EUSA Pharma: NICE Approves the Targeted Cancer Immunotherapy, QARZIBA? (dinutuximab beta) to Treat Children with High-Risk Neuroblastoma

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 websiteviii 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 2018iii 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 2018iv 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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