Insights into the Big5EU pricing & reimbursement potential of a novel cell therapy currently in early clinical development

Transcription

1 Insights into the Big5EU pricing & reimbursement potential of a novel cell therapy currently in early clinical development November 2014 Catapult is an Innovate UK programme.

2 Case study overview This case study is on a novel cell therapy which is in the early stages of clinical development: It is an allogeneic therapy It is a hospital-only therapy The size of its target population across the Big5EU is ~10,000 The Health Economics and Market Access team of the Cell Therapy Catapult undertook an assessment into the pricing and reimbursement potential of this therapy in order to: Assess commercial opportunity across the Big5EU Guide evidence generation activities during clinical development so that data requirements for market access can be met at launch Build a value proposition encompassing the most impactful clinical and economic drivers so that price and market access opportunity is maximised For the purpose of confidentiality the product and the target indication have been anonymised 2

3 Developing a robust pricing strategy involves leveraging multiple frameworks Methodology Triangulation QUAL/QUANT PRICING METHODOLOGIES PRICE The role of health economics varies by geography HEALTH ECONOMICS ANALOGUE ANALYSIS 3

4 We employed a combination of health economics, analogue analysis and pricing research frameworks to assess reimbursed price potential Phase 1 Health Economics (HE) & Analogue Analyses First, we identified a healtheconomically justified price based on: The clinical and economic burden of the target population The Target Product Profile (TPP) of the novel cell therapy The cost-utility methodology applied by NICE (England) Based on the HE analysis and market access insights from analogues, we developed hypotheses on the interrelationship between therapeutic positioning, pricing and reimbursement Phase 2 Key Market Access Stakeholder Engagement Through discussions with key market access stakeholders, we tested our hypotheses and generated further insights into: The key value drivers of the novel cell therapy Willingness to pay Supporting data requirements for market access optimisation Phase 3 Market Access Strategy Development We consolidated the findings from previous phases, and proceeded with the analysis and the development of conclusions and recommendations including: Interrelationship between positioning, pricing and reimbursement Revenue-maximising price Data generation activities for market access optimisation 4

5 We followed the principles of value-based assessments and linked price potential to the magnitude of the novel therapy s addedvalue over the standard of care PRINCIPLES OF VALUE-BASED ASSESSMENTS V = RV + PDV - NDV Reference Value of Standard of Care (SOC) Comparative data against the SOC is required: PDV Negative differentiation value (NDV) Positive differentiation value NDV Comparative, head-to-head (H2H) data demonstrating superiority or non-inferiority of Product X against the SOC is preferred Indirect comparisons of high methodological standards usually sufficient for noninferiority claims RV Reference value (SOC) V Differentiating Value e.g. Clinical effectiveness Economic impact: budget impact, costminimisation, cost-effectiveness, cost-utility Value (V) For a given indication, V varies depending on the intervention s positioning in the treatment algorithm and the target patient profile 5

6 QoL (utility score) The novel cell therapy meets the selection criteria for NICE s Technology Appraisal (TA), and we therefore used incremental cost-effectiveness as the measure of value Given the size of the target population, the anticipated incremental benefit and the cost of the novel cell therapy, it is expected to meet the selection criteria for a NICE TA Cost B Cost A ICER= QALY B QALY A QALYs = Life expectancy (life years) x Quality of life (utility) Costs Utility determined by EQ5D in TPP B = novel cell therapy A = standard of care Only direct healthcare costs were accounted for; wider societal impact was not included Treatment A 1 2 Life Years Treatment B QALYs gained (B vs A) NICE ICER thresholds: As the novel cell therapy does not meet the end-of-life criteria, the 20-30K/QALY applies; exact figure depends on: The degree of certainty around the ICER How adequately the change in HRQoL is captured How innovative the technology is 6

7 Based on the NICE TA framework, and the incremental benefits of the novel cell therapy, we identified the price ceiling that meets the ICER threshold 50,000 45,000 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 Price potential of novel cell therapy (split by its value components) 0 Value of QALY gain Outpatient/primary care savings Savings in hospitalisations Through systematic evidence review we identified the clinical and economic burden associated with the target patient population; we accounted for: Current therapeutic approaches and probability-based clinical, Quality of Life (QoL) and economic outcomes We then applied the outcomes described in the Target Product Profile (TPP) to assess the impact the novel cell therapy has on the above parameters Using the ICER threshold of 30K we calculated a health economically justified price ceiling Through sensitivity analysis, we assessed the impact changes in certain TPP parameters have on the price potential 7

8 To calculate the ICER of the novel therapy we developed a costutility model that captures key health states, time-dependent transitions, outcomes and uncertainty In developing the model we accounted for: Target population/position in Tx algorithm Comparators (alternative strategies) Perspective (NHS) Time horizon (based on survival data) Health States Outcomes: cost, utility and life years Model Type: State transition Markov model Analysis: Cohort simulation, Microsimulation Sensitivity analysis: Deterministic: univariate / multivariate Probabilistic (parametric) Structural 8

