October 3, 2012
Arlington, VA
Otsuka Global TB Program Updates
CPTR Workshop
TB innovation for tomorrow.
— 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
Proprietary and Confidential
New TB Drugs Overcome Modern RA Hurdles
New TB
Thorough QTc
ICH created
Belmont Report (FDA)**
Prospective Statistics
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
Proprietary and Confidential
Otsuka’s Studies of Delamanid to Provide 6-months
of Treatment and 24 Month Follow-up
Trial 116
Trial 204
2 mo
Trial 208 with varying time of entry for 6 month exposure
Intensive Phase
Continuation Phase
Long-Term Outcome
at 24 mo
Proprietary and Confidential
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
Proprietary and Confidential
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
Proprietary and Confidential
Given Encouraging Results, Launch of Phase III
(Trial 213)
N = ~300
Culture +
100 mg BID
(n1 = 200)
(n2 = 100)
2 months:
•Clinical Δ
+4 months:
•Clinical Δ
•Time to SCC*
+12-18 mos:
•Rx outcomes
+6-12 mos:
• Total duration – 30 mos.
• Total enrollment – 400 patients sputum culture positive for
• 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.
Proprietary and Confidential
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
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
Proprietary and Confidential
Otsuka’s Commitment to Improving Patient Care
— Support and/or develop approaches to
excellence in TB case management
— 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
Proprietary and Confidential
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
— 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
Proprietary and Confidential
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
Proprietary and Confidential
— 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
Proprietary and Confidential

similar documents