Anti-GD2 antibody therapy update, December 2017

Isqette | APN311 | dinutuximab beta | ch14.18/CHO

Isqette™ or dinutuximab beta was originally developed by APEIRON Biologics and sold to EUSA Pharma, a UK company.

Dinutuximab beta is the so-called European anti-GD2 antibody, used in clinical trials conducted by the SIOPEN collaborative research group, which includes the UK.

In May 2017 dinutuximab beta was granted European Medicines Agency (EMA) approval under exceptional circumstances. This means that the information about the safety and efficacy of dinutuximab beta was deemed incomplete. Each year the EMA will receive an update from the company and review their decision as necessary. The details of the decision.

In the UK, the first meeting of the National Institute for Health and Care Excellence (NICE) to appraise dinutuximab beta was held on 23rd November in Manchester. Solving Kids’ Cancer was once again represented by trustee and neuroblastoma parent, Nick Bird. Nick was ideally placed having been through the entire process with Unituxin™ (dinutuximab); including our successful appeal, on human rights grounds and unfair evaluation of the scientific evidence, against NICE’s decision not to recommend it for approval.

A final decision about whether to recommend dinutuximab beta for use on the NHS – meaning it can simply be prescribed by treating clinicians, is not expected until May 2018. Provisional guidance will be issued before that, and we hope to be able to provide another update when this happens.

Unituxin | dinutuximab | ch14.18/SP2/0

Due to manufacturing supply issues Unitixun™, manufactured by United Therapeutics Corporation (UTC) in the United States of America, is not available anywhere outside of North America. All commercialisation of this antibody in Europe has been ceased. It is now considered unlikely that it will ever be approved for use in Europe, including the UK.

Impact on children with high-risk neuroblastoma in the UK

Children in the United Kingdom who have already been enrolled on HR-NBL1, the European-wide SIOPEN high-risk neuroblastoma trial will be able to receive antibody in combination with 13-cis-retinoic acid during the maintenance phase of treatment, provided they meet the response time criteria written into the trial. The aim of the maintenance phase, given at the end of all other treatments, is to seek to prevent a patient’s disease from coming back or starting to grow again. For children diagnosed since June, after the closure of the high-risk trial, there is uncertainty surrounding the availability of antibody when this would normally be scheduled to begin – which for the first of these patients will be around February/March time.

Similarly, there is also uncertainty surrounding the availability of antibody for children who were enrolled on the high-risk trial but take too long to reach the maintenance phase, and are therefore not eligible to receive antibody as part of the trial. This is generally either because children respond more slowly to induction chemotherapy, or they experience complications that necessitate delays in treatment.

There is also uncertainty surrounding the availability of antibody for children who have relapsed but have never previously received antibody as a component of maintenance therapy.

It should be stressed that although the availability of antibody is not guaranteed, as of today this is the current situation regarding access to the antibody as a maintenance treatment:

• No child in the UK has thus far been unable to receive the antibody at the point of need.
• No parent has been required to fund antibody treatment privately.
• No UK clinician has been unable to obtain antibody for a patient who they believed could benefit from receiving it.

A lot of work has taken place behind the scenes by clinicians and other stakeholders to try to ensure that this has been, and remains, the case. It is hoped that the situation will never arise where a child is unable to receive antibody without it having to be funded privately, but it cannot be altogether ruled out.

Moreover, going forward, unless dinutuximab beta is approved by NICE for use on the NHS, this will certainly not continue to be the case. A decision not to recommend dinutuximab beta will mean it, and therefore anti-GD2 antibody therapy, becomes unavailable in England and Wales on the NHS – and likely the rest of the UK too.

In the period between now and whenever NICE make their final decision, outside of the high-risk trial, provision of antibody for each child at the point of need remains a matter for that child’s clinician to manage. Guidelines have been issued to all UK treatment centres on the processes that need to be followed in such situations.