By Kim Coghill

Washington Editor

BETHESDA, Md. ¿ In a unanimous vote, the Cardiovascular and Renal Drugs Advisory Committee on Friday recommended approval of Scios Inc.¿s Natrecor (nesiritide) for treating acute congestive heart failure.

Now is it is up to the FDA to decide whether Natrecor, an intravenous therapy used in hospitals, will enter the market as the first new treatment for acute congestive heart failure (CHF) in 12 years.

¿I¿m very pleased with the decision,¿ said Richard Brewer, president and CEO of Sunnyvale, Calif.-based Scios. ¿It has been a grueling day, but I think the committee did a good job going over the material.¿

The 10-0 recommendation is not binding on the FDA¿s decision, which is expected in July, though the FDA usually follows the recommendation of its advisory committees. With the FDA¿s go-ahead, Scios likely will launch in the third quarter.

Scios filed to take the drug into the clinic eight years ago. It filed the initial NDA in 1998, and in 1999 an advisory committee voted 5-3 recommending approval. But when the Natrecor application ended up in the hands of FDA officials, concerns surrounding safety and dosing prevented the drug from entering the market. (See BioWorld Today, Feb. 1, 1999, and April 29, 1999.)

Trading on Scios¿ stock (NASDAQ:SCIO) was held Friday. It had closed Thursday at $24.56.

The committee¿s ruling Friday is based on amendments to the existing NDA. The additional trials conducted after the 1999 failure were designed to satisfy the FDA¿s questions concerning hypotension as an adverse event. Other side effects associated with the product are dizziness or headaches.

Milton Packer, committee chairman and chief of the division of circulatory physiology at the Columbia University College of Physicians and Surgeons in New York, cautioned that ¿the vote we take at the end of these meetings, although it seems to generate an enormous amount of public interest, is just a small part of the process.¿

Natrecor is a parenteral formulation of nesiritide (a 32-amino acid peptide, produced by recombinant DNA technology) that is identical to B-type natriuretic peptide produced by the human ventricle.

The original NDA contained data from randomized studies enrolling 721 patients, including 505 patients who received nesiritide in a range of infusion doses between 0.003 and 0.025 microgram/kg/min.

The new recommended dose is about 30 percent lower than previously requested by the company.

¿We wanted to lower the dose to reduce hypotension, but we didn¿t want to lower it so much that it would be ineffective,¿ Darlene Horton, Scios¿ vice president of medical affairs, told the committee.

Committee member Steven Nissen, vice chairman of the Department of Cardiology and professor of medicine at Ohio State University, the Cleveland Clinic Foundation, asked whether Scios could assure him that Natrecor will be safe once it gets out in the community.

Horton responded that the 4 percent of patients who developed hypotension in the trials did not have to be taken off the product.

In the first of the new studies, called the Vasodilation in the Management of Acute Congestive, 489 patients with exacerbations of CHF and dyspnea at rest were randomized to placebo (142), nitroglycerin (143) or nesiritide (204) during a nine-month period. The primary endpoints (change in pulmonary capillary wedge pressure and patient self-evaluation of dyspnea) compared nesiritide to placebo at three hours. The participants were followed up for six months.

And the company conducted a third study, the Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Nesiritide Therapy (PRECEDENT).

In the PRECEDENT trial, Natrecor produced fewer arrhythmias (irregular heartbeats) and improved overall mortality rates compared to dobutamine, a commonly administered inotropic agent.

Analysts estimate the market for Natrecor to range between $200 million and $300 million at its peak. And in its first year, Natrecor should generate between $11 million and $12 million in sales. (See BioWorld Today, May 25, 2001.)

Scios in January signed a commercialization deal with Quintiles Transnational Corp., of Research Triangle Park, N.C., whereby Quintiles will fund the $35 million commercialization cost through its corporate group, PharmaBio Development.

Scios will receive $10 million of that funding within the first six months of Natrecor¿s launch. (See BioWorld Today, Jan. 12, 2001.)

Quintiles subsidiary Innovex Inc. will provide a 180-person sales force dedicated exclusively to Natrecor, for which Quintiles expects about a $100 million consideration through a net sales royalty stream over the 3.5-year agreement.

Also in January, Scios put 6.4 million shares on the shelf, filing to raise up to $120 million. The shares remain on the shelf. The company on March 31 reported having about 39.3 million shares outstanding. (See BioWorld Today, Jan. 22, 2001.)

Scios focuses on heart failure and inflammatory diseases. It has products in various stages of development for indications including Type II diabetes, coronary artery disease, rheumatoid arthritis and Alzheimer¿s disease. It licensed its recombinant form of basic fibroblast growth factor, called Fiblast, to Chiron Corp., of Emeryville, Calif., in a $24.5 million agreement. (See BioWorld Today, Nov. 3, 1999.)