BOOSTING THE DEVELOPMENTOF RARE DISEASE THERAPIES: THE IRDIRC ORPHAN DRUGDEVELOPMENT GUIDEBOOK

Virginie HivertIRDiRC, Therapies Scientific Committee Vice-ChairTherapeutic Development Director, EURORDIS – Rare Diseases Europe

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Diego Ardigò

IRDiRC, Therapies Scientific Committee Chair

Global Rare Disease Unit, R&D Head, Chiesi group

(Italy)

Virginie Hivert

IRDiRC, Therapies Scientific Committee Vice-

Chair

Therapeutic Development Director, EURORDIS – Rare

Diseases Europe

A BIT OF HISTORY…

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Officially launched in 2011 under the impulsion of the European Commission and the US NIH to

accelerate medical breakthrough for People living with Rare Diseases

(PLWRD) by creating a network of research funders

Almost ten years later

The network has expanded:

• Funding organizations (i.e., funding bodies, groups of funders (for small funders), companies) investing more than 10 million USD over 5 years in rare disease research

• Umbrella patient advocacy organizations representing broad patients’ interests for all rare diseases in at least one country or larger area

ADDRESSING A TREMENDOUS UNMET MEDICAL NEED

IRDiRC Goal set up in 2011

200 new therapies by the year 2020

Achieved in 2017

Goal 2: by 2027, 1000 new therapies for rare diseases

will be approved, the majority of which will

focus on diseases without approved options

A quantum change of the presentdrug development model andecosystem for rare diseases isneeded.

The current rate of drug

development (40-50 new therapies

developed per year)

Only 5% of the 6000-8000

diseases with an approved

treatment

TSC roadmap

Support the definition of a new master plan for the

development and registration of innovative

drugs specific for rare diseases

From the current toolbox … … toward a new one.

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ORPHAN DRUG DEVELOPMENTGUIDEBOOKA patient focused guidebook that describes the available tools, incentives, resources and practicesfor developing traditional and innovative drugs/therapies for rare diseases and how to best usethem. It can be used by academic, non-profit organizations, small and larger (innovative) biotechsand patient-driven drug developers.

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ODDG – PROJECT AT-A-GLANCE 1 Workshop with 20 drug

development experts and stakeholders

1 milestone-based drug development framework (gameboard)

110 Building Blocks (BBs) i.e. tools, incentives, resources and practices used during development

3 Case Scenarios

Use of building blocks across the different phases and milestonesof drug development

Roadmap & Check-lists of “what to do” and “when to do it”

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Product discovery

Human PoC

Pivotal data

MAA / NDA / BLA

FIH ready

Patient care

Nonclinical PoP

Target

Idea

Repurposing

Line extension

Patient’sNEED

Additional authorization

Reimbursement

HTA assessment

First authorization

Disease knowledge

ODDG - FRAMEWORK

Patient’sNEED

Nonclinical PoP

Human PoC

Pivotal dataFIH ready Patient

careDisease

knowledgeMarket AccessTarget Product

discoveryMAA

NDA/BLA

NOT SUITABLE FOR THE DEVELOPMENTOF MEDICAL DEVICES

DOES NOT TAKE INTO CONSIDERATIONREPURPOSING AND LINE EXTENSION

LESS SPONSOR CENTRIC ANDMORE STAKEHOLDER CENTRIC

POST-APPROVAL PHASES HAVE BEENGROUPED AS MARKET ACCESS

Market Access

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ODDG – BUILDING BLOCKS (BBS) CLASSIFICATION

110 BBs were identified consisting of:

• Regulatory - pathways, designations and incentives for ODD in EU, US andJapan

• HTA and reimbursement - practices and procedures to support the economicvalue proposition and assessment, mainly focused on EU

• Early access - programs to enable patient treatment before regulatory licenseor local approval, either reimbursed or provided at no cost, according to thelocal regulation and practices

• Development practices - best-practice established by developers in the field ofrare diseases, to improve orphan drug development in terms of speed, qualityor efficiency

• Development resources - physical or practical existing accessible resource, tosupport drug developers in the orphan space

For each BB it was created a factsheet describing its relevance to rare disease drug development, availability, scope of use, output, pros and cons of usage, best time to apply, duration and costs.

