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Overall survival: 1st line therapy
2-year OS phase III studies mM
Bloomberg Business weekly 26 Feb 2015
Prices per month of oncology medicines
Presented By Veena Shankaran at 2016 ASCO Annual Meeting
Presented By Veena Shankaran at 2016 ASCO Annual Meeting
–
30 countries filled the survey35 oncology center included
Spain400
Belgium350
Poland1000
Belarus250
Russian Federation4000
Sweden500
Albania30
Slovenia150
30 countries, leading national melanoma centers
Switzerland: T-Vec registration and reimbursement
VEMURAFENIB DABRAFENIB VEMURAFENIB COBIMETINIB
DABRAFENIB TRAMETINIB
IPILIMUMAB PEMBROLIZUMAB NIVOLUMAB
Western Europe
Austria
Belgium ** **
Denmark
France
Germany
Greece ** **
Italy
Netherlands
Portugal ** ** ** ** ** ** **
Spain *** ***
Sweden
Switzerland **
UK
Eastern Europe
and South
Eastern Europe
Albania
Belarus
Bosnia and Herzegovina
Bulgaria
Croatia
Czech republic * * ** **
Estonia
Hungary ** ** ** ** **
Lithuania
Macedonia
Montenegro **
Poland * * ** **
Romania
Russia *** **** **** **
Serbia
Slovenia
Ukraine
Registered
Reimbursed
Not registered
Not reimbursed
*Reimbursed, but only for first-line treatment
**Reimbursed, but with large and time-consuming administrative work needed to obtain the medicine for the patient
***Reimbursed, but not fully available due to the hospital-restricted budget
****Reimbursed, but not available due to the drug shortage
Country Estimatedtotalnumber
ofmetastatic
melanomapatients
Estimated%ofpatients
treatedwithinnovative
medicines
Estimated%ofpatients
withoutaccessto
innovativemedicines
Estimatednumberof
patientswithoutaccess
toinnovativemedicines
WesternEurope
Austria 200 >90% 10%* /
Belgium 350 70-90% 10%* /
Denmark 350 >90% 10%* /
France 2000 >90% 10%* /
Germany 3000 >90% 10%* /
Greece NA 70-90% 10%* /
Italy 2000 70-90% 10%* /
Netherlands 800 70-90% 10%* /
Portugal 200 30-50% 50% 100
Spain 400 70-90% 10%* /
Sweden 100 50-70% 30%* /
Switzerland 350 70-90% 10%* /
UK 2000 10-30% 10%* /
TotalWE 11750 100
EasternandSouth-EasternEurope
Albania 30 10-30% 70% 21
Belarus 250 <10% 90% 225
BosniaandHerzegovina
60 <10% 90% 54
Bulgaria 150 30-50% 50% 75
Croatia 100 10-30% 70% 70
Czechrepublic 400 30-50% 50% 200
Estonia 50 50-70% 30% 15
Hungary 400 50-70% 30% 120
Lithuania 50 30-50% 50% 25
Macedonia 80 <10% 90% 72
Montenegro 30 10-30% 70% 21
Poland 1000 70-90% 10%* /
Romania NA 10-30% 70% NA
Russia 4000 <10% 90% 3600
Serbia 200 <10% 90% 180
Slovenia 150 >90% 10%* /
Ukraine 500 <10% 90% 450
TotalSEE 7450 5128
TotalWE+EE+SEE 19250 5228
• 19250 patients with metastatic melanoma in Europe• 7450 (39.7%) treated in Eastern and South-Eastern
Europe• 5128/7450 (69%) do not have the access to first-line
therapy recommended by the European guidelines(ESMO, EDF/EORTC/EADO).
• 5228/19250 (27%), i.e. almost third of all metastaticmelanoma patients do not have access to innovativemedicines.
*never in the first-line treatment
Serbia: vemurafenib reimbursed (without MEK inhibitor)pembrolizumab reimbursed for BRAF negative patients
Croatia: dabrafenib trametinib reimbursed pembrolizumab reimbursed
Romania: vemurafenib, dabrafenib trametinibnivolumab reimbursed
Estonia: nivolumab, pembrolizumab reimbursed BRAF+MEK inhibitor reimbursed
DELAY IN ACCESS THROUGH REIMBURSEMENT: 4-5 YEARS
Country nivo+ipi
Austria X
Belgium X
Bulgaria
Croatia
Cyprus
Czech Republic
Denmark X
Estonia
Finland X
France X
Germany X
Greece XHungary
Iceland
Ireland
Italy
Latvia
Lithuania
Luxembourg
Malta
Netherlands X
Norway
Poland
Portugal
Romania
Slovakia
SloveniaSpain X
Sweden X
Switzerland X
United Kingdom X
EMA registration: May 2016
Reimbursed in 32.4% countries
• Difficulties in implementing CU and EAP programmes:
– unharmonised legislative in some countries
– programmes are active only until the EMA registration, while reimbursementis in significant delay
• Insufficient number of clinical studies
– At least one clinical study for stage IV melanoma was available in 12/13 (92%) Western centers, and 6/17 (35%) from Eastern Europe centers in the surveyperiod.