9 Given a certain level of uncertainty in model variables, the health economically justified price results in the majority of ICER values falling below the WTP* threshold ICER scatterplot generated through a Monte Carlo simulation Software: TreeAge Pro 2014 * WTP: Willingness-to-Pay 9

10 We then accounted for variations in pricing frameworks across countries and adjusted the health economic argument accordingly HTA value drivers by market Country A B C D E Clinical Effectiveness illustrative QoL Cost utility Cost consequence Budget impact Cross country price referencing 10

11 Subsequently, we explored how the HE argument resonates with key market access stakeholders across the Big5EU, as well as willingnessto-pay, therapeutic positioning and supporting data requirements Main Objectives of Market Access Stakeholder Engagement 1. Identify clinical and economic considerations for assessments at national, regional and local level for a hospital-only cell therapy 2. Explore perceptions of key market access stakeholders of the differential value of the novel cell therapy over existing treatments 3. Explore impact of clinical and HE arguments on willingness to pay and use the novel cell therapy 4. Explore interrelationship between supporting data, price potential and likelihood of restrictions being imposed 5. Generate insights into the data inputs for the economic models and their countryspecific adaptation 6. Explore funding mechanisms outside the DRG/HRG tariffs 7. Shape future evidence generation activities and value story Scope: France Germany Italy Spain UK 11

12 National level Regional level National level Understanding the relevant national, regional and local market access processes for a given cell therapy is key in formulating an effective key stakeholder engagement strategy Stakeholder engagement strategies need to take into account the specific features of a given cell therapy Market access routes, decisionmakers, evaluation methodologies and funding options can vary depending on: Regulatory status E.g. ATMP, non-medicinal cell therapies, cell therapies not intended for licensing, Early Access Schemes Size of target population Setting of care E.g. centre of excellence; inpatient vs outpatient Unmet need, magnitude of incremental benefit claims and costs Market Authorization EMA ANSM National level Clinical evaluation SMR CT Reimbursement rate UNCAM ASMR ASMR I, II, III ASMR IV, V Economic evaluation CEESP Cost-effectiveness Price negotiation CEPS Inclusion on Hors T2A list (outside DRG) Council of hospitalization (Ministry of Health) Local Level Inclusion in hospital formulary COMEDIMS Market Authorization Clinical evaluation GCPT Therapeutic positioning report Market Authorization EMA PEI Process for obtaining additional funding Hospital P&T Committee NUB funding for 1 year Local Level Price & reimbursement CIPM Budget impact HTA / Budget impact analysis (for retail drugs) Local Level EMA Clinical and economic assessment GENESIS Group Regional authorities Hospital P&T committees Assessment of eligibility for NUB status INEK NUB funding negotiation + + No additional funding - AEMPS Inclusion in hospital formulary HICs Literature review MDS Arbitration Board Inclusion in Hosp formulary Hospital P&T Committees - National level Regional Level Local Level NICE* (formal assessment) NHS commissioning (Specialized Services) NHS hospitals Market Authorization Clinical evaluation AIFA - CTS Innovation level and reimbursement status Price negotiation AIFA - CPR Budget impact HTA / Budget impact analysis/ Funding pathway Regional authorities DRG Local Level Horizon Scanning Center DoH/NICE/NHS Topic selection EMA / MHRA Clinical Reference Groups ASLs EMA File F AIFA Inclusion in hospital formulary Specialized Hospitals 12

13 Key market access stakeholder engagement We applied the Value Curve* methodology to identify the most impactful clinical and economic drivers of the TPP * Evaluated by utilising a value curve methodology to derive relative value of product attributes (Kim WC and Mauborgne R [1997] Value Innovation: the strategic logic of high growth. Harvard Business Review [January- February]: ) Presentation Indication Off-the-shelf allogeneic cells Treatment of Disease X Efficacy Primary endpoint: Induction of remission by day 28 X% of patients on active vs Y% of patients on comparator Secondary endpoint: Complete response by day 28 X% of patients on active vs Y% of patients on comparator Additional endpoints: Progression-free survival at day 180 X% of patients on active vs Y% of patients on comparator Additional endpoints: Overall survival at day 180 X% of patients on active vs Y% of patients on comparator Additional endpoints: % patients with remission at day 28 who survive to day 90 without rescue therapy X% of patients on active vs Y% of patients on comparator Safety and Tolerability Pharmaeconomic and QoL outcomes Dosing Administration VALUE CURVE METHODOLOGY* No cell related adverse events No treatment limiting immunogenic effects Low procedure related AEs: <X% (patients fully recover with no long-term consequences and no prolonged hospital stay) Significant Reduction in Outpatient visits X% RR Significant reduction in length of in-hospital stay X% RR EQ-5D questionnaire : X% change from baseline LS Mean (95% CI) vs comparator 2 million cells/kg twice over 1 week Infusion Overall Value Key Value: 1 = no 5 = highest 13

