Understanding Regulatory and Payer Requirements Throughout Commercialization
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Learn about regulator and payer evidence requirements as well as other key market access considerations in drug development. Read this presentation from PAREXEL Consulting experts.
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Understanding Regulatory and Payer Requirements Throughout Commercialization
- 1. © 2018 PAREXEL INTERNATIONAL CORP. UNDERSTANDING REGULATORY AND PAYER REQUIREMENTS THROUGHOUT COMMERCIALIZATION Gema Parlange Vice President and Worldwide Head, Access Consulting, PAREXEL International April 17, 2018 PAREXEL KOREA SYMPOSIUM 2018
- 2. © 2018 PAREXEL INTERNATIONAL CORP. / 2 THERE IS AN INCREASE IN R&D SPEND WITH A PARADIGM SHIFT IN DRUG DEVELOPMENT…
- 3. © 2018 PAREXEL INTERNATIONAL CORP. / 3 … WITH NARROWER INDICATIONS AND SMALLER PATIENT POPULATIONS BUT UNCHANGED EVIDENCE REQUIREMENTS… • Narrower indications (e.g. oncology) to reduce uncertainty and risk • Specific gene mutations • Stage • Biomarkers • Each licensed indication allows potential access to a smaller number of patients • More specific evidence required per indication and to extend to another line of treatment
- 4. © 2018 PAREXEL INTERNATIONAL CORP. / 4 INCREASE IN EARLIER CLINICAL DATA PACKAGES (E.G. PHASE I/II SINGLE ARM STUDIES) WITH THERAPIES INCREASINGLY COMING TO MARKET AT EARLIER STAGES OF THEIR CLINICAL DEVELOPMENT… Regulatory overview / summary Regulatory hurdles The hurdle for regulatory approval is changing Emergence of transformational therapy classes
- 5. © 2018 PAREXEL INTERNATIONAL CORP. / 5 Quality1 Safety2 Efficacy3 Value4 Regulators Payers Key considerations of… Focus of… Hurdles to Patient AccessHurdles to patient access THE PARADIGM SHIFT IN DRUG DEVELOPMENT MUST SATISFY BOTH REGULATORS AND PAYERS Comparative benefits Real-world effectiveness Economic value Typically single trans-national bodies (e.g., FDA/EMA) with similar focus Range of national, regional and local payers by market with differing foci
- 6. © 2018 PAREXEL INTERNATIONAL CORP. / 6 AS SHOWN WITH EFFECTIVE ADVANCED THERAPY MEDICINAL PRODUCTS NOT ACHIEVING COMMERCIAL SUCCESS DESPITE MARKETING AUTHORISATION… Source: Macaulay R, ISPOR 2017 Increased early engagement to consider regulatory and payer perspectives will improve chances of access to effective medicines
- 7. © 2018 PAREXEL INTERNATIONAL CORP. / 7 AND COMMERCIAL CHALLENGES WITH NEW AND EFFECTIVE THERAPIES OVER PRICING STRATEGY Pricing and implications • Hepatitis C – highly effective treatments with 95%+ cure rates significantly improvement • Pricing and budget impact: treatment of all eligible patients was not feasible for national budgets, disparity of price between countries (movement of patients) • Competition: Later to launch, but ~30% discount resulted in uptake and positive perceptions • Impact: changes in national budget impact considerations – in anticipation for future curative therapies Prices, Costs, and Affordability of New Medicines for Hepatitis C in 30 countries: An Economic Analysis May 31 2016
- 8. © 2018 PAREXEL INTERNATIONAL CORP. / 8 … PRIOR EXPENSIVE PRICING SCENARIOS HAS CREATED PERMANENT CHANGES TO P&R PROCESSES… New P&R reforms in the wake of recent and future expensive therapies April 2017, any cost-effective new technology whose annual budget impact >£20 million in years 1-3 post- launch will have to undergo commercial discussions with NHS England to mitigate its financial impact New budget impact test Pilot preliminary results (March 2018) of cost-effectiveness (CE) assessments for 13 products in Japan: • Two price reductions Opdivo and Kadcyla) and one upward adjustment for a medical device Anticipated expansion of healthcare insurance in South Korea to increase focus on CE for expanded coverage Cost-effectiveness in Asia
