Dinutuximab beta - the process

As many of you may know, after over three years of hard negotiation, Dinutuximab beta was finally approved for routine commissioning across the United Kingdom for treating high-risk neuroblastoma in people aged 12 months and over.

Dinutuximab beta is a chimeric monoclonal antibody that targets GD2, a glycolipid overexpressed in certain tumours such as neuroblastoma. The immunotherapy drug recognises cells expressing a receptor (GD2) on their surface, and signals for the immune system to destroy these cells. Because the drug has to make contact with tumour cells, this immunotherapy is suited to mopping up small populations of residual cells rather than penetrating the primary tumour or large metastases. Hence immunotherapy is used to help eradicate any residual disease and increase the chances of keeping children in remission.

Although Dinutuximab beta had effectively become standard of care across the world and in the UK through the SIOPEN trial, gaining market approval through both NICE and the SMC was a challenge due to the Orphan nature of the treatment where developing a drug intended to treat a rare disease does not allow the recovery of the capital invested for its research.

The NICE appraisal process looks at both the clinical and cost effectiveness of all new treatments. From a clinical perspective, how well does the treatment under appraisal compare with current treatments. For example, does it have improved efficacy? Does it have fewer side effects? In respect of cost effectiveness, does it represent value for money for the public purse compared with other NHS treatments. Any new treatments must come from within existing budgets so, if a new treatment is commissioned, then savings or reductions will need to be made elsewhere. For this reason, the NICE process must evaluate the opportunity cost. Does the introduction of the new treatment outweigh the possible cuts required?

To determine this NICE use QALYs (Quality Adjusted Life Years) which look at the quality of life against the length of life and ICERs (Incremental Cost Effectiveness Ratio) which analyses the difference in cost divided by the difference in their effect. By using these formulae, NICE are able to set a standard against which treatments can be fairly evaluated even if they are significantly different presentations or conditions.

Unfortunately, although Orphan drugs regularly fulfil the clinical effectiveness aspect with improved efficacy, they are often extremely expensive on a per patient basis and fail to achieve the cost effectiveness benchmark. This was the case with Dinutuximab beta. When it was first presented to NICE for appraisal, it was rejected as not being cost effective.  The decision was taken to appeal on technical grounds. The appeal was upheld and a new appraisal instigated. Although there was a huge amount of goodwill, the issues affecting the initial evaluation remained. After many weeks of deliberations, EUSA Pharma submitted a proposal under the Patient Access Scheme which enabled the treatment to proceed through routine commissioning.

Although only covered in a few lines here with the technical details removed, the efforts of all parties concerned in coming to a successful outcome cannot be over exaggerated. EUSA, NICE, NHS England, the clinical experts and the charities concerned including Neuroblastoma UK, who acted as patient experts at the appraisal, worked tirelessly to find a solution. Having completed the NICE process, a similar process was undertaken with the Scottish Medicines Consortium (SMC) which thankfully received a similar outcome.

Going forward, although we understand the rationale for the assessment for new drugs, the NICE one-size fits all approach is disadvantageous for rare diseases such as Neuroblastoma. Although each individual Orphan disease affects a relatively small number of people, when added together it is estimated that 6 million people in the UK fall into this category. We believe the appraisal process needs to be reviewed with either a higher financial threshold or an alternative process developed for this specific patient group.

Tony Heddon, Chair, Neuroblastoma UK