By Lisa Seachrist

Washington Editor

BETHESDA, Md. -- An FDA advisory panel voted 9-to-1 to recommend that the agency approve Neurex Inc.'s antihypertensive, Corlopam, for the treatment of severe high blood pressure.

With one dissenter, the Cardiovascular and Renal Drugs Advisory Committee decided the Menlo Park, Calif., company had shown that intravenous Corlopam (fenoldopam) effectively lowered blood pressure in patients who couldn't use oral therapy and in patients with critically high blood pressure.

"We are very pleased to get the recommendation for approval," said Robert Luther, senior vice president of development at Neurex.

The panel, however, also recommended that the company conduct further study of the drug in combination with beta blockers -- a set of compounds that could potentially accelerate Corlopam's blood pressure-lowering effects. The panel split 5-to-5 over whether the study should take place before or after Corlopam is approved for marketing.

"The beta blocker issue was not one of the issues that we expected to hear today," Luther told BioWorld Today. "We will have to wait to hear from the agency and review existing data before answering the question, but I don't expect is will affect approval."

Corlopam is a highly specific and potent dopamine receptor agonist that causes dilation of blood vessels throughout the body. In addition, the drug specifically acts on the kidneys to increase blood flow. As such, Corlopam not only controls blood pressure, but also protects the kidneys, which can be damaged by both high and low blood pressure.

Corlopam was originally discovered by SmithKline French as an oral treatment for hypertension. However, the company had problems formulating it into a bioavailable agent. In 1988, SmithKline Beecham plc filed a new drug application with the FDA for intravenous use of Corlopam. That effort received a nonapprovable letter in 1991 because an appropriate dosing schedule had not been established.

In 1994, Neurex licensed the drug from SmithKline Beecham plc and started targeted clinical trials to establish a dosing regimen as well as efficacy in "malignant hypertension" -- severely high blood pressure that threatens to damage the heart, kidneys and other organs.

The company presented data showing that Corlopam successfully lowered patient's blood pressure on average by 30 points within four minutes after administration. The drug, with a half-life of five minutes, rapidly starts to lower blood pressure and is quickly cleared from the system when the infusion stops.

In addition, side effects were relatively benign: nausea, flushing, headache and hypotension. And,there were no drug-associated deaths in the clinical trials.

However, one common effect of higher doses of Corlopam was increased heart rate, which some panel members noted could indicate that the heart isn't getting enough oxygen.

Marvin Konstam, professor of medicine at the New England Medical Center, in Boston, noted that doctors may want to prescribe beta blockers concomitantly in order to slow the heart down. Konstam wanted to know whether these drugs accelerated Corlopam's effect.

"My suspicion is that this drug will be used with beta blockers," Konstam said. "I would like to know what this does to the dose response."

Konstam went on to say that he felt that Corlopam was an approvable drug, but was worried that if the agency put a warning on the label that beta blockers shouldn't be used with Corlopam, it would "handcuff the drug."

The entire panel agreed that it wanted to see more information, but five wanted the company to investigate before the agency approved the drug and five felt the answers could be determined after the drug was on the market.

However, the panel in the end voted that Corlopam showed an antihypertensive effect and that the company had provided adequate dosing information. Lemuel Moye, an associate professor of biometry at the University of Texas Health Science Center, in Houston, disagreed, noting that it was "uncomfortable with the way the dose response was determined and uncomfortable with the size of the database." Neurex presented a database of 1,267 patients who had been exposed to intravenous Corlopam.

Franklin Berger, an analyst with Josephthal Lyon & Ross said that the panel's decision was a very important positive step for Neurex.

"This shows that they have the clinical and regulatory capabilities to bring a drug through the approval process," Berger said. "And it gives them the potential for revenue as they develop their core product for pain, SNX-111."

Neurex's stock (NASDAQ:NXCO) was up $1.50 to $17.125 on the news.

Luther noted that the company also is trying to develop oral or transdermal formulations of Corlopam for chronic treatment of hypertension. *