Nimotuzumab (Theraloc) for glioma - National Horizon Scanning ...

National
Horizon
Scanning
Centre
Horizon Scanning Technology
Briefing
Nimotuzumab
(Theraloc) for glioma
August 2006
This technology briefing is based on
information available at the time of research
and a limited literature search. It is not intended
to be a definitive statement on the safety, efficacy or
effectiveness of the health technology covered
and should not be used for commercial purposes.

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Nimotuzumab (Theraloc) for glioma
Target group
• In children and adolescents:
o First line for diffuse intrinsic pontine glioma.
o Second line for recurrent high-grade malignant glioma, including anaplastic
astrocytoma (AA, grade 3), glioblastoma multiforme (GBM, grade 4) and
pontine glioma.
• First-line for adults with high-grade malignant glioma in combination with
radiotherapy and temozolomide.
Technology description
Nimotuzumab (Theraloc) is an epidermal growth factor antagonist and humanised
monoclonal antibody in phase III trials. Nimotuzumab is administered by a 30-minute
once weekly IV infusion, for adults at a dose of 200-400 mg/m 2 and children 150
mg/m 2 . Nimotuzumab has completed phase II trials for locally advanced and/or
metastatic pancreatic cancer in combination with gemcitabine.
Innovation and/or advantages
Nimotuzumab may provide a further treatment option for high-grade glioma and the
company states that it may reduce the side effects associated with other treatments.
Developer
YM Bioscience and Oncoscience AG (EU marketing partner).
Purpose
Diagnosis or identification of Investigation, assessment or
disease
staging of known disease
Prevention e.g. immunisation, Screening programme or tests to
public health programme
identify latent or early disease
Continuous therapy e.g. dialysis, Patient management and
life support
pathways of care
Service delivery changes Other:
Place of use
Home care e.g. home dialysis
Secondary care e.g. general,
non-specialist hospital
General public e.g. over the
counter
Community or residential care e.g.
district nurses, physio
Tertiary care e.g. highly specialist
services or hospital
Other:
Susceptibility testing for identifying
risk of disease
Individual treatment e.g. drug,
device, procedure, radiotherapy
Rehabilitation
Primary care e.g. used by GPs or
practice nurses
Emergency care e.g. paramedic
services, trauma care
Stage of development and availability in EU/UK
Phase III clinical trials or
Pre-registration in EU (drugs) CE marked, but not yet launched
equivalent
or available in UK
Licence or CE mark application in Licence or CE mark application in Launch or use in UK/EU likely
UK/EU likely within 12 months UK/EU likely within 24 months within 12 months
Launch or use in UK/EU likely Established product, but this is a Other:
within 24 months
new indication in development
Aug 2006 2

Orphan drug status:
Orphan drug status in EU Orphan drug status in USA
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NHS or Government priority area:
Cancer Cardiovascular disease Children
Diabetes Chronic conditions Mental health
Older people Public health Renal disease
Women’s health None identified Other:
Relevant guidance
• Improving outcomes for people with brain and other CNS tumours. NICE, June
2006 1 .
• Improving outcomes in children and young people with cancer. NICE, August 2005 2 .
• Temozolomide for the treatment of recurrent malignant glioma. NICE, April 2001 3
In progress:
• Carmustine implants and temozolomide for the treatment of newly diagnosed highgrade
glioma. NICE, due in March 2007 4 .
Clinical need and burden of disease
Malignant glioma is the most common form of brain tumour, representing 50% to 60%
of all primary brain tumours 3 . There are three main types of glioma – astrocytoma,
ependymoma and oligodendroglioma. Brain tumours are graded according to their
likely rate of growth, from grade 1 (slowest growing) to grade 4 (fastest growing),
with grades 3 and 4 considered high-grade gliomas. Grade 3 astrocytoma is also
known as anaplastic astrocytoma (AA) and grade 4 astrocytoma is also known as
glioblastoma multiforme (GBM).
There are about 3,550 new cases of malignant brain tumour a year in England and
Wales with about 2,700 deaths 1 . Approximately 30% to 35% of malignant gliomas are
AA and 40-45% are GBM 1 . An estimated 1,200 to 1,700 patients in England and
Wales have AA or GBM and may be eligible for nimotuzumab. Median survival time
from diagnosis for GBM is of the order of 5 to 12 months, but for AA is longer at 11
to 36 months 3 .
In the UK, around 400 children and adolescents are diagnosed with a brain or other
central nervous system tumour each year 5 and of these, just over a third are classified
as astrocytoma 6 . Fewer than 40 children a year are diagnosed with pontine glioma 7 .
Children with high-grade glioma invariably have a poor outcome, with 5-year survival
rates of less than 20% for AA and GBM, and median survival of only 9-12 months for
intrinsic brainstem glioma (including pontine glioma) 8 .
Existing comparators and treatments
Adults:
• Surgical resection (rarely curative)
• Radiotherapy
• Chemotherapy e.g. temozolomide, camustine implants
Children:
• Surgical resection (rarely curative)
Aug 2006 3

