Neurochem (International) Limited (Neurochem), a wholly owned subsidiary of Neurochem Inc, headquartered in Québec, Canada, announced that it has submitted a complete response to the US FDA approvable letter for eprodisate (1,3-propanedisulfonate, Kiacta™, formerly Fibrillex™), an oral investigational product candidate for the treatment of amyloid A (AA) amyloidosis.
 
According to the company, the approvable letter from the FDA requested additional safety and efficacy data, as well as further manufacturing and pharmacokinetic information. The FDA stated that the efficacy information would probably need to be addressed by one or more additional clinical trials, but left open the possibility that significant findings obtained from a complete follow-up of patients in the ongoing eprodisate phase II/III open-label extension study could be sufficient. The FDA also stated that a "QT" clinical study should be submitted as part of a phase IV (postapproval) commitment. The complete response submitted by the Company includes the data on safety and efficacy from a follow-up of all 183 patients who were enrolled in the phase II/III clinical trial. Neurochem retrieved the most recent health information (ie, dialysis/end stage renal disease (ESRD) or death from all causes, regardless of when the clinical event occurred) for all 183 study subjects, including patients currently enrolled in the open-label extension study and all patients who discontinued participation in the study. The median time of follow-up was approximately 36 months.

The results of the follow-up analysis included in the complete response are the following: In the Kiacta group, fewer patients (18) progressed to dialysis/ESRD vs patients in the placebo group (32). The Kaplan-Meier plot and log-rank analysis showed that it took longer for the Kiacta group to progress to dialysis/ESRD than the placebo group (log-rank test; P-value of .018). The follow-up analysis on the composite endpoint of dialysis/ESRD or death was also in favor of the Kiacta group as fewer patients (32) progressed to dialysis/ESRD or death vs patients in the placebo group (44). The Kaplan-Meier plot and log-rank analysis showed that it also took longer for the Kiacta group to progress to dialysis/ESRD or death than the placebo group (log-rank test; P-value of .062). The follow-up analysis also showed that 56 patients progressed to death from all causes: 25 patients were from the group originally randomized to Kiacta and 31 patients were from the group originally randomized to placebo. The updated safety information shows that Kiacta continues to be safe and tolerated over long-term exposure in the two groups (originally randomized to Kiacta or placebo).

The phase II/III clinical trial for Kiacta was a 2-year, international, multicenter, randomized, double-blind, placebo-controlled, and parallel-designed trial to evaluate the efficacy and safety of Kiacta in patients suffering from AA amyloidosis confirmed by biopsy and renal involvement. The study, conducted at 27 sites located across North America, Europe, North Africa, and Israel, enrolled 183 patients and was completed in 2005. All patients who completed the trial were invited to join the ongoing open-label phase II/III extension study. Neurochem filed a New Drug Application (NDA) with the FDA for Kiacta for the treatment of AA amyloidosis in February 2006 and received the approvable letter in August 2006.

In September 2006, Neurochem announced that its Marketing Authorization Application (MAA) for Kiacta had been validated by the European Medicines Agency, confirming that the regulatory review had started. The Company is seeking marketing approval of Kiacta for the treatment of AA amyloidosis in the European Union (EU). The MAA for Kiacta will be reviewed under the Centralized Procedure, where marketing authorization is applied for all EU member states (numbering 25 countries today), plus Norway and Iceland.
 
AA amyloidosis is a progressive and fatal condition that occurs in a proportion of patients with chronic inflammatory disorders including rheumatoid arthritis and Crohn's disease, and chronic infections and inherited diseases, such as familial Mediterranean fever. The kidney is the organ most frequently affected by AA amyloidosis, and progression to dialysis/ESRD is the most common cause of death.  Patients suffering from AA amyloidosis have a poor prognosis with 5- to 15-year survival rates of 50% and 25%, respectively. 

Neurochem has granted Centocor, Inc, a wholly owned subsidiary of Johnson & Johnson, exclusive distribution rights for Kiacta worldwide, with the exception of Canada, Switzerland, Japan, China, South Korea, and Taiwan.

—A. Techman

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