EUSA-PHARMA

EUSA Pharma today welcomed a decision by the National Institute for Health and Care Excellence (NICE) to recommend the use of the targeted cancer immunotherapy, QARZIBA^® (dinutuximab beta) to treat children with high-risk neuroblastoma within the NHS in England and Wales.ⁱ High-risk neuroblastoma is an aggressive form of neuroblastoma – the most common solid tumour of childhood that originates outside of the brain.ⁱⁱ Dinutuximab beta is the first targeted cancer immunotherapy approved for use on the NHS to treat this disease. It has been shown in a post-hoc analysis to improve overall survival (OS) outcomes compared to historically treated patients who did not receive immunotherapy as part of their care. Dinutuximab beta, when used in the maintenance phase of treatment for patients who did not receive prior immunotherapy, is also used to keep this cancer from returning or progressing in some children with high-risk neuroblastoma.ⁱⁱ

“Today’s decision by NICE is a vital step forward in the treatment of young children with this aggressive type of cancer ,” said Dr Juliet Gray, Associate Professor in Paediatric Oncology at the Cancer Immunology Centre, University of Southampton. “By harnessing the body’s own immune system, dinutuximab beta has shown it can target and attack this cancer very effectively in some patients. For some children this could mean extra weeks or months with their families, for others it may even lead to them becoming cancer-free for a long period of time .”

Dinutuximab beta is a monoclonal antibody (a type of protein) that binds to a specific target which is overexpressed on neuroblastoma cells, called GD2.ⁱⁱⁱ This induces dual immune mechanisms that then enable the immune system to lead the destruction of neuroblastoma cancer cells.ⁱⁱ In the key phase III clinical study (APN311-302), a post hoc comparison of dinutuximab beta, used in the maintenance phase of the first-line treatment of high-risk neuroblastoma (n=367) , showed improved survival outcomes, with a 12% improvement in OS rate at three years versus using no immunotherapy in a historical control group of similar patients (n=450).ⁱⁱ The dinutuximab beta treated patients had an OS rate of around 65% at 5 years versus 50% compared to the historical control group (p=<0.0001).ⁱⁱ

Tony Heddon, Chair of Neuroblastoma UK commented: “Ensuring that children and families facing high-risk neuroblastoma have access to the medicines and care they need is absolutely critical. Today’s recommendation is a bold and forward-thinking decision from NICE and we applaud them, EUSA Pharma and all those across the community who have worked together to make this medicine available. This decision offers the hope that these children with high-risk neuroblastoma, may now have a better future in front of them .”

On average, every week, two families in the UK will learn that their child has neuroblastoma, with approximately 100 children diagnosed each year.^iv It is the most frequently-occurring solid tumour in infants under the age of one, accounting for around a fifth (22%) of all cancers diagnosed at this age.^v Children with high-risk disease to whom this approval applies, account for approximately 40% of all neuroblastoma cases.^vi Children with high-risk neuroblastoma typically undergo many rounds of complex and intensive treatment, usually comprising several cycles of chemotherapy, surgery, stem cell transplant and radiotherapy.^vii

The recommendation from NICE within its Final Appraisal Determination (FAD) is that dinutuximab beta be used as an option for treating high-risk neuroblastoma after at least a partial response from induction chemotherapy, followed by myeloablative therapy and stem cell transplant in people aged 12 months and over, if the person has not had previous anti-GD2 immunotherapy.ⁱ

Lee Morley, CEO of EUSA Pharma added: “Today’s decision is the result of strong collaboration between NICE, EUSA Pharma and the neuroblastoma community, who have each worked tirelessly to ensure that every eligible child has the option to benefit from this potentially life-changing treatment. Our long-standing commitment has always been to secure access to dinutuximab beta for all eligible children with high-risk neuroblastoma, across the UK and today’s decision is a key part of that journey. Beyond England and Wales, we are continuing to work closely with the Scottish and Northern Irish health authorities with the aim of making this medicine available in those countries as quickly as possible .”

- ENDS -

NOTES TO EDITORS

About dinutuximab beta

How it works

Dinutuximab beta is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a tumour-associated carbohydrate structure, called GD2, which is present in high amounts on the surface of neuroblastoma cells.ⁱⁱ When dinutuximab beta attaches to the neuroblastoma cells, it induces dual immune system mechanisms (the complement-dependant and antibody-dependant cell-mediated immune pathways) and makes them a target for the body’s immune system. This then mounts an attack to kill the cancer cells, using the body’s natural killer immune cells, and the complement protein system.ⁱⁱ

Its development and approval

Dinutuximab beta is the result of a considered science–pharma collaboration. Dinutuximab beta was developed by Apeiron Biologics with a number of partners (in particular the SIOPEN academic neuroblastoma group) and acquired by EUSA Pharma in 2016, to bring the treatment to market. Dinutuximab beta received European approval in May 2017, first under the brand names dinutuximab beta Apeiron and Dinutuximab beta EUSA and subsequently under its new name, QARZIBA^® , approved by the European Medicines Agency in November 2017.ⁱⁱⁱ

