Creating collaborative systems to address orphan drugs in a sustainable way – update from Europe

Wills Hughes-Wilson, VP Global Public Policy & Government Relations, Sobi

Member of the EU Committee of Experts on Rare Diseases (EUCERD)

Chair, Joint European Industry Task Force on Orphan Drugs (EuropaBIO + EBE)

Orphan Café, Leiden, 30 May 2012

Orphan Medicinal Products – “a balancing act”

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• Sense of urgency

• High, unmet medical need

• Serious, life-threatening conditions

• But few patients, few data

• Risk:benefit = positive

• Acceptance that it is ethical to move forward

• (Regulatory) acceptance, despite overall weight of

evidence not so available

• Compared with more common conditions

Results of the approach =drugs are being developed & approved

3

0

10

20

30

40

50

60

70

80

90

ODs with EU Positive Opinion ODs removed from EU Community Register

* 3rd Quarter 2011

“Balancing act” creates uncertainty –and has an impact on all stakeholders

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• Victims of success of the Regulation?

• ~55 therapeutic areas = “4,945 to 6,945 still to go?!”

• Governments seeking to understand the value of

what they are being offered

• How can we tell?

• Small datasets, surrogate endpoints, non-routine clinical

trial design, early approval…

• Some of the systems tried to date – NL – have

reportedly not been so successful for governments?

• “IS IT SUSTAINABLE?” Financially? Socially?

Creates a gap between Marketing Authorisation(EU) & Access to Patients (Country / EU Member State)

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Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011

Data Assessment Appraisal

This is important because…

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• Customers – those who pay* – are thinking about

value

• What is it?

• How do they measure it?

• What is it worth?

* Gatekeepers to patient access…

Situating the approach toorphan drugs in the wider external context

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1. Evolving cooperative environment between HTA

bodies – cross-border cooperation

2. Legislation to address uncertainty – new

Pharmacovigilance legislation

“Orphan” & “non-orphan”

tools exist to make it possible

• “Cross-Border Healthcare

Directive” creates legal

framework for further

cooperation

• Rare Diseases as a focus

Healthcare provision

remains a Member State responsibility

…but no longer in isolation

1. “Cross-Border Healthcare Directive” – 9 March 2011

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• European reference networks (Article 12)

• Explicit focus in regular reporting (Article 20)

• Permanent Network of HTA bodies (Article 15)

• Rare Diseases as a particular focus (Article 13)

2. New Pharmacovigilance Legislation

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• …“post-authorisation efficacy studies where

concerns relating to some aspects of the efficacy of

the medicinal product are identified and can be

resolved only after the medicinal product has been

marketed”

• PRAC requirements captured in CHMP Opinion

• Post-Marketing-Authorisation data-gathering

• Coordination vital – building on early dialogue

What is true for drugs generallyis PARTICULARLY true for orphan drugs

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October 2008: Grouping of 27 Member States agree

principles on orphan drugs as area of focus because

“these [orphan] medicines amplify strongly the

common tensions we have found in the field of

pricing and reimbursement: assessing and

rewarding innovation is difficult, budget

optimisation is challenged and access for patients is

limited in several countries”.

Countries facing the same questions –Collaboration & cooperation as a way forward

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• Particular need in the case of orphan drugs: rarity –

data & expertise

• Assessments need Methodologies & Agencies

• Takes time & resources

• Sharing / building something together rather than

creating de novo 27 times

• Best practice, experience

• Particular political focus on rare diseases & Orphan

Drugs with actions

European initiatives will interact to createthe framework for understanding orphan drugs

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1. CAVOD – Clinical Added Value of Orphan Drugs

2. MOCA – Mechanism of Coordinated Access to

Orphan Drugs

3. EUCERD Work Programme

4. National Plans for Rare Diseases

5. …the future?

