCLOSET was used as a monotherapy (32.5%) or when it was used as an
adjunctive therapy with sulfonylurea (25.4%).
The major limitation to the use of CYCLOSET is the relatively small
clinical trials database. As a result, there is currently insufficient
information on the safety and efficacy of adjunctive therapy with
CYCLOSET in type 2 diabetes patients being treated with other diabetes
regimens such as thiazolidinediones or insulin.
CYCLOSET’s novel mechanism of action and favorable cardiovascular risk
profile may make it a useful addition to the spectrum of agents
available to treat type 2 diabetes.
The members of the expert panel were:
Alan J. Garber, MD, PhD, Departments of Medicine, Biochemistry and
Cell Biology, Baylor College of Medicine, Houston, Texas;
Lawrence Blonde, MD, FACP, FACE, Ochsner Diabetes Clinical Research
Unit, Department of Endocrinology, Diabetes and Metabolism, Ochsner
Medical Center, New Orleans, Louisiana;
Zachary T. Bloomgarden, MD, Department of Medicine, Mount Sinai School
of Medicine, New York City, New York;
Yehuda Handelsman, MD, FACP, FACE, Metabolic Institute of America,
Tarzana, California; and
Samuel Dagogo-Jack, MD, Division of Endocrinology, Diabetes and
Metabolism and Clinical Research Center, University of Tennessee
Health Science Center, Memphis, Tennessee.
Financial support for the AACE expert panel workshop was provided by
Santarus through an independent grant. Santarus did not participate in
or have any influence on the AACE panel workshop, recommendations or
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 anti-diabetes 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 five products. UCERIS™(budesonide) extended release tablets for the induction of
remission in patients with active, mild to moderate ulcerative colitis
(omeprazole/sodium bicarbonate) for the treatment of certain upper
gastrointestinal disorders are promoted to gastroenterologists. 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 FENOGLIDE®
(fenofibrate) tablets, which is indicated as an adjunct to diet to
reduce high cholesterol, are promoted to endocrinologists and other
physicians who treat patients with type 2 diabetes. Full prescribing and
safety information for Santarus’ products are available at www.santarus.com.
Santarus’ product development pipeline includes the investigational drug
RUCONEST® (recombinant human C1 esterase inhibitor) for
treatment of acute attacks of hereditary angioedema. The company expects
to submit a biologics license application (BLA) to the U.S. Food and
Drug Administration for RUCONEST in the second quarter of 2013. Santarus
is also developing rifamycin SV MMX®, which is in Phase III
clinical testing for treatment of travelers’ diarrhea. In addition, the
company has completed a Phase I clinical program with SAN-300, an
investigational monoclonal antibody. 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 N.V.
Martha L. Hough
VP Finance &
Debra P. Crawford
Westwicke Partners, LLC
Loren, Ph.D. (firstname.lastname@example.org)
Anthony H. Cincotta, Ph.D.
President and Chief
Source: Santarus, Inc.
© 2014 Canjex Publishing Ltd. All rights reserved.