- 9. © 2018 PAREXEL INTERNATIONAL CORP. / 9 … BUT HOW DO YOU APPROPRIATELY REIMBURSE THERAPIES WHERE UNCERTAINTY IS SO HIGH? High costs High benefits High uncertainty High risk Evidence Provisions of Expedited Pathways Increasing Evidence Demands of Payers Single-arm Phase I/II data Increasing approvals on Perhaps leading to conditional marketing authorization Increasing demand for Comparative Clinical Benefits Patient-Relevant Endpoints Robust Health Economic Analyses
- 10. © 2018 PAREXEL INTERNATIONAL CORP. / 10 RWE can bridge the gaps by helping to quantify and validate: … BUT COMPANIES CAN ALSO USE RWE TO BRIDGE THIS EVIDENCE GAP FOR OPTIMAL MARKET SUCCESS… Disease burden Clinical benefit Economic benefits Epidemiology treatment patterns unmet need Effectiveness safety performance-based pricing schemes Support cost- effectiveness and budget impact modelling
- 11. © 2018 PAREXEL INTERNATIONAL CORP. / 11 RWD CAN SUPPORT PAYER DECISION-MAKING FROM AN EVIDENCE, ECONOMIC AND HTA PERSPECTIVE How RWE can be used throughout the product life-cycle Proactively planning and implementing RWE to supplement regulatory submission data strengthens the evidence package as part of the commercial strategy • Understand the disease and market • Gather competitive intelligence • Set the stage • Begin assessing product use and outcomes • Respond to mandates • Optimize product use • Build body of evidence • Respond to market changes and new information • “Evergreening” Post-ApprovalPre-Approval At Launch
- 12. © 2018 PAREXEL INTERNATIONAL CORP. / 12 … WITH RWE ALREADY HAVING BEEN USED TO SUPPORT REIMBURSEMENT ACROSS MANY MARKETS Market Example(s)Scheme AIFA-Onco Registry established in 2005 – performance-based pricing well-established TASIGNA® (nilotinib) 2016 Cancer Drugs Fund reforms as a temporary reimbursement fund to collect RWE TAGRISSO® (osimertinib) Since 2011, Managed Entry Schemes allow dynamic pricing based on RWE In the last 3-4 years, a trend towards performance-based pricing schemes XALKORI® (crizotinib) REPATHA® (evolocumab) ENTRESTO (SAC/VAL) KYMRIAH (tisagenlecleucel)
- 13. © 2018 PAREXEL INTERNATIONAL CORP. / 13 … IT IS CRITICAL TO START WITH THE END GOAL IN MIND TO ENSURE COMMERCIAL SUCCESS LAUNCH PHASE III PHASE II PHASE I PRE- CLINICAL POST LAUNCH EVIDENCE GENERATION OPTIMIZATION ACCESS REALIZATION IDENTIFY HYPOTHETICAL VALUE PLAN FOR SUSTAINABLE VALUE CRYSTALISE AND COMMUNICATE VALUE PROTECT AND REFINE VALUE, IMPROVE UPTAKE
- 14. © 2018 PAREXEL INTERNATIONAL CORP. / 14 DECISIONS AND TRADE-OFFS EVOLVE AND ARE REQUIRED IN ORDER TO DEMONSTRATE VALUE What evidence is needed to demonstrate value? How to maximize the economic value? What is the potential economic value? How to ensure value is rewarded with maximum P&MA? How to generate evidence to demonstrate value? Time Cost Risk Uptake
- 15. © 2018 PAREXEL INTERNATIONAL CORP. / 15 KEY QUESTIONS Late phase Pre-clinical studies Phase 1 studies Phase 2 studies Phase 3 studies Evidence Evaluation Health Economic Modelling Pricing and Market Access Clinical Outcomes Assessment Real World Data Regulatory submissions Due diligence review for asset acquisition Clinical trial protocol development Evidence based prioritization Market access needs assessment and evidence generation Market access, pricing and reimbursement strategy Early asset prioritization/ portfolio review Organizational excellenceDue diligence Evidence reviews Epidemiology evidence strategy Early stage models HTA/reimbursement evidence strategy Evidence optimization COA strategy RWD long-term effectiveness studies Health economic models and analysis Network meta-analysis /comparative effectiveness research Local access strategy Value communications Global pricing & market access strategy Post marketing evidence plan Clinical development plan Cost effectiveness/utilities models Budget impact models Field based tools Country model adaptations RWD treatment analysis RWD data base mapping and assessment RWD cost- of illness studies RWD safety studies COA development &validation COA licensing, translation & migration to eCOA How to ensure value is rewarded with maximum P&MA? How to generate evidence to demonstrate value? What evidence is needed to demonstrate value? Market access submissions How maximize the economic value? What is the potential economic value?
