Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
0© phamax AG, 2017- All Rights Reserved
Confidential
Improving the Access to Immuno-Oncology in Europe: Barriers and Potential Solutions
Date: 31st Jan., 2017
1© phamax AG, 2017- All Rights Reserved
Executive summary
2© phamax AG, 2017- All Rights Reserved
Oncologists from
17EU countries
responded to
the survey
89% believed
I-O therapies
are
very important
<50% oncologists were highly
familiar with I-O and
hence only <45% prescribed them
~78% oncologists
positive about
role of combination
I-O therapies
Flexible reimbursement guidelines or cost-effectiveness decision parameters (83%) Less stringent regulatory review process (56%) Defining target population (44.4%) Clinical practice guidelines (38.9%) Training HCPs (27.8%)
Solutions
suggested to
improve access to
I-O therapies
2
>77% encountered
challenges in
prescribing
I-O therapies
83%faced challenges in
selecting
the right patient
population
100% support
early access
programs
for I-O
~39% strongly believed that
uniformity and
stratification of HTA will
improve access
3© phamax AG, 2017- All Rights Reserved
Background
4© phamax AG, 2017- All Rights Reserved4
Cancer is a major healthcare concern in Europe demanding advanced treatment strategies
2.45 million 1.23 million 126 billion 75 billion
New cancercases
per year1
Deaths per year1
Euros in
total cost1
Eurosin
indirect cost1
5© phamax AG, 2017- All Rights Reserved5
Growing trend of the global I-O market
• I-O therapies are gaining a strong
foothold in the cancer treatment paradigm
over conventional cancer treatment due to
the following advantages3,4:
− Active immunity
− Sustained response
− Applicability in multiple indications
− Favorable adverse effect profile
• 78% of the new oncology medicines launched
between 2010 and 2014 were available within
the greater EU by 20155
Expected rise in the global I-O market (USD billion)2
34
14
1.4
2014 2019 2024
6© phamax AG, 2017- All Rights Reserved6
The I-O arena is expecting several drug approvals, even for second and third indications
2015: Pembrolizumab for melanoma8
2015:Nivolumab
for melanoma and NSCLC7
Atezolizumab (Approved by FDA
in March 2016, Under review by
EMA)9
2016:Nivolumab
for RCC (Extended approval)7
Ipilimumab for melanoma6
Phase IPhase IIPhase III
Registered Under investigation
Avelumab9
Tremelimumab9
Pidilizumab9
Durvalumab9
7© phamax AG, 2017- All Rights Reserved
The survey objectives
7
Survey objectives
• Limited and disproportionate access to I-O therapies across Europe despite demonstrated efficacy and safety in clinical trials5,10
• A survey was conducted to explore the status of I-O therapies in European countries to understand the key hurdles that limit access and to develop solutions to overcome the same
Assess the clinical practice patterns of oncologists in prescribing or recommending I-O therapies
Understand the barriers faced by oncologists in using I-O therapies
To assess the oncologists’ awareness on the status of I-O therapies in the European countries
Encourage oncologists to propose solutions and recommendations to improve access to I-O therapies in Europe
Assess the causes of disparities in accessing cancer therapy across Europe
8© phamax AG, 2017- All Rights Reserved
Methodology
9© phamax AG, 2017- All Rights Reserved
• Both quantitative and qualitative data were collected
• Individual responses and cumulative analysis reports were
generated in Microsoft Excel
4Data collection
• Extensive literature search in databases such as MedLINE,
Google Scholar and various regulatory, government, and
healthcare websites to identify key topics
• Questionnaire consisted of three sections and 13 questions
overall
1Questionnaire
• Oncologists across the EU: Oncology practitioners involved in
policy shaping activities or associated with leading oncology
societies
• Dendron11 – A scientific platform by focus scientific research
center (FSRC) where stakeholders from different fields interact,
portray their activities, share knowledge and best practices
• Survey sent to 206 oncologists
2Participants
• Emails and LinkedIn
• Questionnaire was made available on a website
(www.esurveyspro.com)
• Duration: three weeks between May – June 2016
3Communication and survey platform
9
Methodology
10© phamax AG, 2017- All Rights Reserved
Results
11© phamax AG, 2017- All Rights Reserved
• Inequities in cancer care has led to more demands from the EEC10,13
• Only 1/3rd of the former Eastern Bloc countries have access to at least one of the new
targeted I-O5
• The Czech Republic launched a mass cancer screening program focused on the increased demand
of drugs due to the increased burden of cancer14
• Response rate: 9%
