Package advice onasemnogene abeparvovec (Zolgensma®) for the treatment of SMA
Zorginstituut Nederland has completed its assessment whether onasemnogene abeparvovec (Zolgensma®) for the treatment of patients with symptomatic spinal muscular atrophy (SMA) can be included in the insured package. The reason for this advice was the placing of Zolgensma in the so-called lock procedure for expensive medicines. Onasemnogene abeparvovec (OA) is an innovative, promising and one-time treatment. The first results are promising, however, there are also great uncertainties about the effects, both in the short and long term and about the possible use of additional disease-modifying treatments. Furthermore, the cost-effectiveness based on the available data is uncertain and as yet unfavourable. The Zorginstituut advises the Minister to include OA in the health insurance package only after price negotiations and a ‘pay for performance’ agreement with the marketing authorisation holder.
The indication of OA as determined by the EMA includes the treatment of:
- patients with 5q spinal muscle atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1;
- patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene.
Patients with SMA have a defect in the SMN1 gene. The body needs this gene to produce a protein that is essential for the normal functioning of the nerves that control muscle movements. The active substance in OA contains a functional copy of this gene. When injected, the product (through an AAV vector) passes into the nerves from where it delivers the right gene to produce sufficient protein to safeguard the nerve function. This gene therapy is very important for the treatment of this life-threatening condition in very young children.
Established medical science and medical practice
The Zorginstituut, the Belgian Committee for the Reimbursement of Medicinal Products (CTG) and the Irish National Centre for Pharmacoeconomics (NCPE) conclude that OA meets the established medical science and medical practice for the treatment of symptomatic patients with SMA type 1. The mechanism of action, the broad consensus on the benefits of a presymptomatic treatment and the fact that more than half of patients with 3 copies of SMN2 will possibly develop a very serious disease, are considered sufficient to conclude that OA also meets the established medical science and medical practice for presymptomatic SMA patients with 2 or 3 copies of the SMN2 gene.
There is insufficient evidence to draw definitive conclusions on the effectiveness of OA compared to nusinersen. A good comparative study comparing OA with nusinersen has not been carried out and will probably not be carried out in the future.
The net budget impact of OA in year 3 will be approximately €11 million in the Netherlands. The cost-effectiveness is determined for a subgroup of patients within the registered indication, i.e. symptomatic patients with SMA type 1. Presymptomatic patients are included in a scenario analysis.
The added value of OA in relation to nusinersen cannot yet be determined because comparative effectiveness data are missing. The Beneluxa countries could not agree with the assumptions made in the model by the marketing authorisation holder and had an alternative ‘base case’ analysis performed, which included the use of nusinersen after administration of OA. The estimate of this ‘incremental cost effectiveness ratio’ (ICER) shows that OA is not cost-effective versus nusinersen or best support care (BSC); the estimated ICER is €263,389 per QALY versus nusinersen. In a previous assessment, the cost-effectiveness of nusinersen was determined for the above indication. The price for nusinersen has been negotiated by the Minister. Because this information is not public, the Zorginstituut has itself drawn up a scenario for the current assessment of OA's cost-effectiveness, based on the price of nusinersen recommended at the time (a price decrease of 85% to approach the reference value). In that case, the price of the OA must decrease by 91% to fall within the reference value of €80,000 per QALY.
OA is an innovative, promising and one-time treatment that addresses the cause of the disease and meets the established medical science and medical practice. The first results are promising; pre-symptomatic treatment seems to prevent the disease. That is valuable. However, there are also great uncertainties about the effects, both in the short and long term and about the possible use of additional disease-modifying treatments. Furthermore, the cost-effectiveness based on the available data is uncertain and as yet unfavourable. Data collected in the future in the existing SMA register will provide more information about this.
The Zorginstituut advises the Minister to include OA in the health insurance package when the following conditions are met:
- On the basis of the above-mentioned uncertainties, the risk of overpricing should not be placed exclusively with those paying the premiums. Taking into account a price reduction of 85% for nusinersen (the current treatment) and uncertainty about effectiveness, a price reduction of 91% should apply to OA to arrive at a cost-effective treatment with OA. If the marketing authorisation holder's claim is fully realised, no price reduction would be necessary. If that risk were shared, a price reduction of approximately 50% would be required.
- In addition, the Zorginstituut recommends a ‘pay for performance’ agreement whereby the payment depends on whether or not relevant outcome measures are reached, like ventilation-free survival or reaching motor skill milestones.