• Clinically meaningful benefit of the treatment
• Acceptable toxicity profile
• Improvement of quality of life
17
18
19
MCBS v1.1
20
• Grading derived from the ESMO-MCBS provides a backbone for value evaluations for cancer medicines.
• ESMO-MCBS A+B for curative therapies and 4+5 for non-curative therapies should be highlighted for accelerated assessment of value and cost-effectiveness.
• While a high ESMO-MCBS score does not automatically imply high value (that depends on the price), the scale can be used to frame such considerations and can help public policymakers advance ‘ accountability for reasonableness’ in resource allocation deliberations
21
22
Presented By Elisabeth De Vries at 2017 ASCO Annual Meeting
1. ESMO in current and future guidelines
2. Doctors in everyday practice (patient care and teaching)
3. Academic groups
4. Industry
5. Organisations and countries using the scale as policy tool
23
Presented By Elisabeth De Vries at 2017 ASCO Annual Meeting
24
1. ESMO in current and future guidelines
2. Doctors in everyday practice (patient care and teaching)
3. Academic groups
4. Industry
5. Organisations and countries using the scale as policy tool
25
Presented By Elisabeth De Vries at 2017 ASCO Annual Meeting
VEMURAFENIB DABRAFENIB VEMURAFENIB COBIMETINIB
DABRAFENIB TRAMETINIB
IPILIMUMAB PEMBROLIZUMAB NIVOLUMAB
Western Europe
Austria
Belgium ** **
Denmark
France
Germany
Greece ** **
Italy
Netherlands
Portugal ** ** ** ** ** ** **
Spain *** ***
Sweden
Switzerland **
UK
Eastern Europe
and South
Eastern Europe
Albania
Belarus
Bosnia and Herzegovina
Bulgaria
Croatia
Czech republic * * ** **
Estonia
Hungary ** ** ** ** **
Lithuania
Macedonia
Montenegro **
Poland * * ** **
Romania
Russia *** **** **** **
Serbia
Slovenia
Ukraine
Registered
Reimbursed
Not registered
Not reimbursed
Switzerland: T-Vec registration and reimbursement
ESMO-MCBS could be used as a policy tool in HTA and reimbursement decisions at the national level?
29
30
Presented By Elisabeth De Vries at 2017 ASCO Annual Meeting
31
WHO Essential anti-
neoplastic medicines 2015
• Added: nilotinib and dasatinib for imatinib resistant CML
• Establishment of EML cancer medicines working group to coordinate comprehensive evaluation of cancer medicines for the EML
• Cooperation between ESMO and WHO: possible implementation of ESMO-MCBS in evaluation of medicines for the WHO essential list?
32
Non-curative setting: 1st line
33
Medication Trial nameFirst author
Early crossover
Primary outcome
PFScontrol(months)
PFS gain (months)
PFS HROS control(months)
OS gain(months)
OS HR
Increase in 2-year OS ≥10%
QoL ToxicityESMO MCBS v1.1 non-curative
DABRAFENIB TRAMETINIB COMBI-D
Long G 2015, 2017 no PFS 8.8 2.2 0.67 18.7 6.4 0.63 YES + 4
VEMURAFENIB COBIMETINIB
COBRIM Ascierto P 2016 no PFS 7.2 1 0.58 17.4 4.9 0.65 YES + 4
IPILIMUMAB Maio 2015 Maio 2015 yes OS 2.6 0.2 0.76 6.4 2.1 0.72 YES 4
NIVOLUMABCHECKMATE 066
Robert 2015 Atkinson SMR 2015 no OS 2.2 2.9 0.43 11.2 NR 0.43 YES + 4
PEMBROLIZUMABKEYNOTE-006
Robert 2015 Schachter ASCO 2016 yes OS 3.3 5 0.58 15.9 16.4 0.7 YES 4
NIVOLUMAB + IPILIMUMAB
CHECKMATE 067
Larkin 2015 Larkin AACR 2017 Scadendorf2017 no OS 4 4.6 0.42 NR NR ND ND same + 3
NIVOLUMAB + IPILIMUMAB PDL1
CHECKMATE 067Larkin 2015 Larkin AACR 2017
no OS 3.9 6.2 0.57 NR NR ND ND 4
Curative setting
34
Medication Trial name First authorEarly crossover
Primary outcome
PFScontrol(months)
PFS gain (months)
PFS HROS control(months)
OS gain(months)
OS HR
