TB innovation for tomorrow. Delamanid: A New Treatment for MDR Delamanid: A New Treatment for MDR - - TB TB XVIII International TB Workshop. UITB XVIII International TB Workshop. UITB - - 2014 2014 45 45 th th Union World Conference on Lung Health Union World Conference on Lung Health 29 October, Barcelona, Spain PROPRIETARY AND CONFIDENTIAL
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Delamanid: A New Treatment for MDR -TB · Overview of MDR-TB Treatment Trials for Delamanid Trial 204 RCT of safety, efficacy, and PK of delamanid or placebo in combination with OBR
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TB innovation for tomorrow.
Delamanid: A New Treatment for MDRDelamanid: A New Treatment for MDR--TBTBXVIII International TB Workshop. UITBXVIII International TB Workshop. UITB--2014 2014
4545thth Union World Conference on Lung HealthUnion World Conference on Lung Health
29 October, Barcelona, Spain
PROPRIETARY AND
CONFIDENTIAL
Proprietary and Confidential
2
Overview
• Background
• Review of Delamanid Phase 2B Program
• Ongoing Delamanid Phase 3 Trial
• Delamanid Paediatric Program
Proprietary and Confidential
Background
• Otsuka searching for new treatment options for TB for > 30 years
• Delamanid (Deltyba†) discovered in house in 2002 with first-in-man testing in 2004
• Delamanid 14-day EBA trial conducted in 2006
‒ Treatment effect approximately that of rifampicin
‒ Determined exposure range/dose required for efficacy
• MDR-TB program designed in 2007; first trial launched in 2008
• Phase 3 confirmatory trial launched September 2011
• Registration
‒ European Medicines Agency, April 2014
‒ PMDA (Japan), July 2014
†Currently authorized for marketing in U.K, Germany, Japan
Proprietary and Confidential
Delamanid has Novel Mechanism of Action and
No Cross Resistance to Existing Anti-TB Drugs
Nitro-dihydro-imidazooxazole derivative
Mechanism of Action: Inhibition of key mycolic acid synthesis
‒ Largely outpatient with DOT plans for all patients
�Trial 116
�Vital status
‒ Observational study of Trial 204 patients up to 2 years after Rx initiation to assess sustainability of SCC and final treatment outcomes; 87.5% assessed
‒ on 464/481 (96.5%) at ≥ 24 months
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Proprietary and Confidential8
Trial 204 Primary Efficacy Endpoint†
SCC using liquid media (MGIT) at 2 months
0
20
30
40
50
OBR + PlaceboOBR + Delamanid
100mg BID
29.6 %
45.4 %
p=0.008
p=0.039
200mg BID
41.9 %
(57/136)
(64/141)
(37/125)
Treatment with Delamanid →→→→ ~50% increase in SCC at 2 months
†Gler, et al. NEJM, June 2012
% P
atie
nts w
ith S
CC
Proprietary and Confidential9
Consistency in Primary & Secondary Analyses Demonstrates Robustness of Efficacy Results
SCC = sputum culture conversion
TTD = time to detection in MGIT system (bacterial load)
Proprietary and Confidential
Trial 204: 2-month SCC among XDR-TB Patients
Proprietary and Confidential
Summary of Safety Findings for Trial 204†‡
� Hospital-based treatment period
� Daily assessment of AEs
� Weekly assessment of clinical laboratory parameters
� Frequent ECG monitoring
� > 400 AEs reported by at least 1 patient†
‒ Balanced across three treatment groups
‒ Type/frequency of AEs consistent with reports for OBR
� Increased AEs of QT interval prolongation based on ECG assessments by investigators; none coupled with clinical manifestations
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†Gler, et al, NEJM 2012
‡Summary of Medical Product Characteristics, 2014: