By Randall Osborne
With an unfavorable analysis of preliminary data from the most recent Phase III trial of CerAxon (citicoline sodium) for ischemic stroke, Interneuron Pharmaceuticals Inc. withdrew its new drug application (NDA) from the FDA and vowed yet another trial.
"It's a bad break, but we're moving forward and the drug is very alive," said William Boni, spokesman for Lexington, Mass.-based Interneuron.
The company's stock (NASDAQ:IPIC) plummeted on the news, ending Monday at $7.937, down 47 percent from Friday's close of $15.062.
CerAxon failed to meet its primary and principal secondary endpoints. In the first, no difference was detected in reduction of infarct size among patients with ischemic stroke who received 500 milligrams per day of the drug, compared with those who received placebo.
In the second, no improvement was shown in treated patients as compared with those in the placebo group.
"The placebo group experienced infarct size reduction nearly twice what the literature would suggest," Boni told BioWorld Today.
In July, a preliminary analysis of data from the second Phase III trial showed improved neurological function for moderate to severe stroke patients, but no significant benefit over placebo for those with mild stroke. (See BioWorld Today, July 17, 1997, p. 1.)
"We were looking [in the most recent Phase III study] for results that would overcome any statistical difficulties in that earlier trial," Boni said. "But this trial only compounded the situation."
Just last year, the FDA approved a technique for measuring size of an infarct, or area of necrotic tissue caused by lack of blood flow. The technique is diffusion weighted magnetic resonance imaging.
"This was the first significant trial in stroke drug development that has looked at infarct size reduction and tried to correlate it with neurological function," Boni said.
The failure of the drug in this trial "makes it hard for investors, especially those who saw us through the Redux situation," he added.
Interneuron and Wyeth-Ayerst Laboratories, a division of American Home Products, of Madison, N.J., withdrew their diet drug Redux (dexfenfluramine hydrochloride) from the market last fall because of news associating it with heart valve difficulties. (See BioWorld Today, Sept. 16, 1997, p. 1.)
The NDA for CerAxon was submitted late last year. A new, 700-patient trial for the drug will begin "in another couple of months," Boni said, with results expected by the end of 1999.
"What makes this particularly frustrating is that there's ample evidence from previous trials that the drug provides benefit," he said.
"We had hoped to get a review and approval by the middle of this year, June or so," Boni said. "But the gods of clinical trials play funny tricks sometimes. There's no logical explanation for it." *