While Fibrillex demonstrated a positive trend in AA amyloidosis patients, a Phase II/III trial missed its primary endpoint, causing Neurochem Inc.'s stock plunge of 28.5 percent.

The Laval, Quebec-based company watched its shares (NASDAQ:NRMX) fall $3.15 Monday to close at $7.92.

Despite the missed endpoint, Neurochem intends to forge ahead with plans to file a new drug application. The original plan was to file it this year, following the results.

Lise Hébert, Neurochem's vice president of corporate communications, said it is premature to say whether the filing will be delayed. It could remain on track, considering Fibrillex showed an improvement over placebo for an orphan indication that currently has no specific treatment.

"The next step is to finalize the analysis of the data, gather the information and meet with the FDA to present the information," Hébert said. "That's going to be the key right now and the core of our strategy with Fibrillex."

The trial enrolled 183 patients, of which 89 were randomized to receive Fibrillex and the other 94 received placebo. Over a 24-month treatment period, researchers sought to determine the ability of Fibrillex to treat the disease and to assess safety in patients with impaired renal function at baseline. In order to meet the primary endpoint, which looked at kidney function measurements and death, there had to be 20 percent more stabilized or improved patients in the Fibrillex-treated group compared to placebo (p=0.01). Instead, there were 13.4 percent more Fibrillex-treated patients that reached the endpoint (p=0.06).

The preliminary results of the trial were announced by Neurochem's wholly owned subsidiary, Neurochem Ltd., of Ecublens, Switzerland.

"The trial now is going to teach us a lot of information, as this is the largest placebo-controlled trial that has been done with this disease," Hébert said. "And it will help us, hopefully, to move forward."

Fibrillex displayed a clinical effect on the course of the disease, when measured by its secondary efficacy endpoints: the decline in renal function, including progression to end-stage renal failure and dialysis, and the slope of decline of creatinine clearance. The drug was well tolerated and showed similar adverse events as placebo.

The data will be presented at international medical conferences this quarter. Fibrillex is part of the FDA's Continuous Marketing Applications Pilot 2 program designed to accelerate the development and marketing of certain product candidates. The Cardio-Renal Drug Product Division selected Fibrillex for the program. Neurochem intends to continue to supply Fibrillex to patients receiving the drug through the 24-month ongoing open-label extension study.

"At the present time, there are no specific treatments to treat AA amyloidosis," Hébert said.

Neurochem had just completed the treatment portion of the Phase II/III trial in December when it signed a $54 million partnership with Centocor Inc., of Malvern, Pa. Centocor gained exclusive distribution rights, covering all markets except Canada, Switzerland, China, Japan, Taiwan and South Korea. Neurochem remained responsible for U.S. and European Union product approvals and global manufacturing activities. (See BioWorld Today, Dec. 23, 2004.)

Neurochem expects to seek an Asian partner, but plans to market Fibrillex on its own in Canada and Switzerland. As of Monday, Centocor appeared to be standing by the product.

"We have not heard anything that would make us suppose that it changes anything to the Centocor deal," Hébert said.

AA amyloidosis, which affects about 270,000 people worldwide, normally progresses to end-stage renal failure and death. From disease onset, about half of patients die within five years. It occurs in certain patients with chronic inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis and Crohn's disease, and in patients with chronic infections or inherited inflammatory diseases, such as familial Mediterranean fever. Symptoms are renal dysfunction and gastrointestinal problems like chronic diarrhea, bleeding, abdominal pain and malabsorption. Some patients experience enlargement of the liver and the spleen.

Fibrillex (1,3-propanedisulfonate) has orphan drug status in both the U.S. and Europe. The product is designed to prevent amyloid fibril formation.

Aside from Fibrillex, Neurochem is developing Alzhemed (3-amino-1-propanesulfonic acid) to treat Alzheimer's disease in a Phase III trial, and Cerebril (3APS) to prevent hemorrhagic stroke caused by cerebral amyloid angiopathy, which has completed a Phase IIa trial. A second Phase III trial of Alzhemed is scheduled to begin in Europe during the second half of this year, while a Phase IIb trial of Cerebril is slated to start at the end of the year.

Neurochem raised $61.2 million in a public offering last month to fund the Phase III trials of Alzhemed. (See BioWorld Today, March 7, 2005.)