• 18 participants from Albania (AL), Austria (AT), Bosnia and
Herzegovina (BA), Croatia (HR), Czech Republic (CZ), Denmark (DK),
Italy (IT), Lithuania (LT), Poland (PL), Kosovo (RS), Portugal (PT),
Romania (RO), Slovak Republic (SK), Slovenia (SI), Switzerland
(CH), Ukraine (UA), and United Kingdom (UK)
• Most responses (66.7%) were from the emerging European
countries (EEC)12
• Most oncologists have a clinical experience of >5years and are
associated with various universities across Europe
Findings from the survey
Evidence from secondary research
11
Survey results
Developed European Countries
Emerging European Countries
12© phamax AG, 2017- All Rights Reserved
PART 1: Experience with I-O therapies
The questions in this part were mainly on the basic scientific knowledge on the mechanism of action of I-O therapies, recent developments in this space, clinical experience with I-O therapies and challenges with I-O access
13© phamax AG, 2017- All Rights Reserved
• There was a lag between the advancing I-O field and knowledge among
oncologists in the EU-5 and Greece in a survey15,16
− Only 35% oncologists from Europe interviewed in a survey were
well-informed on I-O
− There was a disparity in knowledge on I-O, irrespective of economic and
scientific development, policy making, education and general population health
• As per another survey, 76% of oncologists wanted to be trained or educated on cancer
immunotherapy4
• Overall, 44% of the oncologists were highly familiar
• All oncologists in the DEC were moderate to extremely familiar
• In the EEC, 33% oncologists were only slightly familiar
Findings from the survey
Evidence from secondary research
13
Q1. How familiar are you with the concept of I-O therapies?
33.3%
66.6%
50.0%
16.6%
33.3%
Extremely familiar
Moderately familiar
Slighty familiar
Figure 3: Knowledge about I-O
Developed European Countries
Emerging European Countries
14© phamax AG, 2017- All Rights Reserved
• The overall attitude towards I-O therapies was largely positive amongst various
HCPs17
− Oncologists: 48% positive
− Surgeons: 65% positive
− Nurses: 77% positive
• The overall optimism in I-O therapies is also shown by the number of new therapies getting
approved3,6,7,8
− Three I-O therapies currently approved in Europe: Ipilimumab (2011) for advanced melanoma,
Nivolumab (2015) for advanced melanoma, NSCLC, Pembrolizumab (2015) for advanced melanoma
and seeking expanded approvals
89% believe I-O is very important
Findings from the survey
Evidence from secondary research
14
Q2.Compared to other oncology therapy measures (chemotherapy, radiation therapy, and surgery), what is the importance of I-O therapies in improving the outcomes of patients with cancer?
Immuno-modulatory
mAbs
Activation or stimulation of
receptors expressed on the
surface of immune effector cells like tumor necrosis
factor
Inhibitors of cytotoxic T
lymphocyte-associated protein
4 (CTLA-4) receptors or their
ligands
Inhibitors of programmed cell
death 1 (PD-1) receptors or their
ligands
Actagainst factors
released in the tumor environment that
diminish the immune system ability, (e.g.
transforming growth factor β1)
15© phamax AG, 2017- All Rights Reserved
• Common barriers in recommending/prescribing cancer immuno-therapies:
cost and reimbursement issues (58%), past failures in clinical trials (45%), access/
formulary restrictions (44%) and lack of long-term safety/efficacy data (40%)4,10,16-23,
• The Institute for Clinical Immuno-Oncology (ICLIO) educates clinicians and patients
about the clinical implications and benefits of I-O in day to day practice24
• The ESMO has developed clinical practice guidelines to facilitate the adaptation of I-O in
clinical practice25
Positive trend towards recommendation of I-O therapies,
however, not many prescribe them in clinical practice
Findings from the survey
Evidence from secondary research
15
Q3. Please indicate your clinical experience in recommending and/or prescribing following classes of I-O therapies
44.4% 44.4%
16.7%
38.9%44.4%
16.7%22.2%
50.0%
27.8%
Recommended andPrescribed
Recommended but did notprescribe
Neither recommended norprescribed
Clinical experience with I-O therapies
PD-1/PD-L1 inhibitors (nivolumab and pembrolizumab)
CTLA-4 inhibitors (lpilimumab)
Combination of PD-1 inhibitor and CTLA-4 inhibitor
16© phamax AG, 2017- All Rights Reserved
• Increased familiarity with I-O therapies does not necessarily increase prescribing
− Nearly 68% of oncologists in a survey showed interest in immunotherapy;
however, only 24% had direct experience with them4
• Practice gaps might be due to the availability of I-O therapies in the country and
understanding the attributes of I-O therapies (e.g. mechanism of action, clinical efficacy and
