By Brady Huggett
Scios Inc. presented pivotal Phase III trial results from its lead product, Natrecor, at the 73rd Scientific Sessions of the American Heart Association in New Orleans Wednesday, and said it planned to file an amended new drug application 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, of Sunnyvale, Calif., had its original new drug application (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. (See BioWorld Today, April 29, 1999.)
"We believe we have answered everything," Brewer 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. Other endpoints compared the hemodynamic and clinical effects of Natrecor with IV nitroglycerin at longer observation periods.
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. Patients also had improved breathing, compared to placebo.
The most common adverse side effect reported was headache.
"It was really a win across the board," Brewer said. "I think it positions us, assuming approval, as the new standard of care for this particular disease."
In 1999, when Scios first handed the FDA its NDA, the company suggested it would reach profitability by the year 2000. The results from this trial allowed Brewer to adjust that schedule.
"I would say 2003, although it could occur sooner than that," Brewer said. "We will have to spend money on building our own sales force and marketing costs can be pretty high, but we are saying 2003."
Regardless, the positive data are good news.
"We are delighted with the results," he said. "The results, coupled with our pipeline, make us a very different kind of company."
Scios' stock (NASDAQ:SCIO) moved up $1.062, or about 7 percent, on the news Wednesday, to close at $16.062.
In other news from the AHA sessions:
¿ CV Therapeutics Inc., of Palo Alto, Calif., 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 (p<0.001) 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 Inc., of South San Francisco, 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.
¿ Idun Pharmaceuticals Inc., of La Jolla, Calif., said scientists from the Albert Einstein College of Medicine in 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.