UMCN, June 2012

Essentials for rapid and cost‐effective product developmentDr. Ronald van der Geest

The Long Road to a New Medicine...

Registration

Discovery

NDA/MMA

Full Development

Exploratory Development

Project Team and Plans

Synthesis of Compounds Screening

Early Safety Studies

Formulations Developed

Studies in Healthy Volunteers (Phase I)

Studies in 100‐300 Patients (Phase II)

Candidate Medicine Tested in 3‐10,000 Patients (Phase III)

Clinical Data Analysis

Large Amounts of Candidate Medicine 

SynthesizedExtensive Safety Studies

Candidate

Creating added value

3 Dimensions: time, cost & risk

How to get there?

The essentials:

IP

ExpertiseCapital

Capital

• Sufficient funding– Simple rule of thumb: 2‐3M projects get into trouble, 6‐8M projects don’t

• Based on a thought‐trough development plan– Include scenario’s 

– Plan for the best

– Ask funding for the worst

– It’s about managing expectations of shareholders

Expertisedevelopment/business plan

• Sufficient detail for all aspects tox, CMC, clinical, regulatory, etc.

• P&R… as much as possible

• CRO‐shopping: – We have seen anything in the range of 70k to 1.5M

Expertisedevelopment/business plan

Development plans compared…

Program I (1996) Program II (2002) Program III (2008)

4 phase I trials1 phase II trial2 phase III trials

2 open label trials

6 phase I trials0 phase II trials2 phase III trials

2 phase I trials1 phase II trial

development duration:

Est. 5‐6 yrs

development duration:

Est. 4 yrs

development duration:

Est. 2 yrs

Est. budget:

105 M

Est. budget:

60 M

Budget:

15 M

Organisation

CEO

Development management board

Core developmentteam

Sub teams

Collaborative teams

….

Protocol review committee

Organisation II

Very  limitedin‐house staff

CRO CROCROCRO CRO

Consultant

Consultant

Consultant

Consultant

Organisation III

BOD/Investors

MT SAB

Legal counsel

administration

CROSMO

PROJECT TEAM

The project team...

Who need to be in?

Management/Planning

Clinical operations

Non-clinical/Toxicology

CMC

Regulatory affairs

The project team...

• Core team staffing as early as possible 

‐ completeness

‐ availability

‐ continuity within the team

‐ full alignment with the company goals

‐ allow flexibility within the team

The project team…

• High level of ownership

• Fast and efficient

• Focus on high‐risk development

• Biggest risks:‐ running out of money‐ lack skills / over‐confident‐ too limited number of projects / risk of failure

Getting started

• Sorting out the regulatory process

• Scientific advice– “We are going to have a chat with FDA”

– “Rubbish‐in – rubbish‐out” principle

– Based on a solid plan

– Role play

– Negotiate

– Regulators are not the experts

The regulatory process

NCE no/yes

BE/hybrid application

BE study development implications &  

design

Hybrid study development implications & 

design

Full package

The regulatory process

Scientific advice – 2 example questions:

“It is the sponsor’s position that the completed nonclinical safety studies are adequate to support a MAA in the proposed indication.  Does the Agency concur with the sponsor’s position?”

“Does the Agency agree that the proposed program of clinical pharmacology studies is adequate and is sufficient to support a MAA in the targeted indication?” 

PKPD modeling implementation

16 subjects

2.5 mg IV  + placebo 

5.0 mg + placebo 

IV

Placebo + placebo 

IV

2.5 mg  + placebo 

IV

4-way cross-over, double blind, placebo controlled

PKPD modeling implementation

Clinical Utility Index Balancing Efficacy  and Safety in Drug Development Decision Making

Maidstone 48A, 5026 SK Tilburg Tel: +31 (0)13 534 8272Website:www.3d‐pxc.com

Contact details

Ronald van der Geest, PhDPartner & General Manager+31 6 523 901 30Ronald@3d‐pxc.com

Molenweg 50, 5349 AC OssTel: +31 (0)6 55 71 86 66Website:www.3d‐pxc.com

The Long Road to a New Medicine...

Questions?