treatment response)26
• Out of the 14 oncologists extremely or moderately familiar with
I-O therapies:
− 8 prescribed PD1/PD-L1 inhibitors (4 in DEC and 4 in EEC)
− 7 prescribed CTLA-4 inhibitors (4 in DEC and 3 in EEC)
− Only 4 prescribed combination therapies (2 in DEC and 2 in EEC)
Findings from the survey
Evidence from secondary research
16
Q3. Please indicate your clinical experience in recommending and/or prescribing following classes of I-O therapies
28%
36%
36%
50%
36%
14%
57%36%
7%
Recommended and prescribed
Recommended but did not prescribe
Neither Recommended nor prescribed
A) Experience with PD1/PD-L1 inhibitors B) Experience with CTLA-4 inhibitors
C) Experience with combination I-O
17© phamax AG, 2017- All Rights Reserved
• Varied clinical response in trials depending on the status of the biomarker
(E.g. No clear survival benefit for pembrolizumab in the subset of patients with
EGFR mutation even in the presence of higher proportion score for PD-L127,28
• Although efficacious, these drugs are not affordable to all patients
− >50 HTA agencies exist in Europe, leading to unequal evaluation criteria and disparity in
reimbursement decisions23,29
• Oncologists need to be more aware on AEs for checkpoint inhibitors which have distinct side effects
compared to conventional chemotherapy and may occur at different time intervals30
• Conventional methods to determine MTD in clinical trials have failed to determine appropriate dosagef or I-O
drugs mandating the development of novel methods to determine the effective doses31,32
• Delayed response or pseudoprogression are specific attributes of I-O therapies that limit compliance33,34
• All oncologists from DEC and about 66% from the EEC faced
challenges
• The top three challenges were: Selecting the right patient
population (83.3%), Cost/reimbursement of the drug (50%), AE profile
of the drug (44.4%)
Findings from the survey
Evidence from secondary research
17
Q4. Have you experienced any barriers in recommending/prescribing I-O therapies to your patients?Q5. Please assign ranking based on the challenges that you face while recommending/prescribing I-O therapies to your patients?
77.8%
22.2%
Yes
No
Faced any challenges?
22.2%22.2%
44.4%50.0%
83.3%
Challenges with I-O therapies
Delayed response
Dosing or duration of treatment
Side-effect profile
Cost/Reimbursement
Target patient population
18© phamax AG, 2017- All Rights Reserved
• Combination therapy of nivolumab + ipilimumab showed tumor reduction of
80%, and more among 53% patients with advanced melanoma35
• AEs related to combination therapy were similar in experience with monotherapy and
were reversible35
• Various I-O combinations are being investigated
− mAbs + small molecules
− mAbs + vaccines
− I-O + radiotherapy/other chemotherapy36
• Complications of combination therapy: Cumulative toxicities, extensive collaboration between pharma companies for
development and research and difficult regulatory review37,38
~78% oncologists were positive that combination therapy could
perhaps improve outcome and prolong patients’ lives
Findings from the survey
Evidence from secondary research
18
Q6. What do you think will be the role of combination therapy (i.e. combining two or more I-O products with different mechanisms of action?
22.2%
77.8%
Some what improve outcomeand prolong patients' lives
Will improve outcomes andprolong patients' lives
significantly
Role of combination therapy
19© phamax AG, 2017- All Rights Reserved
PART 2: Status of I-O therapies in respondent’s country
This part included questions on the status of reimbursement of I-O therapies in
the respective countries and the role of the various government and public
organizations and the pharmaceutical industry in controlling the access to I-O
20© phamax AG, 2017- All Rights Reserved
• Disparities in pricing and reimbursement decisions for oncology drugs across
the EU member states is widely known10
− Till 2015, while >25 innovative cancer drugs were covered under
reimbursement in Netherlands, Italy and Switzerland; the EEC such as Czech Republic
and Poland reimbursed <5 of these drugs39
− One example is Jakavi (ruxolitinib), which is reimbursed in the northern and central European
countries but not in the eastern European countries40
• Reimbursement status of I-O therapies:
− Not reimbursed in 6 countries in EEC: Romania, Slovak Republic,
Albania, Ukraine, Kosovo and Bosnia and Herzegovina
− Not reimbursed in 1 country in DEC: Portugal
− Not available in Lithuania
− Reimbursed completely or partially in DEC
Findings from the survey
Evidence from secondary research
20
Q7. What is the reimbursement status of I-O therapies in your country?
