Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
Pricing and Market Access Challenges for Payers in Europe
Presented by:
Mondher Toumi, MD, PhD, MSc
ISPOR Lebanon Chapter – 22 February 2019
What are the payers doing? Examples from Europe
Table of contents
1. Pharmaceutical landscape overview
2. Context and Pressure of High Prices
3. Unprecedented Rapid Pace of Innovation
4. Cost Containment and Complexity
5. New Development program, regulatory processes,
and payer uncertainty
6. From Decision Point to Decision Window
7. From Selling Drugs to Selling Outcomes
8. HTAs & Payers are focused on the Real World
9. Integrated Health Care System
10. Hospital Restricted Distribution
11. Price as a Powerful Optimisation Tool
12. Payers, Politicians, and Society
Pharmaceutical landscape overview
4
Healthcare Expenditure in Europe
5
% of GDP Allocated to Healthcare
9
11
13
15
17
19
21
2006 2009 2012 2015 2018 2020
% G
DP
US OECD ex-US
6
Innovation Pillars for Pharmaceuticals
1
Prevent copy cat
• Patent
• Data protection
2
Value based pricing
• Often unknown and source of multiple confusion
7
Pharma Payer Landscape is Evolving in a Multidimensional Context
Healthcare budget pressure
Rapid pace of
therapeutic innovation
Increased aversion to uncertainty
Change in healthcare services organisation
Unfavorable Context for high prices While increase pressure for high prices
9
Current situation
While the healthcare
budget is decreasing
the number of very
promising molecules in
development is
increasing
10
Widening the gap?
Unsustainable gap between healthcare
expenditure level on one side and ,
affordability and demand on the other
side
11
For the first time a company went bankruptcy because of an excessive price
Dendreon is planning to charge $93,000 per patient for Provenge.
Dendreon stock: 25 percent to over $50 after price disclosed.
Provenge is too expensive to be used on the NHS in England,
Dendreon, filed for bankruptcy protection
Provenge sales were hampered by the drug’s high cost of $93,000
We are facing an unprecedented rapid pace of innovation
13
Genomics is a moving target
Adenocarc
inoma
Squamous
Large-cell
Traditional view
Unknown
KRAS
1987
Unknown
KRAS
EGFR
2004
Unknown
KRAS
EGFR
EML4-ALK
HER2
BRAF
MET
AKT1
MAP2K1
PI3KCA
2009
Pao, Lancet 2011 Kris et al, JAMA 2014
14
Treatment in lung cancer
KRAS Mutation: associated with response or resistance to
particular therapies
EGFR Mutation: predicts for sensitivity to EGFR tyrosine kinase
inhibitors (TKIs)
ALK translocation: presence of an ALK translocation strongly
predicts for sensitivity to ALK tyrosine kinase inhibitors
MET amplification: one of the potential molecular mechanisms
of acquired resistance to EGFR-TKIs
ROS-1 fusions: can be used to offer targeted treatment with
criozitinib.
Source: 1Korpanty, G. J., Graham, D. M., Vincent, M. D., & Leighl, N. B. (2014)
15
939 clinical trials for ATMPs
54%
22%
23%
1%
Somatic cell medicinal product SCMP
Gene therapy medicinal product GTMP
Tissue engineered product TEP
Combined product
Government 5%
Hospital 31%
Institute 20%
Medical center 7%
University 37%
Categories Sponsors Commercial 26%
Non-commercial
74%
16
Bending the cost curve in oncology
58
13
30
38
39
34
176
30
25
26
28
58
338
43
71
Other
Transplantation
Skin diseases
Respiratory disorders
Neurologic disorders
Musculoskeletal disorders
Infectious diseases
Genetic disorders
Eye conditions
Digestive disorders
Diabetes/ related conditions
Cardiovascular disease
Cancer/Related conditions
Blood Disorders
Autoimmune disorders
Biologic Medicines in Development - by Therapeutic Category Some medicines are listed in more than one category
PhRMA, report Biologics, 2013
Almost 40% of cancer therapies are biologics accounting for $100 billion in
sales (Kozlowski S et al, The New England journal of medicine 2011; 365(5): 385-8.)
17
Pharmaceutical companies need to engage with payers and regulators at an early clinical development stage to ensure clinical trials are designed to maximize the chance of successful reimbursement, to
optimize non-clinical elements of the appraisal process, and to begin early negotiations for a mutually agreeable reimbursement strategy.
