TB Drug Co-Development Roundtable: SIRTURO® (bedaquiline)

Myriam Haxaire: Compound Development Team Leader, Janssen Global Public Health

CPTR meeting Oct 03, 2013

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Bedaquiline Development Plan

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

Non-Clinical

11 trials

C202 75 pts

C208 Stage 1 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, MDR-TB pts

www.sirturo.com

•USA: Approval Dec 28, 2012

•WHO Interim guidance: June 13, 2013

•Filings pending:

– EMA: filed August 31, 2012

– China: October 30, 2012

– South Africa: December 6, 2012

– Thailand March 29, 2013

– Russia (partner): April 16, 2013

– India: May 10, 2013

– Vietnam: August 2, 2013

Current status

June 13, 2013: WHO interim policy guidance

•WHO recommends that bedaquiline may be added to a WHO-recommended regimen in adult patients with pulmonary MDR-TB when 5 conditions are met:

1. Treatment under closely monitored conditions

2. Proper patient selection

3. Patient informed consent

4. Treatment design based on WHO recommendations • (DST): Z + 4 drugs considered effective

• FQ or SLD resistance

• AE’s, poor tolerance, or contraindication

• XDR TB (with or instead of Group 5 drugs)

5. Pharmacovigilance

Evidence used

•Efficacy

•Safety: evaluation of AE’s of interest, CVS, Hepatic safety

•Evaluated the balance between harms and benefits, Cost-effectiveness

More Effective

Treatment

Improved Safety /

Tolerability

Shortening Treatment Duration

Simplified Regimens

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Objectives for Development of

New MDR-TB Therapy

Phase III Study (C210): double blind, randomized,

superiority design

Is this the best path forward? (8 drug- 9m regimen)

BR + BDQ

Treatment

Phase

Follow-up

Phase

BR + placebo

Treatment-free FU*

Treatment-free FU*

36 weeks 48 weeks

Primary efficacy analysis and unblinding at Week 60

1:1

BR = KPrHLECZ (6m) + LECZ (3m)

Secondary endpoint: relapse-free cure at Week 84

*All patients will also have survival follow-up for two years post last blinded study drug dose

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Ongoing initiatives in the field: STREAM

• Comparative trial: 9m Bangladesh regimen vs

WHO SOC

• N = 400 (randomized 2:1)

• Trial is ongoing

• Potential collaboration is under discussion

• possible study arms include a regimen

shortening/simplification and an all-oral regimen

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Janssen US Registry: background

• A post marketing requirement relative to the accelerated approval of BDQ by the FDA (PMR-002)

• Main Objectives: Describe adverse events among BDQ-treated patients, including deaths

Describe patient outcomes (clinical and microbiologic)

Describe the medical indication and utilization of expert medical consultation

among patients treated with BDQ

• Unique opportunity for a Janssen Administered Global MDR TB Registry with a SOC cohort, building on the existing US registry protocol in coordination with WHO policy implementation package – Operational research to ensure many more patients receive BDQ over

the next 2-3 years with high quality patient outcome data

– Public-private partnership for active pharmacovigilance

– Longitudinal follow-up of patient survival

• Change an antiquated, cumbersome, treatment paradigm

• Contribute to the realization of global ambitions to eradicate TB by 2050

• Forge a sustainable model(s) to develop medicines that address neglected diseases

• Partner with the public sector to pool resources and move the TB field forward

We hope to…

Photo courtesy of James Nachtwey

Thank you!

Questions?