- 16. © 2018 PAREXEL INTERNATIONAL CORP. / 16 SUMMARY Considering both regulatory and payer perspectives are critical with the changing treatment landscape and evidence requirements Commercialization strategy and planning should start from the end to ensure timely access Specific country requirements and the competitive landscape means that the commercialization strategy needs to be flexible and regularly updated
- 17. © 2018 PAREXEL INTERNATIONAL CORP. / 17 THANK YOU © 2018 PAREXEL INTERNATIONAL CORP. / 17
Notas del editor
- Increasing R&D spend is not correlating with new drug approvals The traditional model is no longer fit for purpose and there is a paradigms shift in drug development – no longer the era of a single blockbuster and large new therapy areas More than productivity challenges - It is not a question of the industry becoming more efficient (using old models). Its external https://www.theatlas.com/charts/VkX47L3O
- New treatments coming to market are increasingly in specialist areas or rare diseases Licensed indications tend to be narrow with many products (especially in oncology) having multiple indications – examples in figures (not to focus on detail), but molecular classifications for breast cancer and biomarker targets for lung cancer highlighted The end result is that each licensed indication allows potential access to a small number of patients Thus the combination of rising costs of evidence development and narrow patient populations drives higher prices in the face of cost containment measures Commercial strategy to maximize ROI is critical and the ways to generate and collect the data is changing Curigliano https://www.slideshare.net/ESOSLIDES/9-curigliano https://www.nature.com/articles/nrclinonc.2010.84
- Along with the narrower patient populations and potential multiple therapies, the treatments in these areas are more innovative and transformational, offering effective, potential curative therapies. A 10 year analysis by the EMA of conditional marketing authorisation, has shown that 50% of products have (some) results from a phase 3 study at MAA - The key is the balance of requirements, beneficial to promote access to patients , however, from a payer perspective they are viewing greater uncertainty than ever before to determine if the treatment is effective, safe and worth paying for [to add – potential questions on expedited approvals, orphan indications, immuno-oncology]
- There are 4 hurdles that a product must clear to achieve patient access Regulatory: Product is safe and efficacious as demonstrated through trial data Payers: Product will offer real-world clinical value over SoC and represents an optimal investment of limited funds Compounding even further is complexity of the payer landscape: multi-stakeholder and market specific– you need to know who all the stakeholders are, what their roles are and what they need, where the money is, how decisions are made, where the patients are and the patient journey disease specific – e.g. what goes for diabetes does not work for oncology
- Effective treatments for rare diseases have overcome the regulatory hurdle, but have not been prescribed or used in clinical practice. PAREXEL view: The failure of the effective treatments, emphasizes the magnitude of the commercial challenges faced by ATMPs including complex and costly regulatory and manufacturing processes, small patient populations with limited clinical data, and the need for high upfront investment for a course of therapy that may only be a single treatment PAREXEL solution: Earlier understanding of the payer and real world prescribing would be a critical step. Innovative payment models such as annuities/leasing and/or performance-based reimbursement may need to be explored to ensure patient access and commercial returns [Source: Macaulay, R ISPOR 2017] Opportunities for joint advice, showing the acknowledgement of both perspectives The European Medicines Agency (EMA) offers consultations in parallel with the European Network for Health Technology Assessment (EUnetHTA) as of July 2017 Seek feedback from regulators and HTA bodies on their evidence-generation plans to support decision-making on marketing authorisation and reimbursement of new medicines at the same time These consultations can take place before or after the product is made available on the market Parallel advice objectives is “to help generate optimal and robust evidence that satisfies the needs of both regulators and HTA bodies”. In PAREXEL’s experience, it is important to have these rounded views, and we can supplement with individual regulatory/payer consultations – but it is important to do this early when it is actionable So how do we best link the requirements and when should we be doing this…? [build to next slide]
