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Lupus Clinical Trials

New Medical Therapies™

Angina

September 3, 2007

Cardium reported mixed results from two phase IIb/III trials of Generx for the treatment of chronic angina. These randomized, double-blind, placebo-controlled trials were dubbed AGENT (Angiogenic GENe Therapy -3 and -4 and enrolled a total of 532 subjects in the US and Europe. Subjects received a low dose or high dose of Generx, administered via intracoronary infusion or placebo for 12 weeks. The primary endpoint was the change from baseline in exercise treadmill time (ETT) at 12 weeks and at secondary time points of 4 weeks and 6 months. Secondary endpoints included time to 1 mm ST-segment depression, time to onset of angina and change in Canadian Cardiovascular Society (CCS) class. Pooled data showed no significant difference in the active groups versus placebo in the primary endpoint. There was a large and significant placebo effect compared with baseline, which persisted over 6 months. In addition, none of the secondary endpoints were achieved with the exception of change in CSS class; significant improvement over placebo only for the high-dose group was observed at week 12, month 6, and month 12 (p< 0.05). However, in a pooled analysis of pre-specified subgroups statistically significant results were seen among women in all the primary and secondary endpoints as compared to placebo. These were observed at both the three and six month evaluation endpoints for the high dose group (p less than 0.01 to p less than 0.05). In addition, treatment with the low dose of Generx showed statistically significant results over placebo in ETT at three and six months, time to ST-segment depression at six months, and CCS Class at twelve months (p less than 0.05). Based on the results, Cardium created an FDA approved adjusted clinical protocol and is currently conducting a phase III study in women with angina.

March 14, 2005

Corautus Genetics reported two-year follow-up results of a phase I train of a phase I study of VEGF-2 plasmid DNA gene therapy, for the treatment of severe angina. Trial data demonstrated significant preliminary efficacy, with subjects experiencing a significant mean decrease in angina class (a measure of symptom severity) from 3.6 +/- 0.5 at baseline to 1.3 +/- 1.0 at 12 months and 1.5 +/- 1.2 at 24 months (p < 0.05). Safety data for the treatment were generally positive, with overall risk of death and serious cardiovascular events consistent with those associated with underlying advanced atherosclerosis, the condition giving rise to these subjects’ angina; the incidence of these events was low during the first 12 months, but increased through month 24. This open-label, multi-center trial enrolled 30 patients with advanced (Class III or IV) treatment-refractory angina with multivessel occlusive coronary artery disease; subjects received one of three single doses of the drug (200, 800 or 2,000 micrograms), then were followed for 24 months. These data went to support an ongoing phase IIb trial of the drug.

February 7, 2005

Speedel Pharma announced positive results from phase I studies a pair of their investigational rennin inhibitors, SPP630 and SPP635, for the treatment of hypertension and protection of end-organs including the heart and kidneys. Data from the trials met pharmacokinetic endpoints, establishing a bio-availability of roughly 30%, an elimination half-life of more than 30 hours (suitable for once daily dosing), and an improved tissue distribution profile. These micro-dosing studies of both drugs used nano-molar doses to investigate their pharmacokinetics in healthy volunteers. Speedel announced that the completion of these trials allowed for the initiation of expanded, classical phase I studies in Q3, 2005.

October 25, 2004

deCODE genetics issued positive preliminary results of a phase IIa trial of DG031, their investigational cardioprotective for the prevention of heart attack. Trial data met their primary efficacy endpoint, demonstrating a significant reduction in one or more biomarkers of heart attack, in at-risk patients. This included a significant reduction of leukotriene B4 at all investigational doses, and significant reductions of MPO and sICAM-I at the highest investigational dose, compared with placebo. No serious tolerability concerns were raised, though one myocardial infarction occurred in the active drug group and one sudden death occurred in a subject receiving placebo. This double-blind, placebo-controlled, dose-escalating crossover study enrolled 172 subjects with a history or a genetic predisposition to heart attack.