1. CAVOD

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Gap between Marketing Authorisation (EU)& Access to Patients (Country / EU Member State)

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Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011

Data Assessment Appraisal

Four key time-points in the processof an orphan drug where collaboration could help

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1. Early dialogue

2. Compilation report & evidence-definition /

Evidence-Generation plan

3. Follow up of the Evidence Generation Plan

4. Assessment of Relative Effectiveness

� Respecting the roles and responsibilities within the

existing system

� Breaking down “silos” – bridging the gap

Time

Orphan

Designation

Significant

Benefit COMP

Protocol

Assistance

CHMP Opinion

T0

EC Marketing

Authorisation

T0 + 90 days

T0+∆T

(after 3-5 years, flexible,

depending on the disease

Period 1:

For EMA / EUnetHTA

coordination

Period 2:

For simple

Compilation report &

evidence generation plan

Period 3:

For follow-up of the

evidence generation plan

Period 4:

Relative effectiveness

assessment

Early DialogueCompilation Report

& Evidence Needs Identification

• EMA

• EUnetHTA

• Sponsor

1st assessment

of Significant

Benefit

Confirmation of

Significant

Benefit

• EMA (Report)

• EUnetHTA

• EMA

• EUnetHTA

• MAH

Evidence generation Assessment

• EUnetHTA

• EMA

• Could be

implemented

already

• Actions required?

• Report could be implemented

immediately

• Involvement with PRAC

requirements needs more work

• Evidence generation plans

& follow-up would need to

be defined

• Other?

• Appropriate

methodologies / tools

for OMPs to be

developed

Characteristics to aid success

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• Case-by-case

• Heterogenous conditions, therapies, situations

• Voluntary

• Respecting the systems, roles & responsibilities

• Multi-stakeholder involvement

• Developing the right tools for the job

• Measured

• Does it work? Periodic reporting

Formulating Policy into Reality:where in the process & what next?

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• 26-27 January 2012 – EUCERD endorses direction

• 9 May 2012 – updated by EUCERD drafting group

• 19 June 2012 – enlarged drafting group

• 20-21 June 2012 – EUCERD Plenary (adoption?)

[or November 2012 EUCERD meeting]

• Next steps from relevant authorities to implement

• Start with what we can: pilots by year-end?

“Oil in the machine”, not a new machine

2. MOCA

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Gap between Marketing Authorisation (EU)& Access to Patients (Country / EU Member State)

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Timeline graphic courtesy of Ernst & Young, CAVOD study, December 2011

Data Assessment Appraisal

Mechanism of CoordinatedAccess to Orphan Drugs (MOCA)

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• Create a tool for governments at time of pricing &

reimbursement

• Create (more uniform) access

• Control costs?

• “Whoever wants to give access” – have a “tool at

hand that he/she could follow”:

• From identification of potential solution (orphan drug)

• Through identifying what it’s worth

• To delivering to actual treatment of patient

• 15 countries – to create shared mechanism

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Mechanism of Coordinated Access

to Orphans

FR

UK

ESPT

IT

DE

CZBE

NL PL

RO

BG

EL

IE

HU

SE

FI

AT

CY

LT

LV

EE

DK

SKLU

SL

HR

SR

MK

BH

AL

CH

NO

UKR

UK

RUSSIA

TR

BY

IS

Will join

But it is not a closed club!

Member States can sign

up at any time to participate

in developing the mechanism

Shared mechanism betweenthe 15 countries involved

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Identifying and assessingRelevant OMPs – procedural steps flowchart

Start: Rare Disease Classification

Orphan Drug Designation by COMP

Coordinated Horizon Scanning

Early Dialogue

Advice Incorporated into Clinical

Development Plans

Marketing Authorisation

Application

Marketing Authorisation Process

at EMACHMP Positive Opinion

Therapeutic / Scientific Compilation Reports**

End: European Commission Marketing

Authorisation

Early Access Programmes

(regulatory or country level driven)

Discussion with Member States

*

*

*/**

*Potential links with other Work Packages

** Potential link with other initiatives in development, e.g. the different stages in the proposed CAVOD

process

Operational

step

Implementing

activity

Output

EU level:

EURORDIS

Patients

associations at

national level

ORPHANET

EPIRARE

Number of patients in

each country affected

by the (rare) disease

and elegible for

treatment with

orphan

Patient number

identification (PNI)

(Selection of the target

population)

PNI as orphan

medicinal

product

designation

PNI as

Patients`

Associations

PNI as Platforms

ad hoc and

European/nation

al Registries

Valuable

orphan

medicine

(WP1)

IRDIRC

National

centres of

reference

Analysis of pricing

systems for orphans in

MS

Actual costs of medicine/s

(transparent mechamism of

calculation) (Transparent

Pricing Matrix)

Rule-based Ceilling

price/threshold per

drug/disease

Expenditure forecast

(affordability)

Framework

Agreement with an

award decision/

statement of ceiling

price and/or MEA)