• Radiotherapy (normally in those three years or over)
• Chemotherapy e.g. cyclophosphamide, vincristine
Efficacy and safety
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Trial name or code Children Children and
young people
Adults
Status Abstract 9
Ongoing Planned
Location Germany Germany, Italy,
Belarus, Russia
Europe
Design - randomised,
controlled, uncontrolled,casecontrol,
case series etc.
Phase II Phase III Phase III
Participants in trial – n=34
number, description,
trial schedule e.g.
placebo or comparator
a . Children with GBM, AA or
intrinsic pontine glioma; progressive
disease following primary or relapse
treatment. Weekly infusion of
nimotuzumab 150 mg/m 2 n=40. Primary Temozolomide
intrinsic pontine vs. temozolomide
glioma
plus
concomitant with nimotuzumab;
for 6 weeks. radiotherapy; concomitant with
Patients with non-progressive disease children and radiotherapy;
received 4 further infusions at 3-week
intervals.
adolescents. adults with GBM.
Follow-up 8 and 21 weeks
Primary outcome Tumour size reduction measured by MRI
Secondary outcomes Clinical deterioration or improvement
Key results o 12 b patients responded (1 partial
response, 11 stable disease) by week 8
o Median change in lesion diameter of
-5% (-39 to +16%).
o At 21 weeks, 5 out of 8 patients were
evaluable for response after additional
therapy: 3 partial responses, 1 stable
disease, 1 c progressive disease. Median
time free of progression was 7.5
months (1.2-13.2 months) d .
Expected reporting date First half 2007 Due to start in
2006
Major adverse effects No severe side effects
Estimated cost and cost impact
The cost of nimotuzumab is yet to be determined.
Potential or intended impact – speculative
For this technology, no barriers to diffusion within the NHS are envisaged.
a 47 patients are now in the trial – company information
b 17 patients have now responded – company information
c 4 patients now have progressive disease – company information
d Median time free of progression is now 9.1 (censored) months (1.2 – 20.5 months) – company information
Aug 2006 4

Patients
Reduced morbidity Reduced mortality or increased
Quicker or more accurate
diagnosis
Services
Increased use e.g. length of stay,
out-patient visits
Decreased use e.g. shorter length of stay, reduced
referrals
Costs
Increased unit cost compared to
alternative
Savings:
Unknown:
References
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Improved quality of life for patients
survival
and/or carers
Earlier identification of disease Changed pathway of care or
outcome
Service reorganisation required Staff or training required
Increased costs: more patients
coming for treatment
Increased costs: capital
investment needed
1 Improving Outcomes for people with brain and other CNS Tumours, National Institute for Health and Clinical
Excellence. The Manual. June 2006
2 Improving outcomes in children and young people with cancer, National Institute for Health and Clinical
Excellence. The Manual. August 2005
3 Temozolomide for the treatment of recurrent malignant glioma (brain cancer), National Institute for Health and
Clinical Excellence. Number 23, April 2001.
4 Final Appraisal Determination: Glioma (newly diagnosed and high grade) - Carmustine implants and
temozolomide, National Institute for Health and Clinical Excellence, April 2006
5 Cancer Research UK, data for 2002, http://info.cancerresearchuk.org/cancerstats/types/brain/incidence
(accessed 6/7/2006)
6 Cancer Research UK, http://info.cancerresearchuk.org/cancerstats/childhoodcancer/incidence/#brain (accessed
6/7/2006)
7 The Royal Marsden NHS Foundation,
http://www.royalmarsden.nhs.uk/RMH/cancer/paediatriccancers/pontineglioma/?wbc_purpose=Basic
(accessed 5/7/06)
8 The Institute of Cancer Research.
http://www.icr.ac.uk/research/research_sections/paediatric_oncology/paediatric_oncology_teams/molecular_pa
thology/gliomas/index.shtml (accessed 6/07/2006)
9 Bode U, Buchen S, Janssen G et al., Results of a phase II trial of h-R3 monoclonoal antibody (nimotuzumab) in
the treatment of resistant or relapsed high-grade gliomas in children and adolescents. American Society of
Clinical Oncology, 2006, abstract no. 1522
The National Horizon Scanning Centre is funded by the Research and Development Division
of the Department of Health, England
The National Horizon Scanning Centre,
Department of Public Health and Epidemiology
University of Birmingham, Edgbaston, Birmingham, B15 2TT, England
Tel: +44 (0)121 414 7831 Fax +44 (0)121 414 2269
www.pcpoh.bham.ac.uk/publichealth/horizon
Aug 2006 5