This document discusses pricing and reimbursement tactics for several drugs: 1. It outlines the Glivec indications approved from 2002-2007, the clinical trial data supporting each approval, and the improvement in medical benefit (ASMR) rating given in France. 2. It also discusses pricing and reimbursement for Avastin combinations in several countries from 2005-2008. 3. Information is provided on MabThera approvals for lymphoma and leukemia in the UK and France from 2003-2010. 4. Finally, pricing and reimbursement decisions are summarized for Sutent, Nexavar, and other drugs in the UK, France, and Scotland from 2006-2010.

1. Pricing and Reimbursement
Mapping Tactics
Majed Elhewaihi, DrPH

2. Glivec Indications Year Clinical data ASMR
1. Adult patients with Kit positive unresectable
and/or metastatic malignant GIST
2002 Pop: 300-360
Open multicentre phase II trial
Primary endpoint: OR, RR
I
2. Newly diagnosed (bcr-abl) (Ph+) (CML) for whom
BMT is not considered as the first line of
treatment
2003 Pop: 390-465 SOC= IFN /Cytarabine
1 phase III trial: Glivec vs IFN + ARA-C
Primary endpoint: DFS (at 12 months 97.2vs 80.3%)
Secondary endpoint: Hematologic RR
I
3. Ph+ CML in chronic phase after failure of IFN
4. Or in accelerated phase or blast crisis
2004 Pop: + 600 / year SOC= IFN /Cytarabine
3 non comparative trials
- OS: 90%+ at 2 years(~3-5)
- RR: 46,2% vs. 25-30% I
II
5. Newly diagnosed (Ph+ ALL) under chemo
6. And patients with relapsed or refractory Ph+ ALL
as monotherapy
2007 Pop: + 130-220 /year SOC = antineoplasic
- 4 trials vs chemo (hematologic RR)
- 1 trial non comparative (hematologic RR)
I
II
7. Adult patients with MDS/MPD associated with
PDGFR gene re-arrangements
2007 Pop +15-30 / year Non comparative phase II
trial
(hematologic RR)
III
8. Adult patients with advanced HES and/or CEL
with FIP1L1-PDGFRα rearrangement
2007 + 6 / year
Non comparative phase II trial (hematologic RR)
III
9. Adult patients with unresectable DFSP and
patients with recurrent and/or metastatic DFSP
who are not eligible for surgery
2008 + 15-30 / year
Non comparative phase II trial (objective RR) IV
P&R country tactics - MAJED ELHEWAIHI
GLIVEC

3. Regimen Avastin+5FU+irinoteca
n
Avastin+paclitaxel Avastin+FOLFOX
Indication 1st line metastatic
colorectal cancer
1st line breast cancer 2nd line metastatic
colorectal cancer
EMEA license January 2005 March 2007 January 2008
NICE Not recommended
January 2007 Not assessed
SMC Not recommended
May 2006
Not recommended June
2007
Not recommended May
2006
AIFA Payment by performance MAA June 2008
IQWIG Not assessed
CT
(HTA& reimbursement)
ASMR II ASMR III
December 2007
ASMR IV
September 2008
Funded on top of the DRG without restriction on the drug’s indication June
2005
3P&R country tactics - MAJED ELHEWAIHI
AVASTIN

4. Indication
Non-Hodgkin’s lymphoma (NHL)
Chronic lymphocytic
leukaemia (CLL)
Rheumatoid arthritis
NICE First-line - in combination with a regimen of
cyclophosphamide, doxorubicin, vincristine
and prednisolone 2003
Relapse/refractory – as a monotherapy or in
combination with chemotherapy, is
recommended as an option for the induction
of
remission in people with relapsed stage III
or IV follicular non-Hodgkin’s lymphoma.
2008
First-line - in
combination with
fludarabine and
cyclophosphamide
2009
•Relapsed/refractory -in
combination with fludarabine
and cyclophosphamide 2010
•Inadequate
response/intolerant to
DMARD - in combination with
methotrexate 2010
SMC Previously untreated patients with stage III
to IV in combination with chemotherapy*
(2008)
Relapse/refractory - maintenance therapy*
(2006)
Relapse/refractory
(2010)
First-line + (2009)
Inadequate
response/intolerant to
DMARD- in combination with
methotrexate ++ 2006
Commission de
Transparence
Monotherapy - ASMR I 2006
In combination with
methotrexate – ASMR II
2006
4P&R country tactics - MAJED ELHEWAIHI
MABTHERA

5. Indication Sutent
MRCC
Nexavar
RCC
Sutent
GIST
Nexavar
HCC
EMEA license
CT (HTA&
reimbursement)
ASMR III (2nd line)
(2006)
ASMR II (1st line)
(2007)
ASMR II (2006) ASMR II (2007) ASMR IV (2008)
SMC SMC: not
recommended (1st or
2nd line) (2007)
SMC: not
recommended
(2006)
SMC: not recommended
initially; accepted with a PAS
(2009)
SMC: not
recommended
(2008)
NICE NICE: recommended
(with Patient Access
Scheme (PAS))
(2009)
NICE: not
recommended
(2009)
NICE: recommended (with
PAS) (2009)
NICE: not
recommended
currently in appeal)
(PAS scheme in
place) (2010)
UK
Sutent for 1st line treatment of advanced and/or mRCC was taken out of the multiple technology appraisal (MTA) process and
treated as a single technology appraisal (STA)
NICE recommended Sutent with a PAS. The first treatment cycle of Sutent is free to the National Health Service (NHS) and the
Department of Health (DoH) thought the PAS did not constitute an excessive administrative burden on the NHS
With the free first cycle, the cost per QALY was acceptable with an incremental cost-effectiveness ration (ICER) of £54,366 per
QALY for Sutent compared to IFN-a. The technology was then assessed against the end-of-life treatment criteria and was found to
meet the criteria with evidence considered sufficiently robust
5P&R country tactics - MAJED ELHEWAIHI
SUTENT