Reimbursement status of I-O therapies
8.3%
50.0%
25.0%
16.6% 16.6%
33.3%
50.0%
I-O therapies notavailable in the
country
Not reimbursedPartially reimbursedCompletelyreimbursed
Developed European Countries
Emerging European Countries
21© phamax AG, 2017- All Rights Reserved21
Q8. Who plays a major role in improving access of oncology drugs in your country?
Partnership between WHO and European Society for Medical Oncology (ESMO) since 2002 driving efforts from all sectors to improve cancer care 47
BMS launched compassionate use program for Nivolumab in Ireland. It benefits 200 patients with advanced lung cancer and is free for these patients for 30 days 45,46
NICE reviews all new cancer drugs and changes in indications for existing drugs in the UK NICE negotiated with BMS to reduce the pricing for Ipilimumab 43,44
The ESMO Patient Advocates Working Group (PAWG) and Lung Cancer Europe educates HCPs and improves access 41,42
Payers
(33.3%)
Advocacy groups
(11.1%)
Examples of initiatives by variousauthorities/organizations
Organizations and bodiesinfluencing access
Pharmaceutical companies
(38.8%)
Government
(77.7%)
22© phamax AG, 2017- All Rights Reserved
Part 3: Future recommendations to improve access to I-O therapies
This part included questions on suggestions from experts to improve access to I-O
23© phamax AG, 2017- All Rights Reserved
• Flexible reimbursement, funds and risk sharing agreements decrease cost burden19,48-50
− Special innovation funds in Italy, CDF in UK for research and development− Ipilimumab was approved by NICE following price discounts by BMS
• Identification of target population can be easier with predictive biomarkers and companion diagnostics− Pembrolizumab was approved with companion diagnostics to determine responders
based on PD-1 expression20,21,28
• Revisions in clinical trial methods will generate credible evidence and ease the adaptation of these drugs in clinical practice− Determine biologically efficacious doses instead of MTD51
− Assess response through irRC52
• Many organizations are continuously working to educate HCPs− CIC and CIMT are working towards educating and improving clarity on I-O15
− The ECPC has also developed a framework on awareness to improve access53
Most important suggestions were the improvisation in
reimbursement guidelines or cost-effectiveness decision
parameters (83%) followed by less stringent regulatory review
process (56%) and defining target population (44.4%)
Findings from the survey
Evidence from secondary research
23
Q9. In your country, what could be done to improve access toI-O therapies?
Methods to improve access
27.8%27.8%
38.9%44.4%
55.6%
83.3%
Preclinical and clinical
evidence
TrainingHCPs
Clinical practice
guidelines
Defining target
population
Flexible regulatory
review
Flexible reimbursement
24© phamax AG, 2017- All Rights Reserved
• More than 50 HTA agencies exist in Europe leading to inconsistencies in the evaluation criteria and disparity in access to oncology drugs23
− Differences in reimbursement decisions (from 2002-2004) on cancer drugs in Europe: England rejected reimbursement in 21.52% cases, Sweden and France rejected only 3-4%. Germany had 1% non-favorable opinions and Spain and Netherlands had none39
− Trastuzumab (Herceptin) is available widely in many countries, but it requires29
preapproval or is available to patients at out-of-pocket costs in some European countries − NICE rejected reimbursement of Imbruvica (ibrutinib) contradictory to the decision by other EU
countries such as Greece54
• Personalizing reimbursement schemes and developing precision medicines catering to a group of responders could be advantageous. E.g. Herceptin treatment coverage in UK applied only to patients showing higher degree of HER2 staining and responding better19
Seven out of the 18 (~39%) strongly believed that uniformity in
the HTA process across Europe and its further stratification will
improve access
Findings from the survey
Evidence from secondary research
24
Q10. Do you believe that uniformity in Health Technology Assessment (HTA) model across European region and stratification of HTA (e.g. based on those who respond compared to those who do not) will help improve the access to I-O therapies across European region?
Will uniformity and stratification of HTA improve access to I-O?
38.9%
61.1%
Strongly believe
Somewhat believe
25© phamax AG, 2017- All Rights Reserved
• Early access or compassionate use programs have improved access in
Europe55
• Nivolumab was approved on compassionate grounds in Ireland. This program
benefits 200 patients who get it free for 30 days44,56
• Compassionate access programs for oncology drugs existing in Austria, Estonia, Greece,
Hungary, Italy, Lithuania, Portugal, and Spain etc. have shown positive outcomes45
All the oncologists supported early access programs for
I-O therapies
Findings from the survey
Evidence from secondary research
25
Q11. Should early access be provided to new I-O therapies?
