Neurochem (International) Ltd (ECUBLENS, Switzerland), a wholly-owned subsidiary of Neurochem Inc, announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a negative opinion recommending refusal of the marketing authorization application for eprodisate (Kiactaâ„¢) for the treatment of Amyloid A (AA) amyloidosis. Neurochem is currently reviewing all of its options in view of this opinion, including requesting a reexamination of the opinion by CHMP.

The effectiveness of eprodisate was studied in one main study involving 183 patients with AA amyloidosis, in which eprodisate was compared with placebo. The main measure of effectiveness was the number of patients whose kidney function got significantly worse or who died over 2 years of treatment. CHMP was concerned that the effectiveness of eprodisate in treating AA amyloidosis had not been demonstrated sufficiently in the study. Although there was a suggestion that eprodisate may be active, the committee concluded that another study would be needed to demonstrate the medicine's effectiveness. In addition, following an inspection of the site where the data from the study were analyzed, CHMP had concerns over the reliability of the study's findings because of the way the analysis was carried out.

In the US, the FDA has acknowledgement complete response from Neurochem to the second approvable letter of July 2007 for the New Drug Application (NDA) for eprodisate for the treatment of AA amyloidosis, allowing for the Class 2 review. The Prescription Drug User Fee Act goal date by which the FDA is expected to render a decision is April 2, 2008. The NDA for approval of eprodisate was filed in February 2006.

Eprodisate was investigated in an international, randomized, double-blind, placebo-controlled, and parallel-designed phase II/III clinical trial in which 183 AA amyloidosis patients were enrolled at 27 sites. Patients who completed the clinical trial were eligible for enrollment in an ongoing open-label extension study, some of whom have now been receiving eprodisate for more than 6 years. Eprodisate has received orphan drug status in the US, the EU, and in Switzerland.

Neurochem also filed for marketing approval for eprodisate for the treatment of AA amyloidosis in Switzerland, where a decision is expected in 2008.

AA amyloidosis occurs in a proportion of patients with chronic inflammatory disorders, chronic infections, and inherited diseases such as familial Mediterranean fever; it is a progressive and fatal condition. The kidney is the organ most frequently affected and progression to dialysis/endstage renal disease is the most common clinical manifestation in this disease. Currently, there is no approved therapy to treat AA amyloidosis and about half of all patients diagnosed with the disease die within 5 years of diagnosis.