Update on the NICE Technical Assessment of Neuroblastoma (high risk) – Dinutuximab beta EUSA

On 23rd November, at their offices in Manchester, the National Institute for Health and Care Excellence (NICE), which is responsible for providing evidence-based guidance on which treatments and drugs are available in the NHS, undertook an initial technical appraisal of Dinutuximab beta immunotherapy for treating high-risk neuroblastoma.

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 thought to be 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 hopefully increase the chances of keeping children in remission.

Dinutuximab has been available in the UK over the last few years as part of the SIOPEN (an international research collaboration) High Risk and Long-Term Infusion trials. Patients with high risk disease who have achieved a sufficiently good response at the end of surgery, intensive chemotherapy and stem cell transplant, and have completed this treatment within specified time lines, have been eligible to receive the anti-GD2 antibody as part of the High-Risk study. Those children who haven’t been able to receive the antibody through the High-Risk study, including those children with relapsed neuroblastoma, have generally been eligible to receive antibody through the Long-Term Infusion study.

The SIOPEN Long Term Infusion study closed in January 2017, and the High-Risk Trial closed to recruitment of new patients in June 2017. While the NICE process for Dinutuximab evaluation continues, immunotherapy will continue to be provided within the High-Risk Trial, to patients already enrolled who respond well enough to receive the antibody as part of the trial.

NICE have a defined set of outcome measures that they consider including overall survival, event free survival, adverse effects of treatment, health-related quality of life and the cost effectiveness of the treatment. The appraisal in Manchester was arranged to discuss the response of NICE’s evidence research group’s (ERG) to a presentation prepared by EUSA as to the clinical and cost effectiveness of Dinutuximab beta. EUSA Pharma are seeking a marketing authorisation in the UK. A similar antibody has already been approved by the European Medicines Agency and in the United States and is available to patients.

As well as two representatives from EUSA pharma, there were four other experts invited to represent the views of patients, parents and the Neuroblastoma clinical community:

  • Juliet Gray, Consultant Oncologist, Southampton
  • Martin Elliott, Consultant Oncologist, Newcastle
  • Tony Heddon, Deputy Chair, Neuroblastoma UK
  • Nick Bird, Acting Chair, Solving Kids Cancer

The NICE committee consisted of 48 members from a broad spectrum of NHS interest groups. The ERG interrogation of the presentation was most robust with their response running to over 60 pages. Although the content and output of the presentation is confidential, the nature of the treatment and the patient group to which it is targeted, makes consistent modelling of outcomes a challenge especially with the added complication of the treatment having recently transferred ownership from Apeiron to EUSA.

After the appraisal Tony Heddon, who represented Neuroblastoma UK said “It was a very detailed session and the team who represented the clinical and patient communities were heavily involved in the discussion. We had the opportunity to present our views, answer questions and comment on all aspects of the appraisal. At the end of the of the 4-hour session, our input was welcomed by the committee and there was a great deal of goodwill towards us, but it was recognised that further modelling and responses were required from EUSA pharma to ensure that the NICE outcome measures were met. It is a very challenging process and there are significant hurdles that need to be jumped before we can contemplate a successful outcome”.

Tony would like to thank all those who helped him prepare for the meeting especially the parents of those children affected by Neuroblastoma whose input was invaluable. The NICE process is expected to continue until May 2018