Regulatory Decision Summary for MDK-NITISINONE

This submission was based on demonstration of bioequivalence of MDK-Nitisinone to Orfadin, allowing bridging between the MDK-Nitisinone formulation and the product used in literature-based studies and providing evidence of the safety and efficacy of MDK-Nitisinone. This was combined with evidence of the safety and efficacy of Orfadin from marketing authorization reviews of other regulators, literature studies and post-market safety data.

Uncertainties included the effects of advanced age, chronic treatment, renal impairment, hepatic impairment, race, and genetic polymorphisms on the pharmacokinetics of nitisinone and safety when used during pregnancy and lactation.

A Risk Management Plan was deemed acceptable by the Marketed Health Products Directorate. Risk minimization includes ongoing post-marketing surveillance, creation of a Pan-Canadian Patient Registry to evaluate the long-term safety and adequate labelling of all identified safety issues, including the lack of data in some subpopulations, and the potential risk from use during pregnancy and lactation, along with the potential for risk to the fetus and mother from discontinuing nitisinone during pregnancy.

The evidence of the benefit provided by nitisinone for the treatment of hereditary tyrosinemia type 1, a serious and often fatal disorder for which no approved treatment exists in Canada, outweighs the associated risks.