How it is taken

Dinutuximab beta is given as an infusion (drip) into a vein. Each course of treatment with the medicine is given for 5 or 10 days every 35 days. It is given for a total of 5 courses. The recommended dose depends on the patient’s weight and height.ⁱⁱⁱ

Data supporting its use

Dinutuximab beta has been investigated in a number of clinical trials for high-risk neuroblastoma.ⁱⁱ During the NICE appraisal, the primary clinical evidence came from APN311-302, a multinational, open-label, randomised, controlled Phase III trial comparing dinutuximab beta plus isotretinoin (n=189) with dinutuximab beta plus isotretinoin plus interleukin-2 (n=190).^i,ii The primary outcome in the trial was event-free survival at three years (disease progression or relapse, death and secondary tumour defined as events) with OS, overall response, and incidence of relapsed or refractory disease included as secondary outcomes.ⁱⁱ This study consisted of up to five different comparison phases, one of which was treatment with dinutuximab beta with or without interleukin-2 (IL-2) during the maintenance phase , in the first line setting.ⁱⁱ

In APN311-302, the 3-year event free survival (primary endpoint) showed rates of 55% without IL-2 and 61% with IL-2 (p=0.3202) while the 3-year OS rates were 64% and 69%, respectively (p=0.6114).ⁱ A comparison to an historical control group obtained from an earlier patient enrolment within the APN311-302 study (between 2002 and 2010) was performed using 450 high-risk neuroblastoma patients, who did not receive immunotherapy. Given the relatively high number of patients it is expected that these patients are representative of patients with high-risk neuroblastoma seen in clinical practice during this period. This comparison showed that the percentage of patients that were still alive after three years of follow-up was 12% higher after dinutuximab beta treatment (with or without IL-2) than for patients who did not receive immunotherapy, a difference considered clinically relevant.ⁱⁱ It also showed an OS rate of around 65% at 5 years with dinutuximab beta versus 50% in the historical control group (p=<0.0001).ⁱⁱ

At marketing authorisation, the European Medicines Agency considered that the available data set was not comprehensive and that measures were necessary to generate additional efficacy and safety data. EUSA Pharma is committed to this and is continuing to collect further data to widen the body of efficacy and safety information available on this medicine.ⁱⁱ

Side effects

Side effects with dinutuximab beta are common. In general, the most common side effects with dinutuximab beta (which may affect more than 7 in 10 people) are pyrexia (fever) and pain. Other side effects (which may affect more than 3 in 10 people) are hypersensitivity (allergy), vomiting, diarrhoea, capillary leak syndrome (leakage of fluid from blood vessels that can cause swelling and a drop in blood pressure) and hypotension (low blood pressure).ⁱⁱⁱ

In the APN311-302 study, 98.9% of patients (362 of 366) in both treatment group experienced toxicities. Serious adverse events were reported more frequently in patients receiving IL-2 (46% of 183 patients) compared to patients not receiving IL-2 (27% of 183 patients). Serious adverse events leading to discontinuation of treatment were more frequent in the IL2 arm than the group without IL2,17% vs 6% of patients, respectively.ⁱⁱ

Further details of side effects can be found in the Summary of Product Characteristics on the EMA website^viii http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003918/human_med_002104.jsp&mid=wc0b01ac058001d124

About EUSA Pharma

Founded in March 2015, EUSA Pharma is a specialty pharmaceutical company with commercial operations across Europe and the USA and a wider distribution network in approximately 40 further countries. The management team comprises highly-experienced pharmaceutical professionals with a proven track record of successfully identifying, developing and commercialising innovative medicines that advance patient care and improve their wellbeing. For more information visit: http://www.eusapharma.com .

References

ⁱ NICE Final Appraisal Determination (FAD) for dinutuximab beta for treating neuroblastoma.
ⁱⁱ QARZIBA Public Assessment Report. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003918/WC500227726.pdf Accessed July 2018
ⁱⁱⁱ QARZIBA EPAR – Summary for the public. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003918/WC500227727.pdf Accessed July 2018
^iv Cancer Research UK: About Neuroblastoma. Key fact available at https://bit.ly/2NjdR2b Accessed July 2018.
^v Cancer Research UK: Children’s cancers. Children’s SNS tumour incidence. Available at https://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers/incidence#heading-Eleven Accessed July 2018.
^vi NICE dinutuximab beta committee papers. Available at https://www.nice.org.uk/guidance/gid-ta10069/documents/committee-papers Accessed July 2018.
^vii Cancer Research UK – neuroblastoma treatment by risk group. Key fact available at https://www.cancerresearchuk.org/about-cancer/childrens-cancer/neuroblastoma/treatment-risk-group Accessed July 2018.

^viii QARZIBA SmPC – Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003918/WC500227724.pdf Accessed July 2018.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcardreporting . Adverse events should also be reported to EUSA Pharma. Email: safety@eusapharma.com Fax: +44(0)3305 001167

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