Santarus and VeroScience Announce Publication of AACE Expert Panel Recommendations for CYCLOSET® (bromocriptine mesylate) for the Management of Type 2 Diabetes

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 disease

SAN DIEGO & TIVERTON, R.I.--(BUSINESS WIRE)--Santarus, 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 recommendations:

• 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 publication.

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 anti-diabetes 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 [phone].

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 five products. UCERIS^™ (budesonide) extended release tablets for the induction of remission in patients with active, mild to moderate ulcerative colitis and ZEGERID^® (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 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.