MAPPs: Medicines Adaptive Pathways to Patients Removing Regulatory Barriers and Fostering Greater Collaboration Presentation MAPPs are the continuous evaluation of new therapies which reacts to their actual performance in patients over the entire lifecycle of the treatment The goal of MAPPs is to balance timely access for patients with the need to provide evolving information a new therapy’s benefits and risks. MAPPs are being piloted in Europe, and we believe MAPPs will eventually incorporate adaptive clinical trial design, patient centric benefit/risk assessment and continuous evaluation as new real-world evidence becomes available. Such a pathway should enable rapid adaptations based on patient responses. www.efpia.eu

Science is leading the revolution in targeted, personalised therapies: More precise diagnosis based on specific bio-markers of the patient Effective treatments designed to target the underlying cause of the disease Smaller, faster clinical trials Drugs given to those most likely to benefit Less waste + toxicity as we target those most likely to benefit MAPPs will harness many of the scientific breakthroughs being advanced by stratified (personalised) medicines. We have the technical ability to now move beyond a ‘one size fits all’ approach to treatment, we should also be investigating ways to do this in evaluating the effectiveness of new therapies to bring them to market Stratified/personalised medicine also means that we can focus treatments on responders, and do so with less toxicity as we will only treat those people where we see effectiveness of treatments.

The stakeholder relationships for MAPPs visualized The stakeholder relationships for MAPPs visualized. No longer is the regulatory process a series of bilateral discussions between a drug company and a regulator, payer, HTA, etc in a linear fashion… The evidence required and ‘success metrics’ are agreed in advance, and the performance of the therapy is evaluated based on actual evidence generated by how the new therapy performs in patients.

MAPPs imply that ALL stakeholders in the decision making process are involved at the start of designing the MAPPs trial. The evidence required and ‘success metrics’ are agreed in advance, and the performance of the therapy is evaluated based on actual evidence generated by how the new therapy performs in patients.

How Will MAPPs Benefit Stakeholders?* For patients and providers Earlier access to promising new medicinal products Lower realised harm Continuous reduction of uncertainty throughout the lifetime of the product New risk management paradigm that may restore public confidence For regulators Adaptive reimbursement plan to align value with price and utilisation Continuous risk/benefit information flow to better support (follow-on) coverage decisions For payers For the pharmaceutical industry Earlier revenue stream; staggered development costs Decrease risks of (costly) late stage failures and post-market withdrawals This slide must not be skipped. Here we outline the changes needed for the 5 key stakeholder groups to improve regulatory pathways and what the impact of these changes will be. * Based on HG Eichler’s presentation of 4 June 2015

What will change with MAPPs? Transition from … Magic moment  focused life-cycle management Prediction  monitoring and adjustment RCT only  toolkit for evidence generation Big populations  focused populations Emphasis on licensing emphasis on patient access Open utilisation  evidence based utilisation

EMA Adaptive Licensing Pilot EMA has 58 applications as of April 2015, of which roughly one-third have been selected for further discussion Majority of the therapies submitted project are not for primary care use, but would need to be delivered by highly specialised care centres Tools are needed to stimulate designing non linear adaptive pathway, as current pilots are essentially linear in design EMA seeks three tools to assist pilot project: Patient engagement tool allowing in a reproducible way to gage willingness to accept uncertainty Evidence generation linking data from primary care, tertiary care, and hospital databases Model that could help evaluate and design a pathway that considers all the stakeholder opinions simultaneously Implementation of more creative intelligence to get marketing authroisation https://www.youtube.com/watch?v=JIhMCl5Gceg This slide gives an update as of May 5, 2015, as to the status of the EMA MAPPs pilot. If you have time and the technical capability, the youtube link is a video of Hans-Georg Eichler articulating the EMA position of the pilot.

Coordination and Support Action (CSA) in IMI Medicines Adaptive Pathways to Patients seek to foster access to beneficial treatments for the right patient groups at the earliest appropriate time in the product life-span in a sustainable fashion www.adaptsmart.eu Demonstrated potential benefit Continuous monitoring of a new therapy Measurement and adjustment over the entire lifecycle Objective measures, including real world evidence MAPPs is a key platform of many projects working under the Innovative Medicine’s Initiative under Horizon 2020. IMI2 is a nearly 4 billion Euro public private partnership combining the resources of EFPIA, the European Commission, and many leading EU research institutions in the 28 member states MAPPs activity in IMI2 will be managed in a multi-stakeholder Coordinated Support Action, also in partnership with MIT’s NewDigs.

MAPPs is a key platform of many projects working under the Innovative Medicine’s Initiative under Horizon 2020. IMI2 is a nearly 4 billion Euro public private partnership combining the resources of EFPIA, the European Commission, and many leading EU research institutions in the 28 member states MAPPs activity in IMI2 will be managed in a multi-stakeholder Coordinated Support Action, also in partnership with MIT’s NewDigs.

MAPPs Myths Dispelled “MAPPs only “works” in Rare Diseases” Many aspects of Rare Disease R&D fit with MAPPs but applicable to all areas of development “R&D investments will be lower under MAPPs than Traditional development pathways” Investments before first approval lower, but higher post-launch – company may need to build monitoring infrastructure Lower sales volume after initial targeted approval, but earlier patient access; indication broadens out over time and volume then increases Costs of failure may increase due to accelerated investments (eg manufacturing, parallel work) “Product prices will be lower under MAPPs than traditional development pathways” More targeted patient populations may gain greater health benefits (and therefore value) – even if not fully demonstrated at launch. Investments and risks may increase or decrease Value provided to patients who are within treatment window.

Development Access Regulatory HC delivery Early patient access: combination of existing and new tools within the current legal framework Development Access Regulatory HC delivery GetReal Early and continuous dialogue Big Data for Health Outcomes PAES & PASS Patient preference elicitation for B/R ADAPT SMART REA/HTA Conditional marketing authorisation Rolling review Managing Uncertainties Parallel Scientific & HTA advice Compassionate Use/Early access schemes Pricing/Reimbursement Full marketing authorisation (evt. Subject to conditions) MEAs Accelerated assessment (and decision making)

Summary MAPPs is a paradigm shift that requires new ways of thinking, operating and behaving MAPPs need “safe harbours” to test new models and ideas – EMA pilots and IMI collaborations MAPPs requires an open and early dialogue of all players in the research and healthcare eco-systems

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