Package advice for the lock procedure drug betibeglogene autotemcel (Zynteglo®)

Zorginstituut Nederland has completed its assessment whether betibeglogene autotemcel (Zynteglo®, hereinafter “beti-cel”) can be included in the insured package. Beti-cel is indicated for the treatment of patients aged 12 and older with transfusion-dependent beta thalassaemia (TDT). The reason for this advice was the placing of beti-cel in the so-called ‘lock procedure’ for expensive medications. Beti-cel is an innovative, promising, one-time treatment that addresses the cause of the disease and is in line with established medical science and medical practice. However, there are uncertainties about the long-term effects. Furthermore, the cost-effectiveness based on the available data is uncertain and as yet unfavourable. A price reduction of 35 per cent is needed if it is going to be possible to call this a cost-effective treatment. Moreover, the Zorginstituut recommends a pay-for-performance agreement with the marketing authorisation holder. 

Registered indication

Zynteglo® (beti-cel) is indicated for treating patients aged 12 and older with transfusion-dependent beta thalassaemia (TDT) who do not have a β0/β0 genotype and for whom transplantation of haematopoietic stem cells (HSC) is appropriate but no related HLA-compatible (human leukocyte antigen) HSC donor is available. 

Beta thalassaemia is a form of hereditary anaemia; the condition is one of those tested for in neonatal blood spot screening. In more severe forms, the patient is dependent on regular blood transfusions. The numerous blood transfusions mean that patients are at high risk of serious iron accumulation. This iron accumulation can affect vital organs and patients then need iron chelators as a standard therapy. The only curative treatment option is correcting the underlying defect by allogenic haematopoietic stem cell transplantation (HSCT). The majority of patients with beta thalassaemia are not eligible for this. 

Established medical science and medical practice

The Zorginstituut concludes that beti-cel is in line with established medical science and medical practice for treating patients aged 12 and older with transfusion-dependent beta thalassaemia (TDT) who do not have a β0/β0 genotype and for whom transplantation of haematopoietic stem cells (HSC) is appropriate but no related HLA-compatible (human leukocyte antigen) HSC donor is available. After treatment with beti-cel, the majority of patients achieve a level of haemoglobin that means they are no longer dependent on blood transfusions.
 

Zorginstuut's advice

Beti-cel is an innovative, promising, one-time treatment that addresses the cause of the disease and is in line with established medical science and medical practice. However, there are uncertainties about the longer-term effects: whether being independent of transfusions or a reduced need lasts a lifetime, how quickly use of iron chelators can be stopped, and what the effect is on complications related to beta thalassaemia. Furthermore, the cost-effectiveness based on the available data is uncertain and as yet unfavourable. Data that will be collected in future by the physicians’ association and the marketing authorisation holder will provide more information about this.

The Zorginstituut advises the Minister to include beti-cel in the health insurance package if the following conditions are met:

  • Based on the above-mentioned uncertainties, the risk of overpricing should not be placed exclusively with those paying the premiums. A price reduction of 35 per cent is needed if it is going to be possible to call this a cost-effective treatment. 
  • Moreover, the Zorginstituut recommends a pay-for-performance agreement with the marketing authorisation holder in which payment depends on whether or not relevant outcome measures are achieved. The marketing authorisation holder has made two proposals for such an arrangement. The following relevant outcome measures may be part of that agreement: 
    • dependence on transfusions or not; 
    • use of iron chelators.

The Zorginstituut advises the Minister to enter into the (price) negotiations within the already existing Beneluxa collaboration. In 5 years’ time, the Zorginstituut could reassess how the cost-effectiveness has developed on the basis of the data available. 

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