Opinion on early access provision for new I-O therapies
100%
Yes
26© phamax AG, 2017- All Rights Reserved
Findings from survey Evidence from secondary research
26
Q12. In your view, what efforts could be taken by the following stakeholders to improve the access to I-O therapies in your country?
• Improved reimbursement guidelines, negotiated prices of these
drugs and improved research funding are a priority for many
researchers19,48-50
• Literature suggests the lack of education and awareness on I-O.
More training and education programs should be conducted as
per HCPs4,15,16
• Developing guidelines and recommendations for target
populations, dose regimen, clinical evaluation and managing
side-effects in addition to appropriate dissemination of clinical
trial data will help better clinical adaptation20,21,30,51,52
• Early access programs and fast tracking the review process will
bring these drugs sooner to the market44,45,55,56
• Strategic planning like the framework developed by the ECPC
will help in healthcare reforms and suitable actions53
27© phamax AG, 2017- All Rights Reserved
High cost and lagging reimbursement standards are the most common barriers hindering the patient access to these drugs
27
Q13. Share your experience with I-O therapies
Oncologists believe that these drugs will help reduce the burden of cancer
More funding and development of biomarkers will facilitate access
Some of the oncologists in the EEC only experienced the drugs in clinical trial settings
28© phamax AG, 2017- All Rights Reserved
Conclusion
29© phamax AG, 2017- All Rights Reserved29
Strengths and Limitations of the survey
LimitationsStrengths
• Responses from oncologists from 17 of the 28 EU
countries with varied economical and development
status
• Five or more years of clinical experience of
the participating oncologist, indicating their expertise
• Collection of qualitative responses - suggestions and
recommendations
• Response rate of ~10%
• Only one response from each country (except Poland)
• Results not analysed to assess the statistical significance
30© phamax AG, 2017- All Rights Reserved
Conclusion
31© phamax AG, 2017- All Rights Reserved31
Conclusion
Reasons cited by oncologists:• High price • Lack of awareness and education about the target population, dose, duration, efficacy, and safety profiles of these drug • Disparities across Europe delaying the uniform use in clinical practice
Despite the survey respondents believing that I-O may transform the standard of care in oncology, not many of them had used these therapies in clinical practice
Solutions suggested by the oncologists: • Education, awareness and appropriate dissemination of clinical trial data • Clear treatment policies • Improvisation in reimbursement guidelines
The gaps should be addressed by reducing the economic and disease burden across the various member states in Europe
32© phamax AG, 2017- All Rights Reserved32
References
1. Insights on Immuno-Oncology Drug Development and the Field’s True Potential Biopharm insight [http://www.biopharminsight.com/articles/insights-immuno-oncology-drug-development-and-field-s-true-potential]. Date accessed: 22 Jun 2016
2. The Immuno-oncology market. Key players, leading contenders, and the next generation [https://www.dcat.org/Public/Pdfs/DCATWeek16/PIO/Rachel%20Webster%20FINAL%203.11.160-OK-Distrib.pdf]. Date accessed: 22 Jun 2016
3. Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buqué A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, Apte RN, Aranda F, Ayyoub M, Beckhove P, Blay JY, Bracci L, Caignard A, Castelli C, Cavallo F, Celis E, Cerundolo V, Clayton A, Colombo MP, Coussens L, Dhodapkar MV, Eggermont AM, Fearon DT, Fridman WH, Fučíková J, Gabrilovich DI, Galon J, Garg A, Ghiringhelli F, Giaccone G, Gilboa E, Gnjatic S, Hoos A, Hosmalin A, Jäger D, Kalinski P, Kärre K, Kepp O, Kiessling R, Kirkwood JM, Klein E, Knuth A, Lewis CE, Liblau R, Lotze MT, Lugli E, Mach JP, Mattei F, Mavilio D, Melero I, Melief CJ, Mittendorf EA, Moretta L, Odunsi A, Okada H, Palucka AK, Peter ME, Pienta KJ, Porgador A, Prendergast GC, Rabinovich GA, Restifo NP, Rizvi N, Sautès-Fridman C, Schreiber H, Seliger B, Shiku H, Silva-Santos B, Smyth MJ, Speiser DE, Spisek R, Srivastava PK, Talmadge JE, Tartour E, Van Der Burg SH, Van Den Eynde BJ, Vile R, Wagner H, Weber JS, Whiteside TL, Wolchok JD, Zitvogel L, Zou W and Kroemer G (2014) Classification of current anticancer immunotherapies. Oncotarget 5(24):12472-508
4. Mellstedt H, Gaudernack G, Gerritsen WR, Huber C, Melero I, Parmiani G, Scholl S, Thatcher N, Wagstaff J, Zielinski C (2014) Awareness and understanding of cancer immunotherapy in Europe. Hum Vaccin Immunother10(7):1828-35
5. Global Oncology Trend Report. A Review of 2015 and Outlook to 2020 [https://morningconsult.com/wp-content/uploads/2016/06/IMS-Institute-Global-Oncology-Report-05.31.16.pdf]. Date accessed: 22 Jun 20166. Yervoy Ipilimumab [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002213/human_med_001465.jsp&mid=WC0b01ac058001d124]. Date accessed: 22 Jun 20167. Opdivo Nivolumab [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003985/human_med_001876.jsp&mid=WC0b01ac058001d124]. Date accessed: 22 Jun 20168. Keytruda Pembrolizumab [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003820/human_med_001886.jsp&mid=WC0b01ac058001d124]. Date accessed: 22 Jun 20169. Insights on Immuno-Oncology Drug Development and the Field’s True Potential Biopharm insight [http://www.biopharminsight.com/articles/insights-immuno-oncology-drug-development-and-field-s-true-potential].
