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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