Increase in 2-year OS ≥10%
>5% imp. of survival at ≥3 year FU
QoL Toxicity
ESMO MCBS v1.1 curative
ESMO MCBS v1.1 non-curative
DABRAFENIB TRAMETINIB COMBI-D Long G 2015, 2017 no PFS 8.8 2.2 0.67 18.7 6.4 0.63 YES YES + A 4
VEMURAFENIB COBIMETINIB
COBRIM Ascierto P 2016
no PFS 7.2 1 0.58 17.4 4.9 0.65 YES NA + ND 4
IPILIMUMAB Maio 2015 Maio 2015yes OS 2.6 0.2 0.76 6.4 2.1 0.72 YES YES A 4
NIVOLUMAB CHECKMATE 066Robert 2015 Atkinson SMR 2015 no OS 2.2 2.9 0.43 11.2 NR 0.43 YES YES + A 4
PEMBROLIZUMABKEYNOTE-006
Robert 2015 Schachter ASCO 2016
yes OS 3.3 5 0.58 15.9 16.4 0.7 YES YES A 4
NIVOLUMAB + IPILIMUMAB
CHECKMATE 067Larkin 2015 Larkin AACR 2017
no OS 4 4.6 0.42 NR NR ND ND NA same + ND 3
NIVOLUMAB + IPILIMUMAB PDL1+
CHECKMATE 067Larkin 2015 Larkin AACR 2017
no OS 3.9 6.2 0.57 NR NR ND ND NA ND 4
Adjuvant interferon-alpha meta analysis Ives NJ et al. Eur J Cancer 2017; 82: 171-83.OS improvement 3% at 5 years (HR 0.9, CI 0.85-0.97), grade BSubgroup analysis: Ulcerated tumors OS improvement 10.5% at 10 years (HR 0.77, CI 0.64-0.92), grade A
Adjuvant ipilimumab, EORTC 18081OS improvement 11% at 5 years (HR 0.72), grade ASubstantial toxicity, QoL not deteriorated, downgrade to B?
ESMO 2017: Dabrafenib+trametinib ?Vemurafenib ?Pembrolizumab ? 35
36
0
10
20
30
40
50
60
70
80
90
100
Vemurafenib Dabrafenib Vemurafenibcobimetinib
Dabrafenibtrametinib
Ipilimumab Pembrolizumab Nivolumab Nivolumabipilimumab
(%)
registration reimbursement
ESMO MCBS 4 4 4 (5) 4 (5) 4 4 (5) 4 (5) 3 (4)
Perc
enta
ge o
f co
un
trie
s
o EU Directive – recommendation that registered medicine should be available on the market in 120 days, but delays are common
o EU Network for Health Technology Assessment: o Harmonization of cost-effectiveness analysis until 2020o Parallel submissions to EMA and EU HTA proposedo Common EU price?o ESMO-MCBS as a tool for centralized prioritization?
o Harmonization of reimbursement process?o Added value reimbursement prioritization based on the central
assessment of added value for each medicine OR assessment of added value at the national level
Pricing?
National reimbursement listing determinants of new cancer drugs: a retrospective analysis of 58 cancer treatment appraisals in 2007–2016 in South Korea. Kim ES, et al. Expert Rev Pharmacoecon Outcomes Res. 2017 Jan 3:1-9.
• Three variables increased the likelihood of reimbursement listing:• clinical improvement, • below alternative’s price, • risk-sharing arrangement.
• Cancer drug’s listing increased from 17% to 47% after risk-sharing agreement implementation.
• Take an active role through involvement in professional oncological organizations to start and maintain a dialogue with:
– European and national policy makers
– Patients’ organizations
– Pharmaceutical industry
• to improve the access to innovative medicines for their patients.
• Education of practicing oncologists is necessary to ensure basic understanding of the process of drug approval and reimbursement in order to be able to actively participate in the process.
43
• A dynamic tool with planned revisions and updates based on careful and transparent revision process
• Commitment to “accountability for reasonableness”
• Could serve as useful tool for establishing a fair process for priority setting in public policy
• Further adjustments: patient reported outcomes
44
Thank you for your attention!
EU Policy Committee, Global Policy Committee
Working Group for the access to medicines
Task Force for innovation in skin cancer care