Early Dialogue
To allow pharmaceutical companies to gain critical insights from HTA bodies and regulators early in the development of a medicine, generally before
initiation of phase III clinical trial
To help pharmaceutical companies ensure that their technology development plan is appropriate and to optimize evidence generation and address HTA
bodies’ needs
To increase the probability of a positive outcome during drug assessments and to speed up market access. Frequent engagement with regulators during
all phases of development and commercialization help the agencies to understand challenges.
Parallel advice may help to harmonize HTA and regulators’ perspectives and provide manufacturers with recommendations to achieve market access for
ATMPs
Early
Dialogue
Objectives
• Publishing best practices and consensus papers in collaboration across industry and regulatory bodies will enable the
development of a knowledge base and harmonized standards.
Cost containment is expected to remain the preferred payer’s tool While Complexity for access will increase
19
All is About Affordability
US society accept to pay increase in life expectancy of 1.2 months $80,000
Extrapolation survival of 1 year is valued at $800,000
550,000 Americans die of cancer annually
To extend their life by one year 440 billion would be needed
Even US will not afford it
19
20
Cost Containment Tools
Restricted
distribution Restricted
prescription
Budget cap
for
therapeutic
class
Price cut
Budget cap
per product
Reduce
reimburse
ment
External
reference
pricing
Bundled
payment
Price
volume
agreement
Index
brand
prices on
generic
Restricted
to hospital
use
21
Budget Impact Cost-
Effectiveness
Lesson from sofosbuvir from cost-effectiveness to budget impact
New Development program and regulatory processes
to increase payer uncertainty
23
From a Trend to Reality
Source: Eichler H.-G., Bloechl-Daum B., Abadie E., Barnett D., König F. and PearsonS. Outlook: Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers Nature Reviews Drug Discovery 9, 277-291 (April 2010)
Dedicated relative efficacy/
effectiveness assessment ?
•Quality, safety, efficacy
•Benefit-risk profile
•Cost vs health benefit
•Budget impact
•Relative efficacy/effectiveness
•Emphasis on RCT, most often
active- and placebo-controlled
•Cost-effectiveness/utility analysis
•Budget impact analysis
•Active-controlled RCT
•Adaptive Phase III-IV trials
•Observational studies
•Meta-analysis
Assessors
Assessment focus
Studies/data
MA Current paradigm Regulators
Payers
Tomorrow
Future paradigm
24
New Regulatory Processes is widening the gap with payers
• Regulators impact: earlier availability for patients
• Payers impact: level of evidence is lower
*access before marketing authorisation is granted
Introduction
of adaptive
licensing
Approval
under
exceptional
circumstanc
es
Early entry*
Conditional
approval
25
New Development
• Highly sliced population
• Benefits in small populations
• Request for crossover for ethical reasons
New developments involved highly
targeted therapies
• Considerable potential social value
• Low level of payers evidence
• Difficulty to quantify the benefit Payers impact
From Decision Point to Decision Window It is Already There, we Just have not Realised it yet
27
The Window is Already Here
Country MA CP Final Window
Risperdalconsta France 07/01/2003 10/02/2005 End 2010 7 years
Sitagliptin
France 21/03/2007 03/2008 2010 (End of CED ) 5years
Scotland 03/2007 09/2007 06/2010 3.25 years
Duodopa Sweden 2002 2003 2008 6 years
Some examples are well known and widely communicated in literature
28
Time Limit G-BA Resolutions
Vemurafenib (1 y) Sitagliptin (2 y) Vandetanib (3 y)
Crizotinib (2 y) Sitagliptin/metf (2 y) Axitinib (4 y)
Eribulin (2 y) Belatacept (3 y) Ipilimumab (5 y)
Saxagliptin (2 y) Cannabis sativa (3 y) Pertuzumab (5 y)
Saxagliptin/metf. (2 y) Fingolimod (3 y) Bosutinib (5 y)
Window from 1 to 5 years
Example of GBA decision window
From Selling Drugs to Selling Outcomes A Major Model Shift for the Industry
30
There is
no uncertainty
about the cost
of medicine
Payers Buy a Proxy of Health
We need health but we buy a proxy: healthcare
Medicines are intended to produce health
When funding medicines, payers intend to buy health production
31
Shift in Payer Model
The promised benefit must be evidenced in real life clinical practice
Outcomes must be shown in well designed real world studies with limited or no intervention on the field or within databases
The internal validity will be the door entry outcome
The external validity will be the value acquired by payers
HTAs & Payers are focussed on real life.
