A Cardiovascular Device Update

Scios (Sunnyvale, California) presented pivotal Phase III trial results from its lead product, Natrecor, at the 73rd scientific sessions of the American Heart Association in New Orleans, and said it planned to file an amended new drug application (NDA) by the end of the year. "We met all of our endpoints and we beat what is currently the standard of care," said Richard Brewer, president and CEO of Scios. "It's hard to get better than that."

Results from the Vasodilation in the Management of Acute Congestive (VMAC) heart failure study showed that Natrecor, a recombinant form of B-type natriuretic peptide, improved both the hemodynamic measures associated with acute decompensated congestive heart failure and alleviated dyspnea, or difficulty breathing.

Scios had its original NDA returned in 1999 when the FDA denied Natrecor's approval, pointing to hypotension reports in some patients as the reason. The new data address the FDA's concerns, Brewer said. "We believe we have answered everything," he said. "We will be filing the amended NDA by the end of this year. [The FDA] has six months to respond, so a response could come by the middle of next year."

The primary analysis compared the effects of Natrecor and placebo at three hours. Primary endpoints were change in pulmonary capillary wedge pressure (PCWP) and a clinical evaluation of the patient's dyspnea. Natrecor had a statistically significant effect on the primary endpoint, reducing PCWP in as little as 15 minutes and sustaining it for at least 48 hours without any loss of effectiveness. At three hours, patients treated with Natrecor had significant improvement in PCWP, compared to those patients given placebo and those patients given IV nitroglycerin.

Assuming approval, "It positions us as the new standard of care for this particular disease," Brewer said. "The results, coupled with our pipeline, make us a very different kind of company."

In other news from the AHA sessions:

Ariad Pharmaceuticals (Cambridge, Massachusetts) said its Argent cell-growth, switch-engineered muscle cells may be used for heart transplantation as a potential treatment for heart muscle damage due to myocardial infarction or cardiomyopathy. Treatment of engineered myoblasts incorporating the cell-growth switch using Argent's small-molecule Dimerizer drug resulted in selective proliferation without deleterious effects on other cardiac cells, according to a study presented by Ariad collaborators from the University of Washington (Seattle, Washington).

CV Therapeutics (Palo Alto, California) presented data from several studies. A subgroup analysis of a Phase III chronic angina trial for ranolazine, taken as monotherapy, showed it produced statistically significant increases in exercise duration and time to angina pain compared to placebo in both younger and older patients with chronic angina. Ranolazine is an investigational candidate in a new class of anti-anginal drugs called pFOX – partial Fatty Acid Oxidation – inhibitors. In a preclinical trial on ranolazine, results suggested it might increase the efficiency of the pumping action of the heart in dogs with experimentally induced congestive heart failure. Results from a Phase II clinical trial for CVT-510 indicated it terminated paroxysmal supraventricular tachycardia without adversely affecting blood pressure. The trial was designed to test CVT-510 in patients suffering from PSVT, a type of atrial arrhythmia that involves the AV node. In 32 of 37 patients, PSVT was terminated and normal rhythm was restored. A second Phase II trial is being conducted in patients with atrial fibrillation. And results of an in vitro study demonstrated certain compounds can turn on production of the ABC1 protein that pumps excess cholesterol out of cells, which in turn should raise high density lipoprotein levels.

Fibrogen (South San Francisco, California) gave a presentation titled "Inhibition of Myocardial Fibrosis Improves Survival and Prevents Progression of Heart Failure After Myocardial Infarction." Researchers treated both a rat model of coronary artery occlusion and randomized animals with Fibrogen's proprietary P4H inhibitor or placebo. After four weeks of treatment, both collagen deposition and mortality were significantly reduced in the P4H treatment arm.

A new venture, First Nuclear, will provide a sort of "plug-and-play" turnkey set-up for clinics wishing to offer full nuclear imaging services, with no start-up costs. The venture will combine the diagnostic hardware of ADAC Laboratories (Milpitas, California) with the imaging pharmaceuticals supplies and expertise of Cardiolite (North Billerica, Massachusetts), and the management and administrative services of American Diagnostic Medicine (Elmhurst, Illinois). First Nuclear combines companies with "the biggest market share in each of their sectors; all you have to do is supply a 14-by-14 room," an American Diagnostic Medicine representative told CDU.

GE Medical Systems (Waukesha, Wisconsin) and CardioDynamics International (San Diego, California) previewed their BioZ ICG module. The companies are jointly developing the module to integrate CardioDynamics' BioZ technology into GE Medical's Solar patient monitoring systems. Both companies were displaying the BioZ module in order to solicit investigators to complete its clinical testing. In addition, GE Medical rolled out Tissue Tracking, an adjunct to cardiovascular ultrasound for tracking the systolic movement of the heart wall; SmartScore Pro, a new cardiac analysis software which is combined with the company's LightSpeed multi-slice CT scanner, for integrating a variety of scoring information; and the GE 30-Minute Comprehensive Cardiac MRI Exam, a combination of GE features in a systems approach for obtaining "relevant images" of a patient's heart and coronary arteries much more quickly than standard MRI or invasive imaging procedures.

Idun Pharmaceuticals (La Jolla, California) said scientists from the Albert Einstein College of Medicine (New York) presented two papers with evidence suggesting caspase inhibitors may have therapeutic potential for the treatment of chronic heart disease. Idun and the college are collaborating in this area.

PLC Systems (Franklin, Massachusetts), a pioneer in the field of transmyocardial revascularization, spotlighted five-year clinical evidence that the effects of laser treatment are long-lasting. Presented by Keith Horvath, MD, of Northwestern University Medical Center (Chicago, Illinois), the study uses standard heart disease classifications and reported 68% of patients "had successful long-term angina relief."

St. Jude Medical's Cardiac Rhythm Management Division (Sylmar, California) was showing its just-unveiled Photon DR dual-chamber implantable cardioverter defibrillator. While St. Jude is the last of the sector titans to develop a dual-chamber ICD product, the company obviously hopes, with the latest in diagnostic and patient management features, that the Photon will give it rapid catch-up in this arena.

A unique technology in the "looking for partners" category was SQUID (for Superconducting QUantum Interference Device). This cardiac diagnostic system was represented by two firms on the exhibit floor: SQUID (Essen, Germany) and CardioMag Imaging (CMI; Schenectady, New York), which calls its SQUID technology Magnetocardiography (MCG). While the SQUID system uses superconducting magnetic sensors, the technology is not a version of magnetic resonance imaging. Rather than sending electromagnetic frequencies through the body, the system only senses the body's own natural electromagnetic activity and, specifically, is used for mapping anomalies in the heart such as impaired coronary flow, according to a statement by CMI. The strategy is to use extremely low impact sensors, cooled in a cryostat with liquid helium, which can detect the weak magnetic signals of the heart while screening out artifact noise. CMI said it is preparing the ground for FDA clearance. Representatives of the German firm have yet to begin that process in America, saying that they were attending the AHA gathering primarily as a fishing excursion to find U.S. partners.