tb drug co-development roundtable: sirturo® (bedaquiline) · june 13, 2013: who interim policy...
TRANSCRIPT
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?