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)--Nov 13, 2012 - Santarus, 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 trial.

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, 2010).

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.

 

 

    Cycloset
n= 2054, n (%)

 

 

    Placebo
n= 1016, n (%)

 

 

    Cumulative Percent
Reduction in Events
Over Time

 

MACE composite – myocardial
infarction, stroke, CV death

 

    14 (0.7)     15 (1.5)     52% 
CV death-inclusive composite
cardiovascular endpoint

 

    39 (1.9)     33 (3.2)     39%*
  p<0.05

 

* p=0.0346

 

                   
“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 mellitus.

Contraindications

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.

Adverse Reactions

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 complications.

Drug Interactions

 

  • 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.

About VeroScience

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.

About Santarus

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 Exchange Commission.

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.

Contact: Santarus, Inc.
Martha L. Hough
VP Finance & Investor Relations
858-314-5824
or
Debra P. Crawford
Chief Financial Officer
858-314-5708
or
Westwicke Partners, LLC
Stefan Loren, Ph.D.
858-356-5930
sloren@westwicke.com
or
Robert Uhl
858-356-5932
robert.uhl@westwicke.com
or
VeroScience
Anthony H. Cincotta, Ph.D.
President and Chief Scientific Officer
401-816-0525

 

Posted: November 2012

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