14 The most impactful clinical and economic drivers formed the basis for the value story and the planning of data generation activities, while accounting for individual market HTA requirements The pyramid structure depicts the transition from the target value proposition, to a series of value claims and the corresponding supporting data requirements Value Proposition Value Claims Summary of incremental value of novel cell therapy over existing treatments Series of value claims related to: unmet need; clinical benefits; patient benefits; economic benefits Supporting Evidence Clinical and economic supporting evidence 14

15 Key market access stakeholder engagement We assessed reaction to the health economically justified price and willingness-to-pay by applying a van Westendorp pricing methodology 100 Point of indifference 90 % of respondents Point of marginal expensiveness Fully Too cheap Justified Too Expensive expensive Not Expensive cheap Not Justified expensive Range of target prices for a breakthrough therapy Price ( 000s) Price per course (Euros) 15

16 Too Low Optimal Key market access stakeholder engagement Price Too high Simultaneously we explored the interrelationship between willingness-to-pay, reimbursement restrictions and supporting data requirements At higher prices, the risk of restrictions increases as well as the requirements for subpopulation analysis, long-term data generation and risk-sharing agreements Potential consequences Requirements for favourable access Expensive 50,000 Limited use or reimbursement, significant restrictions Marginally Expensive 48,000 Used and reimbursed for majority of eligible patients, limited restrictions Price indifference 32,000 Widely used with full reimbursement Substantial concerns over budget impact Delays in getting reimbursement/risk of no coverage Severe subpopulation restrictions o For those who would benefit the most as determined by subpopulation analysis e.g. Resistance in usage e.g. o Head of department priorauthorisation Reimbursed for majority of eligible patients Some risk of restricted usage e.g. o In subpopulations of greater unmet need o Specialist-center only (decreased access to patients in some regions) Subpopulation specific data demonstrating incremental benefit o Product will be restricted in the subpopulations of highest unmet need and who benefit the most Discounts Over 2 years safety and efficacy data Robust plans for manufacturer sponsored real-world data generation / registries Risk-sharing agreements Advocacy group support There will be a tendency for payers seeking longer-term data; Risk-sharing schemes can help bridge any data gaps Registries/real-world data generation Use according to label Registries/real-world data generation 16

17 Key market access stakeholder engagement % of patients ; Revenue Index By accounting for the correlation between price, reimbursement restrictions and uptake, the price-volume trade off curve was generated and the revenue-maximising price identified Gabor Granger Methodology Derives a relationship between price and market share and identifies a revenue-optimal price Treatment cost (, 000) The price and volume interrelationship is used to inform forecasting and therapy valuation The impact of supporting data on pricing and reimbursement help inform the magnitude of investment required in data generation activities and the likely return-on-investment The development of the individual country pricing strategy, the exploration of the impact of cross-country pricereferencing and the identification of the optimal launch sequence are reserved for the later stages of the therapy s clinical development 17

18 Pricing and reimbursement decisions are not always fully aligned with funding; the criteria and processes for the latter were identified to provide a cohesive market access strategy Funding mechanisms for high-cost innovative hospital products (outside tariffs) Funding mechanisms by country Applicability of decision Relevant budget Eligibility criteria for additional funding Hors T2A list Country level National budget NUB/ ZE Hospital level Health Insurance Companies budgets ASMR score of I, II or III (moderate to major improvement over SOC) Existing DRG funding is insufficient Therapy is <3 years on the market Existing DRG funding is insufficient File F Regional level Regional budgets At regions discretion (no formal criteria) Regional list of expensive therapies Regional level Regional budgets Ex-PBR National NHS England At regions discretion (no formal criteria) Positive NICE and/or Specialised Services (under NHS England) opinion Existing PBR funding is insufficient 18

19 Supporting Data Requirements We formulated recommendations on trial design and further data collection based on the consolidated findings from the HE analysis and the market access stakeholder engagement The key recommendations on optimisation of supporting data covered: Clinical Trial design Inclusion criteria Trial duration and size Comparators Clinical endpoints PRO/QoL endpoints Economic endpoints Clinically significant differences (Minimally Important Differences) Subpopulation analysis (A priori vs. Post-hoc) HE model inputs Feasibility of indirect comparisons Post-launch data generation activities Major therapeutic improvement Important therapeutic improvement Moderate therapeutic improvement Minor therapeutic improvement No therapeutic improvement Data requirements are proportionate to the magnitude of incremental benefit claimed 19

20 Cell Therapy Catapult 12th Floor Tower Wing Guy s Hospital Great Maze Pond London SE1 9RT +44(0) Catapult is an Innovate UK programme.