Liponex has issued preliminary results from a phase I trial of CRD5, for the treatment hypercholesterolemia and atherosclerosis. Data from the trial showed that drug was safe and well tolerated with no adverse reactions reported, meeting their primary endpoint. In addition, secondary efficacy data indicated that the drug showed significant efficacy in both increasing HDL (good) cholesterol (18% over baseline) and reducing LDL (bad) cholesterol (15%-60% from baseline). This open-label study enrolled 56 healthy volunteers, who received CRD5 for two weeks. Based upon these results, Liponex announced plans to initiate phase II trials of CRD5 in 2005.

Vertex Pharmaceuticals reported preliminary results from a phase IIa trial of VX-702, their investigational p38 MAP kinase inhibitor, for the treatment of acute coronary syndrome in patients undergoing percutaneous coronary intervention. Study results indicate that the drug met its primary safety and pharmacokinetic endpoints, with no significant increase in adverse events compared with placebo, and no significant difference in incidence of liver enzyme abnormalities. The drug also met its secondary efficacy endpoints, significantly reducing serum C-reactive protein (CRP) levels up to 48 hours after treatment in all dosing cohorts compared with placebo. This double-blind, placebo-controlled dose escalation study enrolled a total of 45 patients with unstable angina and acute coronary syndrome. Subjects were randomized to receive one of four doses of the drug or placebo once daily for five days, prior to PCI intervention.

April 26, 2004

CV Therapeutics reported results from a phase III trial investigating Ranexa (ranolazine), a pFOX inhibitor for the treatment of angina. Results demonstrated a statistically significant increase in symptom-limited exercise duration at trough drug concentrations, the studies primary endpoint. Data showed a statistically significant increase in the time to onset of angina pain during exercise testing and exercise time in subjects receiving Ranexa. Specific dose-related adverse events included dizziness, nausea, asthenia and constipation. The double-blind, placebo-controlled, randomized study, called MARISA, enrolled 191 subjects with angina not receiving any other anti-anginal medications. Subjects receive Ranexa (500, 1000 and 1500 mg) or placebo twice a day. Results were reported in an April issue of the Journal of the American College of Cardiology.

Forbes Medi-Tech reported additional data from a European phase II trial investigating FM-VP4, an analogue of phytostanols for the treatment of high cholesterol. Results showed that FM-VP4 demonstrated a statistically significant dose-response, suggesting that 400 mg/day may be the optimal dose. Data revealed that LDL cholesterol levels might continue to decrease if FM-VP4 was administered for longer than 4 weeks. Analysis also showed a need to examine the effects of timing of FM-VP4 with respect to food intake and efficacy. Complete results are anticipated in June of 2004.

April 14, 2003

CV Therapeutics reported positive sub-analysis results from a phase III trial investigating Ranexa (ranolazine), a fatty acid oxidation inhibitor for the treatment of angina. Results demonstrated that Ranexa increased exercise duration and time to onset of angina similarly in both diabetic and non-diabetic subjects. Ranexa also reduced glycated hemoglobin (HbA1c) levels in diabetic subjects by an average of 0.7 percentage points in subjects not taking insulin and 1.1 percentage points in subjects taking insulin. Percentage points correlated to the amount of glycated hemoglobin in the blood. The randomized, double blind, placebo-controlled trial called CARISA (Combination Assessment of Ranolazine In Stable Angina) enrolled 823 subjects (183 with diabetes) to test Ranexa in chronic angina subjects also receiving a background anti-anginal medication.

March 18, 2002

Phase II trial results indicate that Ad5FGF-4 improves myocardial perfusion in subjects with moderate to severe exertional angina. In the double-blind trial, 52 subjects were randomized to receive either a one-time administration of Ad5FGF-4 or placebo by intracoronary infusion into the left and right coronary systems. Results showed that at eight weeks post-treatment, worsening of myocardial perfusion occurred in 35% of subjects receiving placebo versus 6% of subjects treated with Ad5FGF-4. Additionally, 51% of subjects receiving Ad5FGF-4 experienced a greater than or equal to 5% reduction in their stress-related reversible myocardial perfusion defect size, compared to 35% of placebo-treated subjects. Ad5FGF-4 is being developed by Berlex Laboratories and Collateral Therapeutics.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.