Transcript WTBD2004 35 The future of Drug development - Maria Freire

Working Group
on TB Drugs
Developing A Faster Cure
Maria C. Freire, Ph.D.
Chair
Working Group Coordination
Treatment Today
Treatment Tomorrow
DOTS-Plus
MDR-TB
HIV/TB
New
TB Vaccines
DOTS
Expansion
New TB
Drugs
New
TB Diagnostics
Mission
To deliver faster and affordable
TB medicines that will be the
cornerstone of tomorrow’s TB
control.
WG Membership
ABPI • ALA • Alkem • Astrazeneca • ATS • Aventis •
Bayer • Case Western • CDC • Denver Health &
Hospitals • DFID-UK • Faculte de Medicine PitieSalpetriere • FDA • Gates Foundation • GATB •
GlaxoSmithKline • Global Forum for Health Research
• Hikal Ltd. • EU Research Directorate • IUATLD •
JATA • Johns Hopkins • KNCV • Kyoto
Pharmaceutical Univ. • Lupin Ltd. • MSF • MRC • NIH
• NIPER • Novartis • Partners in Health • Pfizer •
Rockefeller Foundation • RTI • TDR • Sequella • St.
George’s Hospital Medical School • Stop TB •
Tuberculosis Research Center-Chennai • University
of Natal • University of Rio de Janeiro • USAID •
Wanchai Chest Clinic • WHO • The World Bank
New Drug Profile
• Simplify or shorten TB treatment to 2
months or less
• Be effective against MDR-TB
• Shorten/improve latent TB treatment
• Easily adopted in the field
Drug Development Pipeline
Basic
Research
Discovery
PreClinical
Gap
Phase
I
Phase
II
Phase
III
Registration
& Post
Clinical
Technology Mapping
• Goal:
– Assess TB drug development landscape within
WG
• Process:
– Formed Subcommittee of Core Group
– Surveyed 60 WG Members, 25 responded
• Results:
– Discussion of preliminary data
– Evaluation of information
Mapping Exercise
Basic
Research
Compounds
Technology
Platforms
Capacity
Building
Discovery
Lead
Identification
&
Optimization
Preclinical
Clinical
Trials
Regulatory
Mapping Results to Date
By Project
Compounds
Technology
Platforms
Capacity
Building
Basic
Research
Discovery
Lead
Identification
&
Optimization
Preclinical
Clinical
Trials
●●●●
●●●●
●●●
●●●
●●●●●●
●●●●●●
●●●
●●●
●●●●●●
●●●●●
●●
●●●
●●●
●●
●●
●●●
●●●
●●●●
Regulatory
●
Mapping Results to Date
By Project
Compounds
Technology
Platforms
Capacity
Building
Basic
Research
Discovery
Lead
Identification
&
Optimization
Preclinical
Clinical
Trials
●●●●
●●●●
●●●
●●●
●●●●●●
●●●●●●
●●●
●●●
●●●●●●
●●●●●
●●
●●●
●●●
●●
●●
●●●
●●●
●●●●
Regulatory
●
pt
im
io
n
iz
at
ec
l in
ic
al
O
Cl
in
ic
al
Pr
Le
ad
0
ic
at
io
n
y
es
ea
rc
h
is
co
ve
r
R
Id
en
tif
D
as
ic
Le
ad
B
Mapping Results to Date
(by project)
12
10
8
6
4
2
WG Portfolio Data
Lead
Lead
Identification Optimization
Pyridones
and Quinolizines
PA-824
Analogs
Compounds
Thiolactomycin
Ascididemin
Compounds
Third Generation
Macrolides
Pre-Clinical
PA824
LL-3858
(Pyrroles)
Clinical
Moxifloxacin
Rifapentine
KRQ 10018
Rifabutin
PA 20013
Capreomycin
Ethambutol
Analogs
Gatifloxacin
MJH 98-I-81
& Analogs
Rifalazil
Analogs
Levofloxacin
Anti-Persisters
Linezolid
Ofloxacin
Non-profit Project
Industry
Project
TB
Alliance
Project
Combination Project
Late
Discovery
Preclinical
Phase I
Phase II
Phase III
Portfolio
Management
Lead identification
and optimization
----------------------------Clinical Trials-------------Pre-clinical
Development
Contracts
and IP Management
for Equitable Access
Accelerate Discovery
Streamline
Development
Ensure Prompt
Registration & Field Transfer
Scaling Up R&D Activities
ar
e
Y
1
ar
Ye
2
ar
e
Y
3
ar
e
Y
4
ar
e
Y
5
ar
Ye
6
ar
e
Y
7
ar
e
Y
8
ar
e
Y
9
ar
e
Y
10
Case Studies
PA-824
“[This] deal tells me … that biotech leaders,
international health officials and philanthropic
groups are trying to create mechanisms to
address needs that would otherwise fall
through the cracks. I’m keeping my fingers
crossed, both for the TB drug and the larger
experiment in non-profit drug development.”
O2N
N
O
N
Tom Abate, Biotech columnist,
San Francisco Chronicle.
F
O
F
O
F
PA-824 Development Schedule
Drug Development Outsourcing Network
Under Evaluation:
Peru
Russia
India
South Africa
Brazil
Existing Sites
Moxifloxacin
1st Results from MXF Studies
Log CFU in entire lung
Lung CFU counts
10
9
8
7
6
5
4
3
2
1
0
Untreated
2RHZ+4RH
2RHZM+4RHM
2RHM+4RH
2RMZ+4RM
2MHZ+4MH
0
1
2
3
4
5
6
Duration of treatment (mos.)
Moxifloxacin Murine Model Results of log10 CFU counts from lung homogenates. (Jacques
Grosset & William Bishai - JHU)
Clinical Trials
Moxifloxacin
Phase II
– Johns Hopkins U & Brazil (FDA Orphan
Drug Office)
– CDC TBTC Study 27
– TRC Chennai
Special Considerations
•
•
•
•
AAA strategy: Affordability, adoption, access.
Strategic IPR Provisions
Ensure endemic country participation early on
Build-in provisions for technology transfer and
support for production in developing countries.
+
+
Conclusions
•
•
•
•
•
First TB pipeline in 40 years
World-wide participation in WG activities
New TB Drugs will revolutionize DOTS
Must ensure sustainability
The time to act is NOW!