GVS assessment of givosiran (Givlaari®) for the treatment of acute hepatic porphyria

Zorginstituut Nederland has completed its assessment whether givosiran (Givlaari®) is interchangeable with a product that has been included in the Medication Reimbursement System (GVS). Givosiran (Givlaari®) is indicated for the treatment of acute hepatic porphyria (AHP) in adults and adolescents who are 12 years and older. Givosiran has a therapeutic added value compared to the standard treatment (best supportive care). The Zorginstituut's recommends that givosiran (Givlaari®) be included in List 1B of the GVS, provided that the conditions of a substantial price reduction are met and agreements are made for appropriate use and evaluation of the effectiveness and safety in the long term. 

Registered indication

Givosiran (Givlaari®) is indicated for the treatment of acute hepatic porphyria (AHP) in adults and adolescents who are 12 years and older. The marketing authorisation holder has requested reimbursement for a specific group within the registered indication: for the treatment of acute hepatic porphyria in patients with a confirmed diagnosis of acute hepatic porphyria and a recent history of frequent acute porphyria attacks (≥ 2 acute attacks over 6 months or on hemin prophylaxis). An acute porphyria attack is accompanied by severe pain and has a significant negative impact on the daily functioning of a patient with acute hepatic porphyria. 

Assessment

The decrease in the number of acute porphyria attacks due to treatment with givosiran is a possible explanation for the observed decrease in pain and the positive effect of givosiran on various aspects of quality of life. Whether there is a significant reduction in pain between the attacks has not been demonstrated. In addition, no effect of givosiran on other chronic symptoms, such as fatigue and nausea, has been demonstrated. There is no evidence for a beneficial effect of givosiran on (preventing) long-term complications such as kidney disease and liver disease. 

The Zorginstituut assessed givosiran on the basis of the four package criteria: effectiveness, cost-effectiveness, necessity and feasibility. Inclusion of givosiran for the indicated indication will result in €8 to €11 million per year. This is based on an estimate of 15-21 patients in the third year who will be treated with givosiran.

Zorginstituut's advice

The Zorginstituut has concluded that givosiran (Givlaari®) is not interchangeable with another product included in the GVS. Givosiran has a therapeutic added value compared to the standard treatment (best supportive care). The Zorginstituut recommends that givosiran (Givlaari®) be included in List 1B of the GVS, provided that the following conditions are met:

  • A substantial price reduction of givosiran, given the high cost per patient and unfavourable cost-effectiveness. 
  • Appropriate use criteria for the efficient application of the treatment. The Zorginstituut is already discussing the making of arrangements for appropriate use with the professional group. In this respect, the Zorginstituut also recommends that the optimal dosage be assessed, to see whether this can further improve the cost-effectiveness.
  • The monitoring of long-term outcomes to evaluate the effectiveness and safety of givosiran. Regie op Registers is the recommended practice for this. The Zorginstituut will advise the parties concerned to agree to this practice.

If the application of givosiran (Givlaari®) is included in the package after a successful price negotiation, the Zorginstituut recommends the following compensation conditions: exclusively for the treatment of acute hepatic porphyria in patients with a confirmed diagnosis of acute hepatic porphyria and a recent history of frequent acute porphyria attacks (≥2 acute attacks over 6 months or on hemin prophylaxis).

This report is a summary of recommendations by Zorginstituut Nederland. The original text is in Dutch.