Date accessed: 22 Jun 201610. Lawler M, Apostolidis K, Banks I, Florindi F, Militaru M, Price R, Sullivan R and De Lorenzo F Challenging the europe of disparities in cancer. A framework for improved survival and better quality of life for european
cancer patients. European Cancer Patient Coalition– ECPC [http://www.ecpc.org/Documents/Policy&Advocacy/Europe%20of%20Disparities/Europe%20of%20Disparities%2027th%20Sept%202015.pdf]. Date accessed: 22 Jun 2016
11. Dendron A scientific platform [http://www.fs-researchcenter.com/dendron.aspx] Date accessed: 22 Jun 201612. Emerging Europe Monitor [http://www.emergingeuropemonitor.com/] Date accessed: 22 Jun 201613. Helwick C Access to Cancer Medicines Not Uniform Across Europe The Asco Post [http://www.ascopost.com/issues/september-10-2015/access-to-cancer-medicines-not-uniform-across-europe/]. Date accessed: 22 Jun
201614. Cancer Screening Initiatives Boost Demand For Oncology Drugs [http://www.bmiresearch.com/news-and-views/cancer-screening-initiatives-boost-demand-for-oncology-drugs]. Date accessed: 22 Jun 201615. Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E, Bramson JL, Britten CM, Cao X, Carson WE, Chang AE, Characiejus D,
Choudhury AR, Coukos G, de Gruijl T, Dillman RO, Dolstra H, Dranoff G, Durrant LG, Finke JH, Galon J, Gollob JA, Gouttefangeas C, Grizzi F, Guida M, Håkansson L, Hege K, Herberman RB, Hodi FS, Hoos A, Huber C, HwuP, Imai K, Jaffee EM, Janetzki S, June CH, Kalinski P, Kaufman HL, Kawakami K, Kawakami Y, Keilholtz U, Khleif SN, Kiessling R, Kotlan B, Kroemer G, Lapointe R, Levitsky HI, Lotze MT, Maccalli C, Maio M, Marschner JP, Mastrangelo MJ, Masucci G, Melero I, Melief C, Murphy WJ, Nelson B, Nicolini A, Nishimura MI, Odunsi K, Ohashi PS, O'Donnell-Tormey J, Old LJ, Ottensmeier C, Papamichail M, Parmiani G, Pawelec G, Proietti E, Qin S, Rees R, Ribas A, Ridolfi R, Ritter G, Rivoltini L, Romero PJ, Salem ML, Scheper RJ, Seliger B, Sharma P, Shiku H, Singh-Jasuja H, Song W, Straten PT, Tahara H, Tian Z, van Der Burg SH, von Hoegen P, Wang E, Welters MJ, Winter H, Withington T, Wolchok JD, Xiao W, Zitvogel L, Zwierzina H, Marincola FM, Gajewski TF, Wigginton JM and Disis ML (2011) Defining the critical hurdles in cancer immunotherapy. J Transl Med 9:214
33© phamax AG, 2017- All Rights Reserved33
References (continued)
16. Borrello IM, Schaffer MM, Roehrl E and Marshall JF (2014) Identification of differences in immunotherapy knowledge and practice patterns among oncologists from six European countries. Mol Clin Oncol 2(2):269-27417. Current and future challenges of innovative oncology drug development ecancernews [http://ecancer.org/news/7158-current-and-future-challenges-of-innovative-oncology-drug-development.php]. Date accessed: 22
Jun 201618. Anti-Cancer Medicines Availability Study [http://www.esmo.org/Policy/Anti-Cancer-Medicines-Availability]. Date accessed: 22 Jun 201619. Henry C and Wagner R (2013) ASCO analysis: market access challenges in Europe for PD-1/PD-L1 targeted therapies in oncology Pharmaphorum [http://www.kantarhealth.com/docs/press-articles/asco-analysis---
market-access-challenges-in-europe-for-pd-1-pd-l1-targeted-therapies-in-oncology.pdf?sfvrsn=4]. Date accessed: 22 Jun 201620. Hoos A, Britten CM, Huber C and O'Donnell-Tormey J (2011) A methodological framework to enhance the clinical success of cancer immunotherapy Nat Biotechnol 29(10):867-70 21. Hoos A and Britten C (2012) The immuno-oncology framework: Enabling a new era of cancer therapy. Oncoimmunology 1(3):334-33922. Kudrin A (2012) Reimbursement challenges with cancer immunotherapeutics Hum Vaccin Immunother 8(9):1326-3423. Bergmann L, Enzmann H, Broich K, Hebborn A, Marsoni S, Goh L, Smyth JF and Zwierzina H (2014) Actual developments in European regulatory and health technology assessment of new cancer drugs: what does this
