Collateral Therapeutics Inc.'s angiogenic gene therapy, Ad5-FGF4, appeared safe and well tolerated, not to mention efficacious, in treatment of patients with stable exertional angina due to coronary artery disease.
The dose-escalating, double-blind, placebo-controlled, Phase I/II trial evaluated the safety and anti-ischemic effects of five dose levels of Ad5-FGF4 in 79 patients and identified potential safe and effective doses for further study.
Results were presented Monday at the 50th Annual Scientific Session of the American College of Cardiology in Orlando.
Ad5-FGF4 is composed of an adenoviral gene therapy vector containing the human fibroblast growth factor-4 angiogenic gene, which replaces the E1A/E1B genes in a replication-deficient serotype 5 adenovirus. It entails a single nonsurgical administration and is designed to stimulate blood vessel formation.
Fifty percent of patients treated with a certain dose of Ad5-FGF4 met improvement standards for exercise time on a treadmill at four weeks and 45 percent improved at 12 weeks. The trial identified two doses to be advanced into a Phase IIb/III trial.
Collateral, of San Diego, said the trial also produced positive efficacy results for the therapy compared to placebo. Collateral plans to initiate a randomized, double-blind, placebo-controlled study to evaluate the two dose levels identified in the Phase I/II trial in a larger number of patients. The Phase IIb/III trial will evaluate prolongation in exercise duration on a treadmill, anginal frequency, quality of life, anti-anginal medication usage and long-term coronary events.
In other news from ACC:
¿ Alteon Inc., of Ramsey, N.J., said Phase IIa study results indicated that ALT-711 improved arterial elasticity and reduced pulse pressure. The thiazolium-based compound is an advanced glycosylation end-product crosslink breaker.
¿ Centocor Inc., of Malvern, Pa., said its clot-busting drug ReoPro showed positive effect in a study of 5,799 patients, reducing the risk of death three years after treatment when combined with an artery-opening procedure. The report presented an analysis of data from several clinical trials. Three years after treatment, the mortality rate of ReoPro-treated patients was 5 percent, compared with 6.3 percent for placebo.
¿ COR Therapeutics Inc., of South San Francisco, said results from a study of Integrilin combined with a half dose of TNKase in patients with ST-segment elevation myocardial infarction showed the therapy fully restored blood flow through blocked arteries, supplying oxygen-starved heart muscle in 70 percent of patients within an hour of initiation of therapy. The findings are based on results from the first phase of a Phase II study.
¿ CV Therapeutics Inc., of Palo Alto, Calif., said further analysis of its MARISA trial demonstrated that patients with chronic angina and a history of congestive heart failure tolerate ranolazine and respond to it as well as angina patients without congestive heart failure. At trough plasma concentrations ranolazine produced statistically significant (p<0.001) increases in exercise duration, time to angina and time to 1 mm ST segment depression compared to placebo in angina patients without congestive heart failure. Results from the Phase III MARISA (monotherapy assessment of ranolazine in stable angina) trial were presented initially at the 2000 Scientific Sessions of the American College of Cardiology.
¿ Interleukin Genetics Inc., of Waltham, Mass., said individuals with an interleukin-1 gene polymorphism are up to five times as likely to have had myocardial infarction before reaching 60 compared to individuals without the polymorphism. The study indicated that patients with a history of myocardial infarction before the age of 60 were five times more likely to have two copies of the polymorphism than patients without a history of myocardial infarction. About 8 percent of the Caucasian population has two copies of this IL-1 polymorphism.
¿ NitroMed Inc., of Bedford, Mass., said it initiated a study designed to confirm the efficacy of BiDil in treatment of African American heart failure patients, the first conducted exclusively in black men and women suffering from heart failure. The double-blind, placebo-controlled study is designed to confirm the safety and efficacy of BiDil, a combination drug containing isosorbide dinitrate and hydralazine hydrochloride. n