Alicia Granados: Adaptive Pathways and Lifecycle Approach (ADAPTSMART

Medicines Adap,ve Pathways for Pa,ent (MAPPs) / AdaptSmart

Canadian Expert Pa.ents in Health Technology Conference Nov 7-‐8 2016 Toronto, Canada Alicia Granados MD, PhDPH Sanofi Genzyme

© Copyright IMI ADAPT SMART | This project has received funding from the Innova,ve Medicines Ini,a,ve 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innova,on programme and EFPIA.

Outline

•  Context •  Some Challenges of Access to Innova,on •  MAPPS / IMI/AdaptSmart an update •  Aspects for further reflec,on from EMA pilots •  Next steps •  Final Comments

Disclaimer: •  This presenta,on reflects my own personal perspec,ve and by no

means expresses a company posi,on. •  My thoughts should offer a view in order to s,mulate discussion


Context The Road of Innova,on to Approvals & Reimbursement

•  Safety & Efficacy

Regulatory Filing

•  Relative Safety •  Relative Efficacy •  Relative Effectiveness •  Cost- effectiveness

HTA Assessment

Product Reimbursement


Challenges in Access to Innova,ons Level of agreement in product-‐specific advice EMA vs HTA

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40

60

80

100

Population Endpoints Comparator Recommendation

HTA

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N = 56 products

http://www.efpia.eu/documents/189/61/HTA-Accelerator-In-Depth-Analysis-Final-report

21 October 2016


Challenges in Access to Innova,ons Variability in HTA prac,ces

2016 Industry Metrics Study


Challenges in Access to Innova,ons Cri,cism of Exis,ng Paradigm

•  Poor alignment between regulatory and HTA eviden,ary requirements

•  Poor alignment between HTAb eviden,ary requirements

This has resulted in:

•  Different decisions between regulators and payers , but also different recommenda,ons between HTAb

•  Technology development inefficiencies that are ,me-‐ and resource-‐ intense

•  Delayed pa,ent access

•  Increased uncertainty for Industry and Investment decisions in R&D are less effec,ve and R&D processes less efficient

From: Possibilities for harmonization of reimbursement (HTA) and regulatory processes and evidentiary requirements in Canada [Internet]. [Internet]. [Updated 2013 May 6; cited 2015 Feb 10]. Available from: http://www.slideshare.net/CADTH_Symposium/a4-panel-discussion-possibilities-for-harmonization-of-hta-and-regulator-processes-and-evidentiary-requirements-in-canada-goeree-drummond-tsoi-sabourin-henshall-salon-b

Current EU Landscape on Multistakeholders Initiatives for Collaboration ..

- -

Adaptive pathway •Accelerated pathway for therapies indicated for serious conditions with high unmet needs •Iterative development with use of real-life data •Ability to engage various stakeholders including regulators, companies, health technology assessment (HTA) bodies and patient representatives in multiple discussion along the development pathway

Priority medicines (PRIME) scheme •Accelerated assessment of medicines of major public health interest and unmet medical needs •Scientific advice at key development milestones, with the potential involvement of multiple stakeholders including HTAs/Payers and patient bodies where relevant

EMA-HTA parallel scientific advice •Scientific advice of EMA in parallel with HTA bodies

Multi-HTA advice •The SEED Consor,um (Shaping European Early Dialogues), led by the French Haute Autorité de Santé (HAS) consists of 14 national and regional HTA bodies •The SEED consortium is developing a proposal for a permanent model for Early Dialogue that will govern the process in 2016

National HTA advice •Several countries put in place HTA early advice for clinical development plan of health technologies

EUnetHTA pilot assessment of relative effectiveness •Process put in place by the EUnetHTA to test methodology, procedures and national/local implementation of joint rapid relative effectiveness assessments and to test the capacity of national HTA bodies to collaborate and produce structured rapid core HTA information on relative effectiveness


Medicine Adap,ve Pathways to Pa,ents (MAPPs) •  Adap,ve pathways is a scien'fic concept of medicines development and data genera'on intended for

medicines that address pa,ents’ high unmet medical needs.

