Regulatory Decision Summary for Ferriprox, Ferriprox MR

This Supplement to a New Drug Submission (SNDS) for Ferriprox, Ferriprox MR was filed by Chiesi Canada Corp., to seek the approval of a new dosage form (modified-release tablets, Ferriprox MR) for the 1,000 mg strength of the product. This would allow for twice daily dosing with the MR formulation, as opposed to three times a day with the immediate-release (IR) formulation. In addition, Chiesi Canada Corp., had updated the Product Monograph (PM) format for Ferriprox, Ferriprox MR to align with the 2020 Health Canada Master Template.

The sponsor conducted two pivotal comparative bioavailability studies to support the submission seeking approval for a new Ferriprox MR modified-release 1,000 mg tablets: LA53-0116 and LA45-0116. The studies compared the proposed tablet to the currently approved Ferriprox immediate-release 500 mg tablet, compared the proposed tablet when administered under fasting and fed conditions, and compared the intact Ferriprox MR tablet to ones that were split prior to administration, under fed conditions. Results of study LA53-0116 demonstrated that the extent of exposure to a single 1,000 mg dose of Ferriprox MR tablet formulation is equivalent to a single 1,000 mg dose of Ferriprox immediate release tablet formulation under fed condition. Results also showed that food does not impact the pharmacokinetics of intact modified-release tablets and that administration of intact Ferriprox MR 1,000 mg tablets and those split into two halves have comparable bioavailability of deferiprone under fed conditions. While there was a slight increase in peak plasma concentration with the split tablets, this was not considered a significant concern, since it usually constitutes only a fraction of the total dose administered. Results of study LA45-0116 demonstrated that the peak and extent of exposure to 1,500 mg Ferriprox MR modified-release tablets (1.5 x 1,000 mg tablets) taken twice daily is equivalent to that of 1,000 mg Ferriprox (2 x 500 mg tablets) taken three times daily over 24 hours at steady state under fed conditions. Since the comparative bioavailability study was conducted under fed conditions, it is recommended in the product monograph that Ferriprox MR should be taken with food.

The overall safety profile of Ferriprox MR modified-release 1,000 mg tablet was evaluated in 3 multiple-dose studies, two in healthy volunteers (LA58-0117 and LA60-0118) and one in patients with iron overload (LA61-0218). In the two multi-dose safety and tolerability studies conducted in healthy volunteers, although no serious safety issues were seen, two types of adverse events of concern were noted: gastrointestinal distress (specifically, nausea and vomiting) and elevations of liver enzymes. In study LA61-0218, Ferriprox MR was administered to patients with iron overload without any serious safety concerns. Overall, the safety profile of Ferriprox MR was consistent with the safety profile of Ferriprox. Agranulocytosis is an important identified risk with deferiprone, however no evidence of agranulocytosis was observed in subjects treated with Ferriprox MR. The observed risks are generally manageable with dose discontinuation and/or standard medical practice. Current labelling and risk mitigation measures are adequate at this time.

This submission was considered to comply with the Quality data requirements of Section C.08.002 of the Food and Drug Regulations.

The labelling documents conform to the necessary regulatory requirements and are consistent with the labelling guidance documents.

The Risk Management Plan was considered acceptable. The potential risk of medication errors due to the potential switch between formulations was properly addressed by having an MR modifier to the brand name, packaging blisters to differentiate from other formulations, textbox banner on the carton, bottle reminder tag, PM and PMI labeling and a reminder card and patient brochure with their first three shipments.

In conclusion, the clinical data supports that Ferriprox MR 1,000 mg is effective and safe for the target population. The safety profile of Ferriprox MR is considered acceptable in the target population of patients with iron overload. Key clinical findings, relevant risks, and uncertainties were properly addressed in the final product monograph. The overall benefit-harm-uncertainty profile is considered positive for Ferriprox MR 1,000 mg formulation.