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VeroScience Release: Phase IIIb Clinical Data Validate the Overall and Cardiovascular Safety Profile of Cycloset(TM) in Patients with Type 2 Diabetes



6/25/2007 10:32:20 AM

CHICAGO, Ill., June 23 /PRNewswire/ -- VeroScience, LLC, in conjunction with its commercialization partner S2 Therapeutics, Inc., reported today the results of its Phase IIIb clinical trial supporting the overall and cardiovascular safety of Cycloset(TM) (A quick release formulation of bromocriptine mesylate) in subjects with type 2 diabetes. The study, which highlighted a significant reduction in the risk of diabetic cardiovascular complications in subjects treated with Cycloset(TM) compared to placebo, also confirmed the drug's ability to improve glycemic control in subjects failing metformin plus sulfonylurea therapy.

The data were presented by the principle investigator, J. Michael Gaziano, MD, MPH, Cardiologist at Brigham and Women's Hospital and Veteran Affairs Boston Healthcare System, Boston, MA as a late-breaking poster at the 67th Scientific Sessions of the American Diabetes Association in Chicago, Ill. (June 22-26, 2007).

Cycloset(TM) is being investigated as a once-daily, timed oral therapy for type 2 diabetes that acts upon the central nervous system (CNS) to impact peripheral metabolism. The Phase IIIb trial was conducted in response to an approvable letter from the FDA requesting additional data on Cycloset(TM)'s cardiovascular safety.

The double-blind, multi-center trial's 3,070 participants included subjects with type 2 diabetes between the ages of 30 and 80 with HbA1c less than or equal to 10.0 and BMI less than or equal to 43. Participants randomized into the study were all on a treatment regimen for their diabetes, which could include either diet alone, up to two oral hypoglycemic agents, insulin alone, or insulin with no more than one oral agent. Participants were randomized in a 2:1 ratio to Cycloset(TM) (2,054 subjects; titrated from 1.6 mg/day to a maximum tolerated dose of up to 4.8 mg/day) or placebo (1,016 subjects) and followed for 52 weeks. Primary and secondary endpoints were time to first all cause serious adverse event (SAE) and cardiovascular SAE, respectively; all SAEs were adjudicated by an independent review committee.

"This cohort was selected to provide a real-world view of the safety of Cycloset(TM) in a group of patients with diabetes receiving a wide variety of diabetes regimens," said J. Michael Gaziano, MD, MPH. "We were particularly interested in assessing the potential of a cardiovascular benefit and we were excited to see that in this population and in a relatively short time period there were indications of a reduction in cardiovascular events among those treated with Cycloset(TM) compared to placebo."

The rate of any serious adverse event was similar between Cycloset(TM) subjects (8.6%) and placebo subjects (9.6%). Furthermore, fewer subjects experienced a cardiovascular endpoint in the Cycloset(TM) arm (31 out of 2,054; 1.5%) compared to the placebo arm (31 out of 1,016; 3.0%). Results of the Cox regression revealed a 43% reduction in the cardiovascular endpoint, pre-specified as the composite of myocardial infarction, stroke, and hospitalization for either angina, congestive heart failure, or coronary revascularization surgery events (hazard ratio 0.57 and 95% confidence interval of 0.34 - 0.93; P = 0.025). The most frequently observed non-serious adverse events included nausea, dizziness, and fatigue.

Participants on a combined therapy of metformin and sulfonylurea with a baseline HbA1c greater than or equal to 7.5, indicating suboptimal glycemic control (mean baseline HbA1c of 8.3), were subjected to a pre-specified secondary analysis focused on Cycloset(TM)'s ability to reduce HbA1c after 24 weeks of therapy. Those receiving Cycloset(TM) and completing 24 weeks of therapy (121 subjects) experienced a mean HbA1c reduction of 0.69 (P = 0.0002) compared to respective placebo (71 subjects) and a mean HbA1c reduction from baseline of 0.67. Moreover 39% of these Cycloset(TM) subjects, versus 11% of these placebo subjects, reached the American Diabetes Association target goal of an HbA1c level of 7.0 (P = 0.0004).

