Package advice atidarsagene autotemcel (Libmeldy®) for the treatment of metachromatic leukodystrophy (MLD)

Registered indication

Reimbursement is requested for the treatment of metachromatic leukodystrophy (MLD). MLD is an autosomal recessive inherited lysosomal storage disorder caused by mutations in the ARSA gene, resulting in a deficient activity of the lysosomal enzyme arylsulfatase A (ARSA), clinically divided into 3 morbidity types, depending on the time of diagnosis:

• late infantile (LI) (≤30 months); 
• juvenile (with early juvenile (EJ) 30 months -≤ 7 years and late juvenile 7-≤16 years); and 
• adult (age at onset after 16 years).

This is a very serious hereditary metabolic disease in which the storage of certain fats causes the destruction of myeline, which protects the nerve cells. This creates a progressive disease that results in intellectual disability and deterioration of motor skills. The most severely affected patients die from the disease within a few years after the onset of symptoms. 

Package advice

From various parties, including the physicians' association, we have received signs that they would like atidarsagene autotemcel to be available for some specific early-symptomatic patients. For these patients, the National Health Care Institute cannot conclude, on the basis of the study data, that treatment meets the established medical science and medical practice (because of insufficient data). 

For treatments that do not (yet) meet the established medical science and medical practice, the conditional admission (VT) of orphan drugs, conditionals and exceptionals can be applied. The National Health Care Institute is keen to work, with all relevant stakeholders, to see whether this would be an appropriate route to make atidarsagene autotemcel available to a specific group of early-symptomatic patients.

The National Health Care Institute advises the Minister to include atidarsagene autotemcel in the basic health insurance package for presymptomatic patients, provided that a price reduction is achieved and pay-for-performance agreements are made. The Insured Package Advisory Committee (ACP) takes the view that a price above the reference value is socially prudent in this unique case:

• young children who suffer from a very serious condition and who often die young without treatment; 
• with a condition that is ‘ultra rare’ (no more than 2-3 patients per year); 
• a treatment with a limited total budget impact. 

A pay-for-performance agreement should ensure that the risk of payment for patients who do not respond adequately to the treatment is borne by the manufacturer and not by society. 

In addition, the National Health Care Institute will draw up an orphan drug arrangement in consultation with the physicians' association and other relevant parties. This arrangement will also take into account the starting criteria. Agreements on the international indication committee and international data collection and analysis will also be registered in the orphan drugs arrangement.

The National Health Care Institute carried out the assessment within the ‘Beneluxa Initiative’ and collaborated with Belgium and Ireland. 

This report is a summary of recommendations by the National Health Care Institute. The original text is in Dutch.