By Lisa Seachrist
WASHINGTON — Interneuron Pharmaceuticals Inc. began a new Phase III trial of its stroke drug, CerAxon (citicoline sodium), making good on a promise to move forward with the drug following a Phase III trial failure in April.
This time, the firm will seek to enroll 900 patients in order to test the drug's ability to improve neurological function in patients suffering from moderate to severe ischemic stroke. The Lexington, Mass.-based company also has decided to increase the dosage given to participants in this new study compared with that given in the previous study.
"By increasing the dosage and expanding the size of the trial, we think we will address any placebo response anomalies typically seen in clinical trials," said William Boni, vice president of corporate communications for Interneuron.
Reports in April that the Phase III study of CerAxon had failed to reach either its primary or secondary endpoint sent the company's stock plummeting 47 percent. In addition, Interneuron was forced to withdraw the new drug application (NDA) it had filed in December. (See BioWorld Today, April 21, 1998, p. 1.)
That study included approximately 100 patients and tested whether 500 milligrams of the drug could reduce the infarct size compared with placebo. The secondary measure was whether CerAxon could offer improved neurological function.
While many neurologists believe that controlling the infarct size is vital to preserving neurological function following a stroke and view it as a surrogate marker for outcome, Boni noted the FDA has not approved a reduction in infarct size as a surrogate marker.
In fact, it was only last year the FDA approved a technique called diffusion weighted magnetic resonance imaging as a means for measuring the amount of necrotic tissue caused by lack of blood flow — infarct — in the brain.
"In stroke, the gold standard for a drug is improved neurological function," Boni said. "And that is what we are using as the primary endpoint of this study."
Taking into consideration the results of a dose-ranging study showing a CerAxon dose of 2,000 milligrams per day was safe and effective, the company is upping the dosage used in the new trial.
The newly initiated study will be conducted at more than 90 clinical sites and will compare the neurological function of treated patients with placebo patients 12 weeks following stroke. Patients will take either 2,000 milligrams of CerAxon daily or placebo daily for six weeks following the stroke.
The company expects the trial to be completed in the second half of 1999.
"We remain very positive about CerAxon and the reason is that the drug has a 24-hour window of opportunity and it's an oral formulation, which is convenient for many patients," Boni said. "The thrombolytics are for acute therapy, but neuroprotectives like CerAxon have both acute and long-term restorative effects."
Citicoline, which is produced by Ferrer Internacional SA, of Barcelona, is approved for treatment of stroke and age-related memory loss and motor skills loss in more than 20 countries. The drug works by stimulating the production of membrane in damaged nerve cells, which helps the cells survive.
Interneuron licensed the U.S. and Canadian rights to the drug from Ferrer. Interneuron has received a notice of allowance from the U.S. Patent and Trademark Office for a patent based on the company's findings in animal and clinical studies showing the protection of brain tissue form cerebral infarct.
As a result of expanding the patent estate of the drug, Interneuron signed an agreement with Ferrer for the use of Interneuron's patent rights relating to the use of citicoline in the protection of brain tissue after ischemic stroke. The agreement would grant Interneuron royalties from the sales of CerAxon in countries outside the U.S. and Canada.
Interneuron's stock (NASDAQ:IPIC) closed Tuesday at $4.156, up $0.281. *