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15%

25%

6%4%

50%

Development practices

Development resources

Early access

HTA and reimbursement

Regulatory

ODDG – CASE STUDIES

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Traditional, well-understood pharmaceutical (small molecule or a protein)

Available considerable body of knowledge around the disease in the regulatory and medical community

Patient population sufficiently understood and nonclinical development possible

Disease present in children and adults

LESS UNDERSTOOD DISEASESLESS UNDERSTOOD TECHNOLOGIES

Standard Orphan Drug Advanced Therapy

Development of novel platforms: Gene Therapy, Stem Cell Therapy, and Gene Editing

Available considerable body of knowledge around the disease in the regulatory and medical community

Patient population sufficiently understood and nonclinical development possible

Disease present in children and adults

Disregarded Disease

Prevalence is < 1 per-million inhabitants

Few knowledge on the disease

Natural history of the disease is little known; no severity or prognostic phenotypes have been identified so far

The disease exists only in pediatric patients

No biomarkers or clinically-relevant endpoints

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CAB’s

ERNs

AVAILABLE INFORMATION ON THE DISEASESTAKEHOLDERS MAPPING TARGET PATIENT VALUE PROFILE

Biomarkers

Diagnostic Tools

Natural History Studies

CRNs

c4c

AMED-IRUD

PCOMs

FINANCIAL RESOURCES

Public Funding

Private Funding

Coding of Rare Diseases

START

Are there patient organizations?

Are there community advisory boards?

Are there stakeholder networks?

Are there general development supportplatforms and infrastructures ?

EJP

Development Landscape analysis/ Horizon Scanning

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KEY TAKE AWAYS:• Missing info on the disease need to be generated ASAP• If not pre-existing, a solid stakeholder network has to be created• Stakeholder engagement is a constant activity throughout development

ODDG – REGULATORY & ACCESSPatient’sNEED

Nonclinical PoP

Human PoC

Pivotal dataFIH ready Patient

careDisease

knowledgeMarket AccessTarget Product

discoveryMAA

NDA/BLA

STANDARD ORPHAN DRUG

ADVANCED THERAPY

DISREGARDED DISEASE

Very Early Interaction

ODD

EU Regulatory Interaction

EMA-PA

ATMPs Certification

ATMPs Classification

EMA Qual. NovelMethodologies

NMSSA

PIP

EMA-FDA Regulatory Interaction

Par. EMA-FDA SA

US Regulatory Interaction

FDA SPARMAT

RegulatoryAccelerated

Programs

FDA – FTD

FDA - PR

CMA and FDA - AA

>>>>>>>>>>>>>>>>AACTARP >>>>>>>>>>>>>>>

PRIME >>>

Patient and market access

Compassion Programs >>>>>>>>>>>>>>

HTA adv.

HP-HE

J EMA-HTA SANSA w/ HTA

MoCAEUnetHTAEU CUP

US EAJ CUP

SPNP-RTU/ATU

J-ODD US-ODDEU-ODD

>>>>

Tim

ewin

dow

to a

pply

Star

t pre

parin

gfo

rBe

st ti

me

to a

pply

Skip

thro

ugh

SAKIGAKE

Regulatory Science Consultations

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INTERACTITF

EMA-SME

FDA Drug Dev. Qual. tool

>>>>>>>>>>>>>>>>

JP Regulatory Interaction >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>U and OL

FDA – BTD

CEASD >>>>>>>>>>>>>>>

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ORPHAN DRUG DEVELOPMENT GUIDEBOOK – FREELYACCESSIBLE ON IRDIRC WEBSITE

Including a video tutorial & an interactive

website

HOW TO USE THE ORPHAN DRUG DEVELOPMENTGUIDEBOOK IN YOUR OWN SETTING• The materials produced and displayed onto the interactive website can serve different

purposes:

• Expert platform resource: from accessing information on a single Building Block to gaining knowledge on the RD therapeutic development landscape as a whole

• Educational purposes: the content and the Gameboard/framework can be used for trainings

• Strategic development planning: the Gameboard/framework and the Building Blocks can be used to elicit a real case scenario for reflecting on a real development plan

• Long term sustainability ensured by transitioning of the ODDG to EJP-RD ‘Innovation & Clinical Trials Support’

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