But what is real life?
33
Randomized double blind two arms clinical study
Behaviour is articificial and may not exist in real life
34
Pragmatic/observational study
Try to mirror natural behaviour but still some control
35
Real life evidence Requested by HTA and Payers
Often impossible to capture.
Need database analysis /
observational studies
coupled with modelling to simulate
real life condition
36
Prescription population
Disease
Target
Treatment
Efficacy
Failure
37
Dispensation
Disease
Specialists
GPs
Hospital
Pharmacists
38
Disease complexity
Disease
Moderate
Mild
Severe
Disease 2
± treatments
Disease 3
± treatments
Disease 4
± treatments
Disease 5
± treatments
39
Real life is complex and often confusing
Disease 2
± treatments Disease 3
± treatments
Target
Efficacy
Failure
Treatment
GPs
Pharmacists
Disease
Moderate
Mild
Severe
Specialists
Hospital
Disease 4
± treatments
Disease 5
± treatments
Need to design a specific study for a specific question.
When behaviour is critical databases allow to ensure unbiased behaviour.
When a question is Complex, a model become unavoidable
40
Place of digitized medecine and big data in real life information
Electronic-health-records
Computer based medical decision
Lost of clinical power in Rx decision
Police role: Early access to practice and fast reaction
Policy role: analysis of best practice and understanding of drivers of cost and outcomes
Access to who?
• Information remain fragmented and heterogeneous
• Next step challenges to integrate the data in a single warehouse
Integrated Health Care System The new way for the future?
42
Changes in Health Care Services Organisation
New funding model: from fee to services to outpatient service and all
other related ancillary services included into a lump-sum payment
Shift of decision-making from payers to healthcare providers
- 42 -
Integrated healthcare systems Hospitals, multispecialty care delivery, other
services, and coverage integrated into a
comprehensive system for delivering care
43
Five popular ACO payment models
ACO model of payments
• providers can share in a portion of the savings they achieve in a modified fee-for-service model
"One-sided" shared savings
• providers take on downside and upside risk in this fee-for-service based payment model
"Two-sided" shared savings
• providers get a single payment for all of one patient's services for one episode of care
Bundled/episode payments
• providers receive preset payments per patient in return for providing whatever services are needed, combined with payments based on actual services performed
Partial capitation/global
payments
• provider organization assumes a great amount of risk with global payments. With this arrangement, providers receive monthly or annual payments, regardless of the care services they performed in that time period.
Global payments
ACO may use a range of payment models (capitation, fee-for-service with
asymmetric or symmetric shared savings, etc.)
44
DRGs for outpatient services
Ambulatory Patient Group (APG) is a classification system for outpatient services reimbursement developed for the American Medicare service by the Health Care Financing Administration (since 2010)
APG reimbursement system does not recognize units of service.
• Nutrition counselling
• Crisis management
• Patient education including diabetes
• Asthma self management services
• Health/behavioral assessments
45
Bundled Payment
• Bundling payment of drugs to procedures, (mirror Hospital DRG)
• Example of ESA bundled to dialysis
• Tenders become systematic
• Competition driven by prices
• Price discount up to 80%
• Shift of power negotiation from payers to healthcare providers
Hospital restricted distribution
47
Impact of Distribution of Biosimilars through Hospital (million €)*
0
1000
2000
3000
4000
5000
FR DE EL HU PL PT UK
Base case Exclusive hospital distribution
Biosimilar savings
Assuming 80% price discount
versus brand
*Health care public payer perspective
Price as a powerful optimisation tool But may be dangerous too
49
The Pricing Lock
49
25 years after GSK tritherapy we are back with Gilead.
50
Financial toxicity: An elephant in the room
• Discussion with patients about
financial concerns represents
a clear unmet need
• Many patients who are
insured do not have adequate
drug plan coverage and end
up in bankruptcy.
• This has become socially
unacceptable
51
The Power of 1%
Source: Compustat, McKinsey analysis
19.2
68.3
12.5
100.00
Revenues Fixed Costs Variables Costs Operating profit
Price increase Profit increase
1.0% 8.0%
Payers have not shown to be creative nor ambitious They are just reactive Politician will unlikely act Society will react
53
Need to change business model
From selling drugs to selling outcomes
From controlling drug distribution to patient management
Multi-companies alliance to access information and impact outcomes
Anticipate the future pricing landscape or loose the battle
Pharma is likely to dominate the game but for how long
54
Uncertainty will remain the critical issue
Albert Einstein
“As far as the laws of mathematics refer to reality, they are not certain;
and as far as they are certain, they do not refer to reality.”
