CPTR 2012 WORKSHOP

Dr. Wim Parys: Head Infectious Diseases Unit

Cross-Sector Perspectives: Industry October 3, 2012

Agenda

• Industry perspective on challenges in TB drug development – Finance: ROI and justification needed within companies to invest

in these programs– Clinical Trial: conducting trials mostly in developing countries– Regulatory challenges: lack of harmonization– Post market arena: how to assure appropriate use – Supply chain: getting secure drug supply into HBC’s

• Industry perspective on opportunities– Where has progress been made?

• What would ease the burden for developing TB treatments – Incentives, include AMC’s and other innovative solutions

206.03.2010To edit footers: "insert tab>header and footer" and apply to all

Top Challenges in TB Drug development: Overview

Clinical trial related - Clinical trial capacity in HBCs- Need for Capacity building- Limited lab capacity- Long timelines TB efficacy trials / cost impact- Scarcity of surrogate markers- Scarcity of good companion drugs

Regulatory hurdles- Clinical trial approval timelines- Lack of regulatory harmonization or fast track for public health related solutions- Need to address single agent approval process- Long regulatory timelines and expense

Adoption- WHO process for updating treatment guidelines- Essential medicines list- Prequalification process- National TB program hurdles

Lack of commercial incentives

- Limits drug development and drug discovery- Limits scale of manufacturing (small volumes = higher prices)

3

Industry Challenges

Long Development timeline, even for a lean program

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Non-Clinical

11 trials

C20275 pts

C208 Stage 1 47 MDR-TB pts

C209, 233 MDR, pre-XDR, XDR-TB pts

Phase II

Phase I

Phase III C210, ~600 MDR ,

pre-XDR-TB pts

Non Clinical

C208 Stage 2,160 MDR-TB pts

Privileged and Confidential

Phase III timeline based on traditional endpoints (treatment free cure) as per FDA requirements

Challenging Geography and Financials

Privileged and Confidential

Returns Costs

PAC’s = Post approval Commitments

MDR-TB Estimated Cases2010

Source: WHO 2011N = ~ 650,000

US EU India, S. Africa China

Russia

TMC207: Challenging Geography; Long regulatory timelines

High Burden Countries

2012 2013 2014 2015Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

RegulatoryApprovals estimated

Long timelines

No Janss

en presence(37)

Top 50 Countries

Privileged and Confidential

Further regulatory priorities will be developed for the remaining 23 high burden countries: Process to be repeated on a country by country basis

Ensuring appropriate use and supply chain?Global Source of 2nd line MDR TB DrugsDealing with small volumes + 40k treatments/year globally

*GDF orders for 2009-2010. Many drugs ordered in 2009 were not delivered until 2010.

GDF65%Oth

er25%

NGO10%

Global MDR Treatments- 2010

*GDF procurement agency for TB drugs

How well is it working???Privileged and Confidential

Not-For-Profit Supplier of TB, HIV Drugs *

• Hope in changing an antiquated,

cumbersome, treatment paradigm• On June 29, 2012, Janssen submitted a

New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for bedaquiline (TMC207), as part of combination therapy for pulmonary multi-drug resistant tuberculosis (MDR-TB). This is the first NDA to seek an indication for MDR-TB. Priority review has been granted

• On August 31, 2012, Janssen announced submission of a Marketing Authorisation Application to the European Medicines Agency (EMA) seeking conditional approval for bedaquiline (TMC207), to be used as part of combination therapy for pulmonary, multi-drug resistant tuberculosis (MDR-TB) in adults.

Opportunities: Where has progress been made?

45 years since the introduction of the world’s last TB drug

Privileged and Confidential

Photo courtesy of James Nachtwey

How did we make it work?

10

Part of Janssen’s mission is to ensure that its portfolio of HIV/TB medicine is accessible to patients in developing countries.

Access issues in developing countries are complex and are made difficult by the lack of infrastructure, education, funding, trained medical professionals, and local government commitment.

Janssen is also committed to furthering healthcare access in developing countries. Examples include:• Voluntary licensing for local manufacturing for certain diseases of the developing world • Broad access programmes for diseases such as HIV/AIDS on a cost recovery basis in

least developed countries and lower tier pricing for countries with developing economies• Early access programmes –(prior to drug approval and) administered under controlled

conditions • Product donation programmes and other philanthropic efforts to address basic

healthcare infrastructure needs where needed. • “Children without worms” provides 400million doses of mebendazole in support of global eradication efforts.

Innovative financing mechanisms – e.g. Advance Market Commitments – Forward purchase agreements with numbers-of-patient laden

incentives, etc.

What would ease the burden for developing TB treatments: Better incentives

Privileged and Confidential

Regulatory harmonization/mutual recognition

Validated surrogate markers … Speeding up clinical trial testing and/or adaptive clinical trial design even in support of traditional approval

Thank you

Janssen-Infectious Diseases BVBA