Santarus and VeroScience Announce Publication of Positive Data from Pivotal
CYCLOSET® (bromocriptine mesylate) Efficacy Study
CYCLOSET add-on therapy provided significant improvement in glycemic control
versus placebo in patients with type 2 diabetes poorly controlled on one or
two oral anti-diabetes medications
SAN DIEGO & TIVERTON, R.I. -- January 23, 2013
Santarus, Inc. (NASDAQ: SNTS) and VeroScience, LLC today announced publication
of positive data from a double-blind, placebo-controlled, multi-center pivotal
study with CYCLOSET^® (bromocriptine mesylate) tablets. Patient groups in the
evaluable per protocol (EPP) population that added CYCLOSET to their treatment
regimen achieved a 0.60% to 0.70% reduction in HbA1c (p<0.0001) relative to
placebo after 24 weeks, the primary endpoint of the study. These results
appear in the November/December 2012 print edition of Endocrine Practice, a
peer-reviewed medical journal.
Additionally, among the EPP population with no concomitant change in diabetes
medication, treatment with CYCLOSET resulted in:
*Reductions in HbA1c levels of 0.69% to 0.83% (CYCLOSET vs. placebo between
group difference, p<0.0001)
*Five to seven times more subjects reaching the goal of HbA1c ≤7.0 in the
CYCLOSET treated groups compared with placebo (32%-42% vs 5%-7%,
CYCLOSET is a unique, quick release form of bromocriptine, a dopamine receptor
agonist that is approved as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus. The study included
515 patients with type 2 diabetes with baseline HbA1c of ≥7.5% and ≤10.0%
(average baseline HbA1c: 8.3) taking one or two oral anti-diabetes medications
(metformin, sulfonylurea and/or thiazolidinediones). These poorly controlled
patients were randomized 2:1 to CYCLOSET add-on (1.6 mg/day to 4.8 mg/day) or
placebo add-on for a 24-week treatment period. Study investigators were
allowed to adjust patient anti-diabetes medications during the study to
attempt to achieve glycemic control in case of glycemic deterioration. The
impact of CYCLOSET treatment was assessed in patients taking: (1) one or two
oral anti-diabetes medications, (2) metformin with or without another oral
anti-diabetes medication, or (3) metformin plus a sulfonylurea. The study was
conducted in a cohort of patients imbedded in a larger randomized safety
The results of the primary endpoint analysis for the intent-to-treat (ITT) and
EPP populations are summarized in the table below.
Effect of CYCLOSET Versus Placebo on Change from Baseline HbA1c (%)^a
and Odds Ratio of Achieving Goal of HbA1c ≤ 7.0
ITT EPP EPP
Any one or two oral No concomitant
medications in diabetes
N=515 N=379 N=272
Between group -0.51 -0.60 -0.69 (-0.97,
difference HbA1c (-0.70, (-0.83, -0.41)^b
Odds ratio of 3.48 (1.96, 5.80 (2.93, 6.50 (2.67,
achieving HbA1c ≤ 7.0 6.18)^b 11.47)^b 15.84)^b
ITT EPP EPP
Metformin with or No concomitant
without another change
oral anti-diabetes in diabetes
N=356 N=262 N=198
Between group -0.56 -0.68 -0.81 (-1.12,
difference HbA1c (-0.78, (-0.93, -0.51)^b
Odds ratio of 3.98 (1.98, 6.69 (2.98, 12.03 (3.53,
achieving HbA1c ≤ 7.0 7.98)^b 15.04)^b 40.99)^b
ITT EPP EPP
Metformin plus a No concomitant
N=245 N=179 N=129
Between group -0.49 -0.70 -0.83 (-1.18,
difference HbA1c (-0.75, (-1.00, -0.48)^b
Odds ratio of 3.77 (1.72, 7.26 (2.92, 11.45 (3.19,
achieving HbA1c ≤ 7.0 8.30)^d 18.01)^c 41.12)^c
^aValues are based on mean (95% Confidence Interval), adjusted by baseline
^bp < 0.0001
^cp < 0.0002
^dp < 0.001
The most frequent adverse events in the study for CYCLOSET and placebo were,
respectively, nausea (33% vs. 6%), fatigue (11% vs. 8%), dizziness (14% vs.
11%), headache (12% vs. 8%), constipation (7% vs. 3%), back pain (6% vs. 3%)
and vomiting (6% vs. 2%). The discontinuation rate due to any adverse event
was 20% for CYCLOSET-treated and 9% for placebo-treated patients.
“The results of this pivotal study show that the addition of CYCLOSET to the
treatment regimen in this poorly controlled type 2 diabetes patient population
produces significant and clinically relevant improvements in glycemic control
markedly increasing the percent of patients reaching the HbA1c goal of ≤ 7.0
vs. placebo,” stated Aaron I. Vinik, M.D., Ph.D, Strelitz Diabetes Center and
Neuroendocrine Unit, Norfolk, Virginia and lead author of the paper.
The article, titled Effect of Bromocriptine-QR on Glycemic Control in Subjects
with Uncontrolled Hyperglycemia on One or Two Oral Anti-Diabetes Agents can be
found online at http://www.ncbi.nlm.nih.gov/pubmed/23186965.
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 mellitus.
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
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
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. In March 2013, the company
plans to begin promoting UCERIS^™ (budesonide) extended release tablets for
the induction of remission of active, mild to moderate ulcerative colitis and
ZEGERID^® (omeprazole/sodium bicarbonate) for the treatment of certain upper
gastrointestinal disorders. Safety information and full prescribing
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 first half of 2013. Santarus is also developing rifamycin SV
MMX^®, which is in Phase III clinical testing for treatment of travelers’
diarrhea. In addition, SAN-300, the company’s investigational monoclonal
antibody, is in Phase I clinical testing. 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 Exchange
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.
Santarus^®, FENOGLIDE^®, 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 & Investor Relations
Debra P. Crawford
Chief Financial Officer
Westwicke Partners, LLC
Stefan Loren, Ph.D., 858-356-5930
Robert Uhl, 858-356-5932
Anthony H. Cincotta, Ph.D.
President and Chief Scientific Officer
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