•  It can be defined as a planned, progressive and adap,ve approach to bringing a medicine to pa,ents

Adap,ve Pathways is based on three principles:

1.   Itera've development which means ini,al focus on a narrow, well-‐defined pa,ent popula,on with the prospec,ve planning of possible expansion of the indica,on to other pa,ent popula,ons (www.ema.europa.eu)

2.   Early dialogue with mul,ple stakeholders (regulators, HTA agencies, pa,ent and healthcare professional representa,ves) in a ‘safe harbour’ environment to discuss the clinical development program of a promising new medicine before large confirmatory trials are planned;

3.  The use of real-‐world evidence to supplement clinical trial data;

EMA MAPPs Pilots experience so far..

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•  EMA MAPPS pilot started in March 2014 with the aim to explore the practical implications of the adaptive pathways concept with medicines already under development

•  62 applications, of which 18 were selected for in-depth, face-to-face meetings with the participation of relevant stakeholders, and covering a wide range of therapeutic areas

•  Seven of these applications progressed to a formal scientific advice or parallel regulatory-HTA

scientific advice •  One in four products had been granted orphan designation by the European Commission

•  Majority of the proposals received did not fulfil the eligibility criteria for the pilot, and applicants were advised to pursue traditional development routes


“Accelerated Development of Appropriate Pa,ent Therapies: a Sustainable, Mul,-‐stakeholder Approach from Research to Treatment-‐outcomes” ADAPT SMART is a Coordina,on and Support project funded by IMI Started in September 2015; dura,on 30 months Consor,um includes 32 partners represen,ng pa,ents, academia, regulators, Health Technology Assessment (HTA) bodies and industry (public-‐private partnership) Payers are observers Goal:

•  Establish a plakorm to facilitate and accelerate the availability of MAPPs. •  MAPPs seeks to foster access to beneficial treatments for the right pa,ent groups at the

earliest appropriate ,me in the product life-‐span in a sustainable fashion Deliverables:

•  Horizon scanning •  Analysis of gaps, enablers and barriers to MAPPs •  Recommenda,ons and poten,al op,ons

Total cost € 2 260 000


THE INNOVATIVE MEDICINES INITIATIVE (IMI) The Innova,ve Medicines Ini,a,ve (IMI) is Europe's largest public-‐private ini'a've aiming to speed up the development of bemer and safer medicines for pa,ents. IMI supports collabora've research projects and builds networks of industrial and academic experts in order to boost pharmaceu,cal innova,on in Europe. IMI is a joint undertaking between the European Union and the pharmaceu,cal industry

associa,on EFPIA.


MAPPs Seamless Pathway and Decision Points

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Core MAPPs Moment Description of the Process Step / Decision Point

Development assessment Prior to making a decision for a product to enter development, the developer assesses the

opportunity of a potential medicine, for example, considering general input from multiple stakeholders and MAPPs’ criteria.

Agreement on commitment to MAPPs

Stakeholders offer a collective, documented decision under “safe -‐harbor” discussions regarding their commitment to progress with a MAPPs engagement approach for a particular potential medicine.

Iterative development plan In contrast to the traditional sequential development plan, an iterative development plan refers

to an evolving product development strategy, which integrates the advice of the stakeholders ahead of time.

Authorisation Regulatory decision to authorise a medicine for effective patient use in a given therapeutic indication(s).

Appraisal / pricing considerations

Evaluation of the medicine’s relative effectiveness and pricing and reimbursement decisions.

Patient use The foundation for the MAPPs concept is to provide patients who experience a high unmet medical need with an initial or improved treatment option through tools to enable an acceptable degree of on-‐label prescribing.

Reassessments Represents the post-‐authorisation decision-‐making points where new knowledge is gained and

used to inform an assessment of patient use of the medicine. This includes potential adjustments of reimbursement or price -‐ informed by real world evidence

Traditional Model While technically not a core MAPPs moment, a product, once progressing under MAPPs, may no longer meet the selection criteria and therefore potentially transition to the traditional model.