mean for oncology in Europe? Ann Oncol 25(2):303-624. ACCC Launches First Immuno-Oncology Program for Community-Based Cancer Care [http://immuno-oncologynews.com/2015/07/08/accc-launches-first-immuno-oncology-program-for-community-based-cancer-care/].
Date accessed: 22 Jun 201622 Jun 201625. ESMO Clinical Practice Guidelines [http://www.esmo.org/Guidelines]. Date accessed: 22 Jun 201622 Jun 201626. Herrmann T and Warren C (2014) Current clinical challenges and opportunities in oncologists' familiarity and understanding of immuno-oncology. J Immunother Cancer 2(Suppl 3): P18027. Medina PJ and Adams VR (2016) PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses. Pharmacotherapy 36(3):317-3428. Shu CA and Rizvi NA (2016) Into the Clinic With Nivolumab and Pembrolizumab. Oncologist 21(5):527-829. Towards a Harmonised EU Assessment of the Added Therapeutic Value of Medicines [http://www.europarl.europa.eu/RegData/etudes/STUD/2015/542219/IPOL_STU(2015)542219_EN.pdf]. Date accessed: 22 Jun
201630. Managing the Side Effects of Novel Cancer Immunotherapeutics. Recognising and controlling the adverse effects of CTLA-4 and PD-1 blocking agents [http://www.esmo.org/Oncology-News/Managing-the-Side-Effects-
of-Novel-Cancer-Immunotherapeutics]. Date accessed: 22 Jun 201631. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders
RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM and Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N EnglJ Med 366(26):2443-54
32. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, Drengler R, Chen C, Smith L, Espino G, Gergich K, Delgado L, Daud A, Lindia JA, Li XN, Pierce RH, Yearley JH, Wu D, Laterza O, Lehnert M, Iannone R and Tolcher AW (2015) Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Clin Cancer Res 21(19):4286-93
33. Hodi FS, Hwu WJ, Kefford R, Weber JS, Daud A, Hamid O, Patnaik A, Ribas A, Robert C, Gangadhar TC, Joshua AM, Hersey P, Dronca R, Joseph R, Hille D, Xue D, Li XN, Kang SP, Ebbinghaus S, Perrone A and Wolchok JD (2016) Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab. J Clin Oncol 34(13):1510-7
34. Chiou VL, Burotto M (2015) Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol 33(31):3541-335. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak
CE, Hong Q, Korman AJ, Wigginton JM, Gupta A and Sznol M (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–33
34© phamax AG, 2017- All Rights Reserved34
References (continued)
31. Formenti SC and Demaria S (2013) Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 105(4):256-65 32. Drake CG (2012) Combination immunotherapy approaches. Ann Oncol 23 Suppl 8:viii41-6 33. Talreja C, Prusty S, Jago C and Kibble A Immuno-oncology combinations: a Thomson Reuters report. Drugs of the Future 39(11):793-79834. Pujolrasa LM, Cairnsa J (2015) Why do some countries approve a cancer drug and others don’t? Journal of Cancer Policy 4:21–2535. Access to innovative cancer drugs in Poland in comparison with selected European Union countries and Switzerland , 2015. Report ordered by Young People Oncology Foundation Alivia and prepared by EY Poland
[https://www.alivia.org.pl/raport2015/05_05_2015_Raport_wersja_EN.pdf] Date accessed: 22 Jun 201636. ESMO Patient Advocates Working Group [http://www.esmo.org/About-Us/Who-We-Are/EU-Policy-Committee/Patient-Advocates-Working-Group]. Date accessed: 22 Jun 201637. Lung Cancer Europe [http://www.lungcancereurope.eu/]. Date accessed: 22 Jun 201638. Big Changes to Cancer Drugs Fund as NICE Takes Over All UK Oncology Evaluations [http://www.contextmatters.com/blognews/2016/5/5/big-changes-to-cancer-drugs-fund-as-nice-to-take-over-all-uk-oncology-
