Neurochem Inc.'s international subsidiary began submitting a rolling new drug application for Fibrillex, its investigational product for amyloid A (AA) amyloidosis, despite a clinical study misstep reported earlier this year.
In fact, those regulatory plans have been discussed openly for several months, and the filing has begun earlier than first expected. Neurochem (International) Ltd., Neurochem's wholly owned business in Ecublens, Switzerland, plans to complete its submission around the end of the year. A decision could come as early as the middle of next year.
"We will work closely with the FDA," Lise Hebert, Neurochem's vice president of corporate communications, told BioWorld Today, "and move from one step to the next to make this product available."
The oral compound, which works by preventing amyloid fibril formation, has been designated an orphan drug in the U.S. and Europe, as no specific treatment exists for AA amyloidosis, a progressive and fatal condition that occurs in certain patients with chronic inflammatory diseases and presents as renal dysfunction. A member of the glycosaminoglycan (GAG) mimetic class of drugs, it also has fast-track designation in the U.S. and has been accepted into the Pilot 1 and 2 programs by the FDA's Division of Cardio-Renal Drug Products.
"Right now, patients cannot treat the fibrils that slowly cause the problem in their various organs," Hebert said, "the most important ones being their kidneys."
Earlier this summer, the FDA gave the Laval, Quebec-based company a green light to proceed with the filing despite missing a Phase II/III trial's primary endpoint. Still, findings from that study demonstrated positive trends in AA amyloidosis patients, and the agency encouraged Neurochem to look at and provide additional follow-up data collected from the open-label extension study as part of its submission. The company continues to collect data on all parameters observed in the study's randomized phase. (See BioWorld Today, April 19, 2005.)
"We met with the FDA in June and presented the data that we had," Hebert said, "and then submitted a request to file the NDA, to which they agreed."
The 183-patient study randomized 89 to a Fibrillex arm and 94 others to placebo, and after a 24-month treatment period, 13.4 percent more Fibrillex patients exhibited stabilized or improved kidney function (p=0.06). To have met the primary endpoint, there should have been 20 percent more stabilized or improved patients in the Fibrillex group vs. placebo (p=0.01).
"However, when you look into the data, it appears that Fibrillex helps with the decline in kidney functions," Hebert said. "We had less patients worsening on the Fibrillex arm, and up to now, it has shown a benign safety profile."
The company, which shares an exclusive collaboration and distribution agreement for Fibrillex with Centocor Inc., of Malvern, Pa., estimates there to be more than 40,000 patients in North America and Europe. Neurochem, which is responsible for the drug's regulatory filings, is due undisclosed compensation from Centocor for the NDA. Should it receive approval, Centocor, a Johnson & Johnson company, would handle sales. Hebert declined to discuss the partners' profit-sharing arrangement.
In Europe, discussions are under way on a regulatory pathway for Fibrillex. Should the product receive licensure there, Centocor would handle the distribution side of the equation.
Beyond that drug, Hebert noted that Neurochem has completed enrollment in its North American Phase III trial of Alzhemed to treat Alzheimer's disease. The product, which is designed to inhibit both the deposition of cerebrovascular amyloid beta and its plasma concentration, soon will enter Phase III in Europe as well.
On Monday, Neurochem's stock (NASDAQ:NRMX) gained 8 cents to close at $11.04.