Iden,fying Enablers and Barriers of MAPPs Moments

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Stakeholder Enabler Barrier Pa'ent

(inc advocacy, representa'ves)

•  Access to ,mely and correct informa,on and resources to make an informed decision

•  Understand the benefit: risk preference from the whole community (≠ personal preference)

•  Poten,al lack of relevant exper,se and knowledge of regulatory, HTA/payer process

•  Funding and opportuni,es to ac,vely engage with decision processes

Health Care Professional •  Expert knowledge on the condi,on and product to make an informed decision (AE’s, indica,ons)

•  Infrastructure for addi,onal RWD collec,on

•  Different exper,se will be required at the different decision making points.

•  Many experts involved in prescribing, •  RWD collec,on •  Shared understanding of off label – on label and in

development indica,ons. Medicine Developer •  Deep knowledge of pathophysiology and of disease

course •  Priori,ze early access in the development plan •  Use of mixed methods for development program for

RWE genera,on

•  More intensive management of itera,ve processes (funding and personnel)

•  Vulnerability: Financial, IP and early knowledge sharing •  Behavioral changes required from all internal and

external stakeholders •  Understanding where MAPPs fits within other

regulatory tools and early access schemes

Regulator •  Quality Infrastructure for addi,onal RWE collec,on •  Clear agreements between all stakeholders (non

binding vs binding) •  Access to early dialogue with all stakeholders •  Proac,ve pharmacovigilance

•  More intensive management of itera,ve processes

HTA/Payer •  Control of ‘off label’ use •  Access to early dialogue with all stakeholders •  Managed entry agreements to control uncertainty •  Quality Infrastructure for addi,onal RWE collec,on

•  More intensive management of itera,ve processes (funding and personnel)

•  Complexity of MEA – many possibili,es •  Disparity of payer remit across EU member states •  Behavioral changes required from all stakeholders


Recognize Heterogeneity and Complexity AND

Make it Ac,onable

Highligh,ng the Right Issues


MAPPS. Some cri,cisms and poten,al solu,ons Adap,ve pathways have its strong advocates but the concept has also received cri,cism from various stakeholders¡ including HTAs. Some examples

•  “Adap,ve pathways proposes early market introduc,on based on less comprehensive evidence which could mean a marke,ng authoriza,on would be granted based on a smaller RCT that could leave HTA decision-‐makers with considerable uncertainty regarding a product’s added value”

ü  Sort of Managed Entry Agreements linked to RWE genera,on seems to be one of the an,dote to these uncertain,es , but building trust is also key

•  The MAPPs concept may either exacerbate or raise new ethical and legal concerns and opportuni,es from the pa,ents’ and clinicians’ point of view with respect to appropriate prescribing and use by target groups, and for Industry from a liability point of view.

ü  A MAPPs product has a marke,ng authorisa,on. Therefore, the current legal status quo prevails in terms of promo,on, liability and prescrip,on

ü  Any nega,ve outcomes under MAPPs (i.e. change in risk/benefit, withdrawal) could be challenged as it could be today

Ques,ons s,ll to be solved

Whether and how to control prescribers behaviour?

Whether and how to control access (public vs private access)?

Agreeing to something then withdrawing consent?

How can understanding & communica,ng risk and uncertainty to pa,ents and prescribers be maximized?

How best to address perceived increased risks in liable claims?

How can we minimize legal and ethical differences for informed consent, liability and prescrip,on control across different EU states

How can I get out of here?

How can I cancel my booking?

Where and when does the journey

end?

What are the safety measures if the plane crash?

What are the compensa,ons if the plane is delayed?

Aspects for further reflec,on : Disengaging from MAPPS?


Aspects for further reflec,on from both, EMA pilots AdaptSamrt workshops •  The need for increased involvement of pa'ents to assist in the selec,on of candidates for adap,ve

pathways.

•  The defini'on of methodologically-‐sound strategies of real-‐world evidence collec'on to support the assessment of both efficacy and effec,veness.

•  The poten,al involvement of payers -‐ Member States’ organiza,ons responsible for decision on pricing and reimbursement – to provide input on pricing strategies.