evaluation]. Date accessed: 22 Jun 201639. NICE issues guidance recommending two new cancer treatments [ https://www.nice.org.uk/news/press-and-media/nice-issues-guidance-recommending-two-new-cancer-treatments]. Date accessed: 22 Jun 201640. New cancer drug to be given to patients free for 30 days [http://www.irishtimes.com/news/health/new-cancer-drug-to-be-given-to-patients-free-for-30-days-1.2668501]. Date accessed: 22 Jun 201641. Expanded Access Program (Compassionate Use) Investigator Requests [http://www.bms.com/clinical_trials/investigator_sponsored_research/Pages/expanded-access-program.aspx]. Date accessed: 22 Jun 201642. Ullrich A, Ciardiello F, Bricalli G, Cherny NI and Eniu A (2016) ESMO and WHO: 14 years of working in partnership oncancer control. ESMO Open 1:e000012 doi:10.1136/esmoopen-2015-00001243. Patient Access to Immuno-Oncology Agents—A US Policy Perspective [http://www.ajmc.com/journals/evidence-based-oncology/2016/february-2016/patient-access-to-immuno-oncology-agents-a-us-policy-
perspective/P-2#sthash.8Zc1BPNm.dpuf]. Date accessed: 22 Jun 201644. McDougall JA, Ramsey SD and Shih YT (2014) Financial Toxicity: A Growing Concern Among Cancer Patients in the United States. ISPOR CONNECTIONS 20(2):10-11 45. Adamski J, Godman B, Ofierska-Sujkowska G, Osińska B, Herholz H, Wendykowska K, Laius O, Jan S, Sermet C, Zara C, Kalaba M, Gustafsson R, Garuolienè K, Haycox A, Garattini S and Gustafsson LL (2010) Risk sharing
arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv Res 10:15346. Report from Dose Finding Workshop European Medicines Agency, London, 04 – 05 December 2014 7 April 2015 EMA/117491/2015
[http://www.ema.europa.eu/docs/en_GB/document_library/Report/2015/04/WC500185864.pdf]. Date accessed: 22 Jun 201647. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R and Hodi FS (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-
related response criteria. Clin Cancer Res 15(23):7412-2048. Immuno-oncology: a policy action framework Creating enabling policies to provide patients with an innovative cancer treatment modality [http://www.ecpc.org/Documents/Policy&Advocacy/Immuno-
Oncology/Event%2019th%20Nov%202014/IO%20action%20framework%20FINAL%20Dec14%20lores.pdf]. Date accessed: 22 Jun 201649. NICE's rejection of Imbruvica 'reveals appraisal process flaws' [http://www.pmlive.com/pharma_news/nices_rejection_of_imbruvica_reveals_flaws_in_appraisal_process_947489]. Date accessed: 22 Jun 201650. Leyens L, Richer É, Melien Ø, Ballensiefen W and Brand A (2015) Available Tools to Facilitate Early Patient Access to Medicines in the EU and the USA: Analysis of Conditional Approvals and the Implications for
Personalized Medicine. Public Health Genomics 18(5):249-5951. Nivolumab Early Access to Medicines Scientific Opinion - Public Assessment Report The Medicines and Healthcare products Regulatory Agency
[https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/498155/Nivolumab_EAMS_15105-0002.pdf]. Date accessed: 22 Jun 2016
35© phamax AG, 2017- All Rights Reserved35
Acknowledgement
36© phamax AG, 2017- All Rights Reserved
Corporate Headquarters Bangalore Officephamax AG | Baarerstrasse 82 | 6300 Zug | Switzerland #19, KMJ Ascend | 1st Cross | 17th C Main | 5th Block | KoramangalaPhone +41 61 821 56 87 | Fax +41 61 821 58 36 Bangalore - 560 095 | India | Phone + 91 80 6745 1111 | Fax +91 80 6745 1122
Singapore Officephamax Asia | 10 Anson Road | International Plaza #12-14Singapore - 079903 | Phone +65 97899119
THANK YOU