Results Of Trials In Diabetic Patients With Cardiovascular Disease
Synvista Therapeutics announced data from three Phase 2 trials (Trials 201a, 201 and 203) of SYI-2074 in Type 2 diabetic patients. Trial 201a established that haptoglobin (Hp) types, the target of Synvista's proprietary haptoglobin variant test currently under development, correlated with a difference in baseline levels of plasma isoprostanes, confirming that Hp2-2 in diabetic patients is associated with increased oxidized lipids. The mean F2a isoprostane level in Hp2-2 diabetic patients was 632 ng/mg Cr and in Hp1-1 diabetic patients was 453 ng/mg Cr (p=0.001).
Trial 201 showed that SYI-2074, in Hp2-2 diabetic patients, did not demonstrate a dose-related improvement in all oxidized lipids and all markers of oxidative stress after one month. In Trial 203, SYI-2074 did not provide evidence of protection against cardiac injury in diabetic patients who were undergoing angioplasty. The Company has therefore decided not to advance the development of SYI-2074 as a treatment for acute coronary syndrome, while it continues to review and analyze the results of these studies.
These Phase 2 results do not impact the Company's plans to test a topical formulation of SYI-2074 in plaque psoriasis. Synvista expects to begin enrollment of patients with mild-to-moderate plaque psoriasis in a Phase 2 trial in the third quarter of 2008, as originally planned. The Company is continuing to evaluate a series of back-up compounds to SYI-2074 in preclinical studies, on the basis of some of the signals in these trials. The Company hopes to provide an update on this program during the third quarter of 2008.
"We are choosing not to advance the SYI-2074 program in the very competitive area of acute coronary syndrome at this time, in the absence of stronger surrogate markers of efficacy," said Noah Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Synvista Therapeutics.
"We are pleased to have established correlation between increased plasma isoprostanes and haptoglobin type, as we believe this further validates the biology underlying our proprietary haptoglobin test. Haptoglobin typing has been used in studies that have evaluated more than 20,000 patients, and researchers have demonstrated that Hp2-2 patients with diabetes are at high risk for myocardial infarction, heart failure and stroke. To that end, our diagnostic test is on track to be available commercially in the second quarter of 2009. Further, we are planning to submit a kit measuring CML (carboxy-methyl-lysine), another increasingly well-validated, cardiovascular biomarker, for FDA marketing clearance in 2009," Dr. Berkowitz continued. "We are also moving forward with our alagebrium program, which began enrollment last month in a Phase 2 study for diastolic heart failure in Haptoglobin 2-2 diabetic patients, which complements a second Phase 2 study in systolic heart failure, begun last November and almost half enrolled."
About the Studies
Trial 201 was a Phase 2, placebo-controlled, dose-escalation study in which patients with diabetes and Hp2-2 were given SYI-2074 at 20, 40 or 80mg or placebo three times daily for 28 days. The study evaluated the impact of these doses on inflammatory biomarkers, and the quality and quantity of their cholesterol. Results found that SYI-2074 demonstrated improvement in some but not all of these biomarkers.
Trial 201a was a Phase 2, placebo-controlled sub-study of Trial 201. Patients with diabetes, meeting enrollment criteria for Trial 201 were tested for haptoglobin type. Patients with Hp2-2 or Hp1-1 were evaluated for baseline levels of plasma and urinary isoprostanes, CRP, myeloperoxidase, paraoxonase and other markers of inflammation or oxidative stress.
Trial 203 was a Phase 2, placebo-controlled study evaluating 40mg of SYI-2074 administered three times daily for two days in diabetic patients undergoing angioplasty. The primary endpoint of the study was reduction of the amount of heart muscle enzyme (CK-MB) released from the heart as a consequence of the procedure. Results showed that there was no significant reduction in CK-MB, which indicates that the normal damage to heart muscle following an angioplasty occurred during the procedure regardless of the administration of SYI-2074.