•  Adap've pathways makes use of exis'ng approval tools, in par,cular condi,onal marke,ng authoriza,on which has been in opera,on in the European Union since 2006.

•  As for any medicine, a marke'ng authorisa'on will only be granted if the balance of benefits and risks for a defined pa'ent popula'on is found to be posi've; the same principles and legal tools apply as for any other new medicine.

•  Coopera'on between stakeholders and a strong pharmacovigilance system are the basis for a systema,c monitoring of the safety and the overall performance of a medicine in clinical prac,ce; these are the two key elements underpinning the adap've pathways concept


Next Steps

Early December, EMA will organise a workshop to gather the views and proposals from its stakeholders on the AP approach IMI ADAPT SMART is s,ll inves,ga,ng the conceptual framework that could be used in adap,ve pathways, including tools procesess and methodologies


Next Steps •  Keep Aligning understanding of all stakeholders

Ø  Not an exercise to create an (accelerated/new) procedure, including market access/ pricing guarantees

Ø  Case by case decision on engagement criteria reflecting an holistic view of development and market access

•  Constructive dialogue with all stakeholders – paving the way for MAPPs implementation in R&D Ø  Safe harbour to address any issue with willingness to succeed – no

taboos, with solution oriented collaboration •  Create operational predictability

Ø  A MAPPs road map on criteria, tools, methodologies, ‘types’ of stakeholders’ involvement at critical steps, data requirements and standards, timelines, facilitating investment decisions

•  MAPPs fitting in global development plans •  Continued engagement of all stakeholders post ADAPT

SMART


REGULATORS

Final reflec'ons Adap've pathways is s'll a developing concept which will be refined as more medicines are considered for this approach.

Mul'-‐stakeholder Collabora'on is

key in Genera'ng the Best Possible Knowledge and the Best Decisions


Back up slides

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Region Stakeholder(s) Type of Interaction

Australia TGA, PBAC Parallel submission/review

Australia TGA, PBS Scientific advice on development

Canada Health Canada, CADTH Parallel submission/review and scientific advice on development

England MHRA, NICE Scientific advice on development

Sweden MPA, TLV Scientific advice on development

US FDA, CMS Parallel submission/review (devices)

US Multiple Stakeholders New Drug Development ParaDIGmS (NEWDIGS)

Europe EMA, EUnetHTA Revision of EPARs

Europe EMA, EUnetHTA Harmonization of HTA requirements (Guidelines)

Europe Multiple Stakeholders Medicines Adaptive Pathways to Patients (MAPPs)

Europe Multiple Stakeholders Join EMA /Multi- HTAs Parallel Scientific Advice (SEED)

Europe Multiple Stakeholders Innovative of Medicines Initiative (IMI)/ GetReal and Adapt Smart

Europe Multiple Stakeholders International Rare Disease Research Consortium (IRDiRC)

Europe EC, EUnetHTA, Member States European Commission Permanent HTA Network

Global Multiple Stakeholders Scientific advice on development (Green Park Collaborative)

Current Ini'a'ves on Mul'-‐Stakeholder Collabora'on

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ADAPT SMART – a Public Private Partnership

• Funded by IMI-JU • 01 June 2015 – 1 Dec. 2017

(30 months) • 22 EFPIA members • 2 patients’ organisations • 2 HAs, 2HTAs • Payers as observers • Total cost € 2 260 000

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The Consortium


I.   Drug Discovery

II.   Non-‐clinical

III.   Clinical Trials

IV.  Regulatory Review

V.   Post-‐marke'ng Ac'vi'es

VI.   Access Decisions

Adap've Pathway for Medicine Development and Commercializa'on

Development and Commercializa'on Phases Involved Stakeholders

Pa'ents

Health-‐care Professionals

Regulators

Health Technology Assessors

Payers

Medicine Developers

Decision-‐making Stakeholder(s) = Adap've Pathway Process Adjustment

Alicia Granados: Adaptive Pathways and Lifecycle Approach (ADAPTSMART

Healthcare

Transcript of Alicia Granados: Adaptive Pathways and Lifecycle Approach (ADAPTSMART