Another peace of evidence that there is room for optimism.
51% versus 35% (why this high numbers for placebo???) and primary end-point was not significant, but two other end-point show trend toward real medical benefit.
Miljenko
Friday March 8, 9:02 am Eastern Time
Press Release
SOURCE: Schering AG Germany and Collateral Therapeutics
Gene Therapy Product Candidate Ad5FGF-4 Shows Improvement in Myocardial Perfusion in an Exploratory Phase II Study
BERLIN, and SAN DIEGO, March 8 /PRNewswire-FirstCall/ -- Schering AG (NYSE: SHR; FSE: SCH), its US affiliate Berlex Laboratories, Inc. and Collateral Therapeutics, Inc. (Nasdaq: CLTX - news), announce results from a Phase II double-blind, placebo-controlled study demonstrating that their product candidate Ad5FGF-4 showed improvement in myocardial perfusion (blood flow to the heart) in patients with moderate to severe exertional angina. Ad5FGF-4 is an angiogenic gene therapy product that is being developed for the treatment of patients with stable exertional angina due to coronary artery disease.
``We are encouraged by these results and will vigorously pursue our clinical development program for the product, that includes two large-scale multi-center Phase IIb/III studies, one in the United States, that is ongoing, and the other in Europe, where patient enrollment is slated to begin shortly,'' said Dr. Joachim-Friedrich Kapp, Head of Schering AG, Germany's strategic business unit, Specialized Therapeutics.
``Last year, our successful Phase I/II clinical trial provided important safety and preliminary efficacy information about Ad5FGF-4 in patients with mild to moderate angina, this new study provides additional evidence of safety in patients with moderate to severe angina, coupled with evidence of an improvement in myocardial perfusion in these patients,'' reported Jack W. Reich, Ph.D. chairman and chief executive officer of Collateral Therapeutics. ``Taken together, the positive findings from these two studies fully support the advancement of Ad5FGF-4 into large-scale Phase IIb/III clinical studies in both the U.S. and in Europe.''
Fifty-two patients were randomized in this exploratory study to receive either a one-time administration of Ad5FGF-4 (35 patients) or placebo (17 patients) via intracoronary infusions into the left and right coronary systems. To participate in the trial, patients had to have moderate to severe exertional angina despite being on antianginal medicine. The majority of patients in the study had previous coronary artery bypass surgery and/or angioplasty. Changes in blood flow in different regions of the heart were evaluated by radionuclide perfusion images obtained at rest and after adenosine administration. These images were used to evaluate rest and stress-related (reversible) perfusion defect size prior to treatment and four and eight weeks post-treatment. Patients continued to receive their antianginal medications during the study.
The product candidate, Ad5FGF-4 was well tolerated and appeared safe in this study population which had more severe angina than the population studied in the AGENT Phase I/II study. In the AGENT Phase I/II study, Ad5FGF-4 was shown to be safe and well tolerated, and to have a favorable effect on exercise tolerance. No deaths or myocardial infarctions were reported during post-treatment follow-up extending up to six months.
The mean reversible perfusion defect size at 8 weeks post-treatment, which was the primary endpoint, was reduced by 21% of the baseline value in patients receiving Ad5FGF-4 versus 8% in patients receiving placebo. While the primary end point of this Phase II study did not quite reach statistical significance, the analysis was confounded by an unusually high degree of change in a single placebo outlier.
Among the positive observations seen in this study were:
* Worsening of myocardial perfusion (defined as greater than or equal to
4% absolute increase in reversible perfusion defect size) at 8 weeks
post-treatment occurred in 35% of patients receiving placebo and only
6% of patients receiving Ad5FGF-4, which was statistically significant.
* Three patients who received Ad5FGF-4 and who experienced a reduction in
their stress-related perfusion defect size, also experienced a similar
reduction in their resting or "non-reversible" perfusion defect size.
These results are consistent with an increase in blood supply to a
"hibernating" portion of the heart (an area of the heart with little
blood supply and little or no contractility).
* 51% of patients receiving Ad5FGF-4 experienced a greater than or equal
to 5% reduction in their stress-related reversible myocardial perfusion
defect size as compared to 35% of patients receiving placebo, after
eight weeks post treatment.
About Ad5FGF-4
Angiogenesis with Ad5FGF-4 is designed to stimulate new blood vessel growth which may provide alternate routes for blood to flow into oxygen-deprived ischemic areas of the heart due to blocked or narrowed arteries. Envisioned as a procedure that could be administered by interventional cardiologists, Ad5FGF-4 involves a one-time administration of an adenoviral gene therapy vector containing the human Fibroblast Growth Factor 4 (FGF4) angiogenic gene delivered into the coronary arteries through a standard catheter.
About Coronary Artery Disease
Angina is chest pain caused by myocardial ischemia, a condition in which the amount of oxygen the heart muscle requires exceeds the amount available due to coronary artery blockage (atherosclerosis). According to the American Heart Association (AHA), angina affects approximately 6.4 million Americans, with 400,000 new cases of stable angina diagnosed each year. Angina is a symptom of coronary artery disease (CAD) which is a leading cause of death in the United States. Current treatment options for CAD include drug therapy or revascularization procedures, including angioplasty and bypass surgery. According to the AHA, approximately 600,000 angioplasties and nearly 570,000 bypass surgeries are performed each year in the United States. <snip> |