National

procedures for

P&R (local MS

price)

National

reimbursement

and price decision

Joint

Procurement

Pricing/Procurement

(Funding mechanism)

Outcomes on

affordability,

costs and

profitability

Negotiations

based on health

impact*

Joint Reimbursement by

Health Impact Fund (for

innovation) and by member

states (for production costs)

Alternative

mechanism*The Health Impact Fund is a proposed new way of paying for pharmaceutical innovation. a firm agrees to provide its drug at cost where it is needed, and in exchange for foregoing the normal profits from

drug sales, the firm is rewarded based on the HIF’s assessment of the actual health impact of the drug. Payors would finance the HIF. See http://www.yale.edu/macmillan/igh/.

This scheme was developed for financing drugs in developing countries. However, it may be adapted for financing orphan drugs.

Parameter Lower Degree Medium Degree High Degree

1:2 000-1 to 1:20 000 1:20 000 to 1:200 000 less than 1:200 000

Number of Patients in EU (Pop. 500

000 000) 25 000 to 250 000 2 500 to 25 000 less than 2 500

Available Alternatives/Unmet Need

(Innovation)

yes, new drug does not address unmet

need

yes, but major unmet need still

remains

no alternatives except best supportive

care - new drug addresses major

unmet need

Relative Effectiveness, Degree of Net

Benefit (Clinical Improvement,

QoL, etc. vs. side effects) relative

to alternatives

incremental major curative

Response Rate (based on best avialable

selection criteria)<30% 30-60% >60%

Degree of Certainty (Documentation) promising but not well-documented plausible unequivocal

Replaced by a proposedmulti-criteria approach to understand value?

…under discussion

Timelines & next steps

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• 27 April 2012 – MOCA Topic Leaders finalise draft

• 11 May 2012 – workshop 15 countries +

stakeholders

• Summer 2012 – write-up of project proposals

• November 2012 – presentation of final report

• END-2012 – delivery of final product

• Final report

• TOOL

• Manual of definitions, objectives & instructions

3. Specific approaches & programmes to buildsystems for orphan drugs

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Elements from Commission Communication will combine to build true “Eco-System” for Orphan Drugs

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CHAPTER 5 includes actions on:

• Centres of Expertise & EU Reference Networks

• Access to Orphan Drugs

• Compassionate Use programmes

• Incentives for Orphan Drug development

• Screening practices

• Diagnostic laboratories

• Research & development

• Registries & databases

Individual “how to” elementsbeing developed by the EUCERD

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EUCERD: EU Committee of Experts on Rare Diseases

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• 27 EU Member States (1 + 1 alternate)

• Patients

• Industry

• Academia / representatives of European-funded projects

• European Commission, ECDC

• EMA, COMP – request to be present

• 3rd Countries [non-EU]

The EUCERD’s role is to aid the European Commission

with the preparation and implementation of

Community activities in the field of rare diseases.

Individual “how to” elementsbeing developed by the EUCERD

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• Quality Criteria on Centres of Expertise: Oct 2011

• Recommendations on CAVOD (under consideration)

• Draft Recommendations for European Reference

Networks (in process)

• New-Born Screening in Europe – proposals for next

steps (under discussion)

• …

4. National Plans for Rare Diseases

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Political commitment by 27 EU governments for National Plan for RD in each EU Member State by 2013

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If plans are similar,

they can link

together to create

a European area

for rare disease

diagnosis,

treatment,

research…

Collaborative work to build National Plans continues

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• EUROPLAN recommendations adopted

• New EUCERD Joint Action (funding) includes further

work with countries

• 20 new conferences 2012-2013

• Indicators, measurables and success criteria

• EUCERD will report formally

• Potential benchmarking report by European

Parliament

5. The future…?

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The proposed Rare Disease treatment paradigm – the model for the future of sustainable healthcare systems?

37

Commission

Communication

Council

Recommendation

Treatmentc

- Effective

- Cost-effective

- Sustainable

- Meeting payers’ needs

Centres

of

Expertise

Registriesc

Could this be the way forward for all innovative drugs?

Confirmed

Diagnosis

Dose

adjustment

Outcomes

CAVOD

HTA

(Rel. effectiveness)

Reimbursement

/ Reimb. revision

CUP / Reimb. (in dev.)

THANK YOU!

wills.hughes-wilson@sobi.com

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