Albert Einstein
56
Pricing of Generics vs. Pricing of Innovative Drugs
While most countries regulate prices of generics to secure savings (price linkage) …
• France: 60% of originator price
• Latvia : 30% of originator price for the first generic, then 10% less for the followings, then 5%
… Prices of innovative drugs (ATMPs particularly) have reached unprecedented prices
and continue to increase
Example of ATMPs’ Prices authorized in Europe
Brand name Manufacturer Authorization date Market Withdrawal Price at market entry
US$
Gene therapy
Glybera® UniQure 10/25/2012 10/28/2017 $1,206,751
Strimvelis® GlaxoSmithKline 5/26/2016 Marketed $738,223
Imlygic® Amgen 12/16/2015 Marketed $357,309
Kymriah® Novartis 8/22/2018 Marketed $441,538
Luxturna® Spark Therapeutics 11/23/2018 Marketed $425,000
Tissue-engineered products
ChondroCelect® TiGenix 11/16/2009 7/29/2016 $21,926
MACI® Vericel 6/27/2013 09/05/2014 $21,926
Holoclar® Chiesi Farmaceutici 2/17/2015 Marketed $93,432
Spherox® Don AG 07/10/2017 Marketed $18,950
Cell therapy
Zalmoxis® MolMed Spa 8/18/2016 Marketed $814,780
Provenge® Dendreon 09/06/2013 05/06/2015 $110,920
57
Patient Access Scheme in UK
• The terms of individual agreements are confidential.
• Discounting levels vary considerably, often reflecting the price must be reduced in order to meet
the cost-effectiveness thresholds applied by NICE:
• Generally applies an ICER threshold of £20,000–30,000 per QALY gained (raised to $50,000
for end-of-life treatments, higher for ultra-orphan drugs
• As of January 2018, 140 schemes are listed on NICE’s website
Few new drugs are recommended by NICE for routine NHS commissioning without the provision of
a discount.
Patient Access Schemes (PAS) are a formal part of the pricing and reimbursement environment in
the UK, commonly represented by simple discount
Source: Barham L, 2015
58
The French ATU, granted and controlled by the ANSM, allows a compassionate use of drugs provided the following characteristics are met
• Treatment of rare or serious diseases
• No Marketing authorization yet
• No suitable therapeutic alternative in France
• Efficacy and safety are presumed
• Benefit is expected for the patient
Early Access to innovative Drugs in France Authorization for Temporary Use (ATU)
The purpose of the “ATU” is to provide an early access to some promising medicinal
products that do not have a marketing authorization where there is a public health need.
• Concerns a single patient (by name)
• Granted for the duration of the treatment
• Issued at the request and under the responsibility of
the prescribing physician
• Safety and efficacy data are collected according to a
protocol for therapeutic use
“Nominative ATU” “Cohort ATU”
Pre - Marketing
Authorization
• Granted for a one-year duration (renewable)
• Group or sub-group of patients treated and monitored
following the criteria defined in a protocol for
therapeutic use
59
The French RTU, elaborated and controlled by the ANSM, allows to monitor off-label prescribed medicines provided the following characteristics are met
• Therapeutic need is unmet (no appropriate alternative medicine with a marketing authorization or a cohort ATU in the designated indication)
• Benefit / risk ratio is assumed to be favorable based on the available scientific efficacy and safety data
Off-Label Use in France Recommendation for Temporary Use (RTU)
The objectives of the RTU are to render the use of off-label prescribed medicines safer
• Applies to drugs with a marketing
authorization in France
• On a temporary basis (3 years)
• Upon request and under the responsibility of
the ANSM
• Efficacy and safety data are collected and
annual reports are sent to the ANSM
RTU Conditions 25 RTU granted as per Feb 2019
2014 2 Lioresal®/Baclofene Zentiva®, Roactemra®
2015 6 Avastin®, Cirdacin®, Stelara®, Thalidomide
Celgene®, Velcade®, Verapamil®
2016 4 Hemangiol®, Methotrexate®, Truvada®,
Xalkori®
2017 3 Uvesterol ADEC®, Novoseven®, Remicade®,
2018 10 Gymisio®/Misodone®, Keytruda®, Inspra®, M-
M- Rvaxpro®, Opdivo®, Tafinlar®, Vindaqel®,
Avastin®, Cirdacin®, Remicade®
Post - Marketing
Authorization