"Several decades of preclinical and clinical research have focused on investigating circadian neuroendocrine regulation of metabolism, particularly in relation to metabolic disease states such as obesity, metabolic syndrome and type 2 diabetes," said Anthony H. Cincotta, PhD, President and Chief Scientific Officer of VeroScience, LLC and a developer of Cycloset(TM) and its platform technology along with Dr. Albert H. Meier. "These study data build on our earlier investigations that suggested a beneficial impact of timed bromocriptine administration on cardiovascular risk factors apart from its influence on fasting glucose level."

"With the favorable conclusion of this large one year safety study and additional information from other clinical studies, VeroScience intends to file an amended NDA with the FDA targeting late third or fourth quarter of 2007," according to Richard E. Scranton, MD, MPH, Chief Medical Officer, VeroScience and co-principle investigator of the Cycloset(TM) Safety Trial.

Charles P. Sutphin, Co-chairman and CEO of S2 Therapeutics, Inc., holder of an exclusive global license for the manufacture, marketing, and distribution of Cycloset(TM), stated that "the commercial opportunity for Cycloset(TM) has dramatically expanded with the outcome of this trial. As a result, we are exploring strategies for Cycloset(TM)'s commercialization opportunities both within North America and globally by partnering with a large multinational pharmaceutical company."

Data presented at the 67th Scientific Sessions of the American Diabetes Association during the Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications and displayed Saturday, Sunday and Monday, June 23-25, in the General Poster Session: Poster # 50-LB, Effects of Timed Cycloset(TM) (A Quick Release Formulation of Bromocriptine Mesylate) Administration on Safety, Cardiovascular Event Rate, and Glycemic Control in Subjects with Type 2 Diabetes Receiving Diet, Oral Hypoglycemic, and/or Insulin Treatment Regimens. JM Gaziano, M Ezrokhi, AH Cincotta, RE Scranton.

About Cycloset(TM) (A Quick Release Formulation of Bromocriptine Mesylate)

Cycloset(TM) is an oral, quick-release formulation of bromocriptine, a centrally-acting dopamine D2 receptor agonist. When given as a single timed (morning) daily dose, Cycloset(TM) is believed to act on circadian neuronal activities within the hypothalamus to reset abnormally elevated hypothalamic drive for increased plasma glucose, triglyceride, and free fatty acid levels in fasting and postprandial states in insulin resistant subjects. Results of published clinical studies suggest that treatment with Cycloset(TM) may improve hyperglycemia, glucose intolerance, hyperlipidemia, or aspects of insulin resistance, while maintaining body fat neutrality or inducing body fat reduction.

Cycloset(TM) is currently under investigation as a potential therapy for type 2 diabetes and has been studied in several Phase II and three Phase III studies. An NDA for the drug's use in the treatment of type 2 diabetes has received an approvable letter from the FDA detailing the remaining data required for approval, primarily a large, simple safety trial. VeroScience anticipates filing an amended Cycloset(TM) NDA (a complete response to the approvable letter) in the late third or fourth quarter of 2007.

About VeroScience, LLC

VeroScience is a privately held biotechnology and healthcare product development company with main offices and laboratories in Tiverton, RI. VeroScience has a large patent portfolio that supports its preclinical and clinical development programs and product pipeline in the areas of metabolism, immunology, reproduction, and oncology. VeroScience leverages its intellectual property and products in out-licensing and collaborative arrangements with appropriate industry partners.

About S2 Therapeutics, Inc.

S2 Therapeutics is a specialty pharmaceutical organization, headquartered in Bristol, TN. S2 is the capital and commercialization partner for Cycloset(TM) and is holder of the exclusive global license for the manufacture, marketing and distribution of Cycloset(TM). S2 seeks opportunities in the pharmaceutical industry through in-licensing arrangements, acquisitions of novel branded prescription pharmaceutical products, and investing in development compounds and companies.

Media Contact: Feinstein Kean Healthcare Christine Cramer 617-761-6736 Cell: 508-404-6522 christine.cramer@fkhealth.com

VeroScience, LLC

CONTACT: Christine Cramer of Feinstein Kean Healthcare, +1-617-761-6736,Cell, +1-508-404-6522, christine.cramer@fkhealth.com


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