- Case study: Not a case of charging the highest price possible and also implications as we have the advance of new curative and highly efficacious end-of-life therapies create unique challenges [Unanonymised example] First to market: Gilead launched Sovaldi in the US at $84,500, followed by a combination treatment, Harvoni for $94,5000 for a 12-week regimen Budget impact: If CDC estimated 3.5 million Americans with HCV were treated then it would cost $331 billion, which was more than total drug spending in 2013 Price disparity: 3-month treatment in Egypt dropped from US$900 in 2014 with movement of foreign patients seeking treatment Competition: Merck’s later entry Zepatier was priced at $54,600 in the US with positive support for improving access Future implications: In the UK, NICE has requested that any treatment with a budget impact over £20m in any of the first three years after launch will require further negotiations Deciding the correct launch and pricing strategy is critical… Would company have altered their pricing strategy (launch price and cross-country pricing strategy) or are they satisfied with the trade-offs that they decided (public perception and criticism, future budget impact challenges)?
- While cost-effectiveness is not a key decision driver in Asia, the use of analysis in Japan suggests a potential trend towards consideration as a supporting part of negotiations. This raises issues of how to effectively develop such economic model (requires country specific data: utilization, resource use - which can be addressed by RWE) Japan CE changes (further details): Chugai's (Japan) cancer treatment Kadcyla (trastuzumab emtansine) received a CEA-related reduction in its National Health Insurance (NHI) price of 1.5%, from JPY235,108 (USD2,205) to JPY231,532 and according to Pharma Japan, a 90% reduction of the treatment's initial pricing premium PD-1 inhibitor Opdivo (nivolumab; Ono Pharmaceutical, Japan) also received an undisclosed downwards price adjustment after the treatment received an NHI price cut of 23.8% earlier in March Kawasumi Laboratories' (Japan) Kawasumi Najuta Thoracic Stent Graft System is expected to receive an undisclosed upward price adjustment
- Another critical component is that of uncertainty. The potential impact on the patient could be transformative but if the product gains market authorisation through a reduced evidence plan, then there will be a range of uncertainty. In the example on the previous slides, a substantial gain in expected survival is likely to have been projected from a much shorter follow-up or estimated from a surrogate endpoint (otherwise we would not be talking about limited evidence …) Assumptions would have been made about sustained QoL (ditto …) Hence this results in a huge range of uncertainty (assumptions = uncertainty) In fact, we usually think of evidence development as a process for reducing uncertainty
- In order to address these tradeoffs, RWE being used to span this gap by quantifying and validating disease burden, clinical and economic benefits in a number of meaningful ways. RWE can support and supplement the evidence package or help facilitate negotiations by addressing existing data gaps or uncertainty. Often forgotten, but RWE can be used to help with internal decision making as well, to understand or determine the target patient population, differentiate, differences between trials and real world practice…
- If not planned from an early stage – there is a lost opportunity for potential pre-approval and launch activities that would provide the strongest supporting evidence or delays as the evidence is then collected afterwards Pre-approval: Better understand the disease or condition: Identification, diagnosis, treatment, outcomes, patient preferences, natural history, cost of illness, quality of life, payor mix Develop foundation for value proposition and market-access strategies Establish / grow sponsor’s leadership position and franchise within the market - relationships with KOLs Develop ‘distribution channels’ Set foundation for FDA, EMA, other mandates Set foundation for assessing changes in treatment market following product launch At-launch Optimize physician and patient use of the product Begin to develop long-term, comparative, observational dataset Set foundation for assessing changes in treatment market following product launch Identify patient-selection criteria at launch Assess quality of life, economic impact Respond to mandates for PASS/PAES (post authorisation safety/effectiveness studies) Post-approval Generate critical scientific assessments Assess the condition’s changing profile Monitor safety signals and trends Identify and evaluate key patient sub-groups Enhance market understanding Understand changes in patient-selection criteria over time Assess changes in market as treatment options and approaches evolve Support sponsor and product positioning Further sponsor’s leadership position within the market Maintain product relevance and success – “evergreening’ using patents and other exclusivity periods likely contributes to the total incentives that justify a pharmaceutical company's investment in a new drug.
