Nitisinone (Nitisinone Tablets) is indicated for the treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. Nitisinone Tablets are available in 2 mg, 5 mg, and 10 mg strengths. The submitted price of nitisinone is based on dose: 2 mg ($12.95), 5 mg ($25.06), and 10 mg ($47.40). The recommended initial dose is 1 mg/kg body weight daily divided into two doses, administered orally. Patients whose plasma and urine succinylacetone are still detectable one month after starting treatment should be increased to 1.5 mg/kg/day, with a maximum of 2 mg/kg/day, based on the evaluation of all clinical parameters. If biochemical response is satisfactory, dosage should only be adjusted according to body weight.

The CADTH Common Drug Review (CDR) previously reviewed another brand of nitisinone (Orfadin) for the treatment of HT-1; the CADTH Canadian Drug Expert Committee (CDEC) recommended that nitisinone (Orfadin) be reimbursed for the treatment of adult and pediatric patients with an established diagnosis of HT-1 in combination with dietary restriction of tyrosine and phenylalanine if the following conditions are met: the drug is prescribed by a physician with experience in the diagnosis and management of HT-1, and the price is reduced by at least 74%. CDR recently reviewed a third nitisinone product (MDKNitisinone), with a similar recommendation, noting that the cost of MDK-Nitisinone should not exceed the cost of other nitisinone products.

The manufacturer submitted a Markov state–transition model comparing Nitisinone Tablets with diet restriction to diet restriction alone for newborn patients newly diagnosed with HT-1.

Contents

• Abbreviations
• Executive Summary
  • Background
  • Summary of Identified Limitations and Key Results
  • Conclusions
• Information on the Pharmacoeconomic Submission
  • Summary of the Manufacturer’s Pharmacoeconomic Submission
  • Manufacturer’s Base Case
  • Summary of Manufacturer’s Sensitivity Analyses
  • Limitations of Manufacturer’s Submission
  • CADTH Common Drug Review Reanalyses
  • Issues for Consideration
  • Patient Input
  • Conclusions
• Appendix 1. Cost Comparison
• Appendix 2. Summary of Key Outcomes
• Appendix 3. Additional Information
• Appendix 4. Summary of Other HTA Reviews of Drug
• Appendix 5. Reviewer Worksheets
• References

Version: Final

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