October 3, 2012
Arlington, VA
Otsuka Global TB Program Updates
CPTR Workshop
TB innovation for tomorrow.
Overview
— Challenges in TB Drug Development
— Recent Publications/Presentations
— NEJM Results from Trial 204
— ERJ Report on long-term follow-up
— IAS and ICAAC DDI studies with anti-retroviral drugs
— Ongoing Phase III Trial
— Responsible Access
— Public Health Advocacy, Awareness and Education
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New TB Drugs Overcome Modern RA Hurdles
New TB
Drug?
High
Thorough QTc
ICH-GMP
DDI (CYP)
ICH-GCP
GLP (OECD)
ICH created
IRB (FDA)*
Belmont Report (FDA)**
GMP/GLP (FDA)
RFP
1967
Prospective Statistics
1972
1978 1979 1981
RFP: Rifampicin (FDA approval)
DDI: Drug-drug interaction
ICH: International Conference on Harmonization
* US-FDA adopted IRB based on Declaration of Helsinki
1990 1992
1996 1997 1999
GCP: Good Clinical Practice
GMP: Good Manufacturing Practice
GLP: Good Laboratory Practice
**Ethical guidelines for clinical research
2005 Today
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Otsuka’s Studies of Delamanid to Provide 6-months
of Treatment and 24 Month Follow-up
Trial 116
Trial 204
Delamanid
OBR
2 mo
Trial 208 with varying time of entry for 6 month exposure
Intensive Phase
Continuation Phase
Long-Term Outcome
at 24 mo
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Phase II Results Demonstrate Long- and ShortTerm Efficacy of Delamanid
Short-Term Efficacy
— As reported in the New England Journal of Medicine (NEJM), results from Trial 204
demonstrate treatment with delamanid + OBR led to 53% increase in SCC compared to
placebo + OBR
— If SCC achieved within first 2 months, patients have considerably higher likelihood of
successful treatment outcome
Long-Term Efficacy
— As reported in the European Respiratory Journal (ERJ), combined analysis of Trials
204/208/116 shows
— Among all patients (N=421) 74.5% achieve favorable outcome with DLM >6mo
delamanid vs. 55.0% with <2mo (1% mortality in patients receiving DLM ≥ 6mo
vs. 8.3% ≤ 2mo)
— Among all patients (N=421) 1% mortality in patients receiving DLM ≥ 6mo vs.
8.3% ≤ 2mo
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Safety Results Demonstrate Delamanid was
Well-Tolerated Among Study Subjects
— Most AEs within mild to
moderate range and
balanced among delamanid
and placebo groups;
consistent with OBR
— Higher incidence of QTcF prolongation, which did not result in any
clinical manifestations
— As reported at International AIDS and ICAAC 2012 Conferences, DDI
studies in healthy subjects show no significant interactions when
delamanid co-administered with tenofavir, efavirenz or Kaletra
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Given Encouraging Results, Launch of Phase III
(Trial 213)
N = ~300
MDR TB
Culture +
Patients
OBR +
Delamanid
100 mg BID
(n1 = 200)
OBR +
Placebo
(n2 = 100)
2 months:
•SCC
•Clinical Δ
+4 months:
•SCC
•Clinical Δ
•Time to SCC*
+12-18 mos:
•Rx outcomes
+6-12 mos:
Relapse
• Total duration – 30 mos.
• Total enrollment – 400 patients sputum culture positive for
MDR-TB
• Stratification – HIV+ (S Africa); bilateral cavities on CXR
• Co-primary endpoints
SCC – @ 2 months
Time to SCC over 6 months
• Enrolling in Estonia, Latvia, Lithuania, Peru, Philippines, and
South Africa. Adding Moldova and India soon.
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Committed to the Rational Use of Delamanid –
Responsible Access Plan (RAP)
Professional Education
— Medical education program targeting physicians and patients
— Focus topics such as diagnostic options, timely and accurate SAW
reporting, background on development of drug resistance, among
others
Comprehensive Registry
—A multi-center, EU-wide post-authorization study to assess the
safety and drug usage of Delamanid in MDR-TB patients
Strict Distribution Control
— All orders routed through single distributor using web-based tool
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Otsuka’s Commitment to Improving Patient Care
— Support and/or develop approaches to
excellence in TB case management
(Moldova)
— Explore models of patient support
leading to individual and community
socio-economic improvement
— Advocate for sustained international commitment and response
to the TB crisis from funders and policymakers
— Increase public awareness of TB as a universal health issue
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Making an Impact – One Patient at a Time
Mildred Fernando
— Battled TB for a total of 10 years,
since age 19
— Diagnosed twice with XDR-TB,
received two, 18 month courses of
treatment
— Father died of TB, two sisters
diagnosed and survived
— Mildred participated in delamanid RCT and open-label study
— Today she is living TB-free and works at the Lung Center of the Philippines,
helping other TB patients. She is also a strong patient-advocate for the WHO and
other international organizations
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Otsuka’s Commitment to TB Education,
Awareness & Advocacy
− To capture stories like Mildred’s,
photo magazine created with
TB/MDR-TB life stories
(Estonia, Philippines, Peru)
− Collaboration with European
Respiratory Society (ERS)
− Aimed at illustrating MDR-TB as a
potentially treatable and
winnable disease, providing hope
and encouragement to other
patients
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Conclusion
— Global TB Program a long-term investment by Otsuka
— New compound represents only a first step in a
comprehensive disease management package that aims to
FighTBack against TB from all angles (diagnostics, pediatrics,
public health, etc.)
— Actively working with global TB stakeholders and other thirdparties with mutual goals of addressing unmet medical needs
in TB while promoting rational use of new compounds and
minimizing resistance
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