- Thom
- Question is that during early phases and planning, how much consideration is there for the requirements of the countries and local access considerations? Considerations regarding the largest markets, prioritization and active decisions and compromise made? Is there a voice at the table to reflect launch and post-launch considerations and implications? Connected journey should have the end (commercial strategy) in mind at the start as one of the key factors for decision making It will not be the final solution and will need refinement, but should not be ignored Should not be a siloed activity or a last minute consideration Without having the commercial and market access considerations as part of the trade-offs in early decision making ROI, commercial success, patient access should not be forgotten – implications if disconnected or unplanned Early planning with end goals in mind ensures informed and proactive decision making rather than reactive, sub-optimal responses. Allows considerations of trade-offs that will shape and form the strategy [Add case studies: inappropriate trial comparator and lack of feasibility to allow an indirect comparison to HTA required comparator, which could have been addressed if considered during the trial design and endpoint selection] [Q: operational challenges and views – barriers to implementation. Respond with that the initial investment will reap rewards with the process optimized and rolled out across compounds/indications]
- The questions that we answer change as the product advances along the development pathway: We begin by understanding ‘what is the potential economic value of the compound’? Is it worth the investment? We then assess ‘how can we maximize the value of the compound’? What should we prioritize? Then we determine ‘what evidence is needed to demonstrate the economic value of the compound’? What evidence is needed to satisfy payers? How can it be produced? Then we explore ‘how can we generate the evidence needed to demonstrate economic value of the compound’? We produce the evidence! Finally we answer ‘how can we ensure the economic value is rewarded with maximum price, reimbursement and market access’? We develop and execute the strategy! Example scenarios to highlight Racing to being first to market vs. third-fourth to market Cost of generating new evidence and the returns from it (critical, nice-to-have, only required in one market) Balancing the risk of delays, negative results For product development, there is no one-size-fits-all approach. Most efficient pathway to launch does not necessarily mean the most evidence – a lean and fast strategy could bring greater returns due to time on market, planning to have the critical evidence generated rather than huge volumes of data that may not be required. Strategy is the balance of the trade-offs and the choices made. Should be proactive rather than reactive
- SPEAKERS NOTES: In summary, our work helps our clients to optimize price, volume and, ultimately, revenue throughout the development, launch and marketing of their product The questions that we answer change as the product advances along the development pathway: We begin by understanding ‘what is the potential economic value of the compound’? Is it worth the investment? We then assess ‘how can we maximize the value of the compound’? What should we prioritize? Then we determine ‘what evidence is needed to demonstrate the economic value of the compound’? What evidence is needed to satisfy payers? How can it be produced? Then we explore ‘how can we generate the evidence needed to demonstrate economic value of the compound’? We produce the evidence! Finally we answer ‘how can we ensure the economic value is rewarded with maximum price, reimbursement and market access’? We develop and execute the strategy!