Cross-Sector Perspectives: Global Health Christian Lienhardt Stop TB Department CPTR Workshop...
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Transcript of Cross-Sector Perspectives: Global Health Christian Lienhardt Stop TB Department CPTR Workshop...
Cross-Sector Perspectives: Global Health
Christian LienhardtStop TB Department
CPTR WorkshopOctober 2-4, 2012
Overview of the presentation
• Background – Global TB burden
• Challenges in introducing new TB drugs/regimens
• Developing Guidance to countries
• A pluri-partners model
Overview of the presentation
• Background – Global TB burden
• Challenges in introducing new TB drugs/regimens
• Developing Guidance to countries
• A pluri-partners model
Estimated number of
cases
Estimated number of
deaths
1.4 million(range: 1.2–1.6 million)
8.8 million(range: 8.5–9.2 million)
440,000(range: 390,000–510,000)
All forms of TB
Multidrug-resistant TB (MDR-TB)
HIV-associated TB
1.1 million (13%) (range: 1.0–1.2 million)
350,000(range: 320,000–390,000)
The Global Burden of TB -2010
about 150,000
Estimated TB incidence rates, by country, 2010
TB cases per 100 000
0–24
25–49
50–99
100–299
>=300
No estimate
Estimated TB incidence rates, by country, 2010
TB cases per 100 000
0–24
25–49
50–99
100–299
>=300
No estimate
TB Incidence Rates - 2010
Estimated TB incidence rates, by country, 2010
TB cases per 100 000
0–24
25–49
50–99
100–299
>=300
No estimate
Eastern Mediterranean7%
South-East Asia40%
Western Pacific 19%
Africa 26%
Americas 5%Europe 5%
• Highest burden in Asia (59% of 8.8 million cases)
• Highest rates in Africa, due to high HIV infection rate
~80% of HIV+ TB cases in Africa
Impact of HIV on TB in Africa
Notified cases per 100,000 pop. 1980-2008
Percentage of global estimated HIV-positive TB cases
EMR
Cameroon
Thailand
Brazil
Democratic Republic of the Congo
China
Myanmar
EUR
Côte d'Ivoire
Malawi
United Republic of Tanzania
AMR
Zambia
WPR
Ethiopia
Mozambique
Kenya
Uganda
Zimbabwe
Nigeria
India
SEA
South Africa
AFR
1% 5% 10% 20% 50% 90% 0
100
200
300
400
500
600
700
1980 1984 1988 1992 1996 2000 2004 2008
Botswana
Côte d'Ivoire
DR Congo
Gabon
Guinea
Kenya
Malawi
Mozambique
South Africa
UR Tanzania
Zimbabwe
• 80% of all TB/HIV cases world-wide are in Africa• 50% of all TB/HIV cases world-wide in 9 African countries• 23% of the estimated 2 million HIV deaths due to TB
% MDR-TB among new TB cases,1994-2009
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on
maps represent approximate border lines for which there may not yet be full agreement. WHO 2010. All rights reserved
Australia, Democratic Republic of the Congo, Fiji, Guam, New Caledonia, Solomon Islands and Qatar reported data on combined new and previously treated cases.
0-<3
3-<6
6-<12
12-<18
>=18
No data available
Subnational data only
Notified cases of MDR-TB
Cases of MDR-TB
0–99
100–999
1000–9999
≥10 000
NA
Estimated absolute numbers of reported cases with MDR-TB*
Notified cases of MDR-TB
Cases of MDR-TB
0–99
100–999
1000–9999
≥10 000
NA*among reported pulmonary TB patients
<100100–999
1000–9999>10,000
13 top settings with highest % of MDR-TB among new cases, 2001-2010
16.5
19.2
19.3
19.4
20.0
22.3
23.8
27.3
28.3
15.4
14.8
16.0
16.1
0 5 10 15 20 25 30
Tashkent, Uzbekistan (2005)
Estonia (2008)
Donetsk Oblast, Ukraine (2006)
Mary El Republic, Russian Federation (2008)
Dushanbe city and Rudaki district, Tajikistan (2009)
Belgorod Oblast, Russian Federation (2008)
Kaliningrad Oblast, Russian Federation (2008)
Republic of Moldova (2006)
Ivanovo Oblast, Russian Federation (2008)
Baku city, Azerbaijan (2007)
Arkhangelsk Oblast, Russian Federation (2008)
Pskov Oblast, Russian Federation (2008)
Murmansk Oblast, Russian Federation (2008)
35.3Minsk, Belarus (2010)Preliminary results
Countries that had reported at least oneXDR-TB case by late 2011
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2011. All rights reserved
Argentina Bhutan France Japan Namibia Republic of Korea ThailandArmenia Cambodia Georgia Kazakhstan Nepal Republic of Moldova TogoAustralia Canada Germany Kenya Netherlands Romania TunisiaAustria Chile Greece Kyrgyzstan Norway Russian Federation UkraineAzerbaijan China India Latvia Pakistan Slovenia United Arab EmiratesBangladesh Colombia Indonesia Lesotho Peru South Africa United KingdomBelgium Czech Republic Iran (Islamic Rep. of) Lithuania Philippines Spain United States of AmericaBotswana Ecuador Ireland Mexico Poland Swaziland UzbekistanBrazil Egypt Israel Mozambique Portugal Sweden Viet NamBurkina Faso Estonia Italy Myanmar Qatar Tajikistan
2015: Goal 6: Combat HIV/AIDS, malaria and other diseases Target 6c: to have halted by 2015 and begun to reverse the
incidence…
*Indicator 6.9: incidence, prevalence and mortality associated with TB*Indicator 6.10: proportion of TB cases detected and cured under DOTS
2015: 50% reduction in TB prevalence and deaths by 20152050: elimination (<1 case per million population)
The Global TB Control Targets
Incidence, prevalence and mortality rates: global estimates
Peak in 2002
TargetTarget
Prevalence Mortality
150
100
50
0
Rat
e p
er 1
00,0
00 p
op
ula
tio
n
250
200
150
100
50
0
Incidence
25
20
15
10
5
0
1990 2010 1990 2015 1990 2015
40% decline since 1990Falling 1.4% per year
7.68.8
3.7
5.8
Global notifications (black) in context of estimated incidence (green)
TB
cas
es (
mil
lio
ns)
Estimated Global Case Detection
65% (63–68%)
Detection gap: 1/3
Treatment success 87% globally…but Europe lagging behind
Global, new sm+ WHO Regions, new sm+93
88
81
76
67
87
8584
86 86
83
80
76
78
80
82
84
86
88
Tre
atm
ent
succ
ess
rate
(%
)
65
70
75
80
85
90
95
Europe
Americas
Africa
EMR
SE Asia 89
W. Pacific
Notifications of MDR-TB increasing
BUT only ~ 1 in 5 (19%) of estimated cases of MDR-TB among reported TB patients diagnosed and treated in 2011
Notified cases of MDR-TB
0
10
20
30
40
50
60
2005 2006 2007 2008 2009 2010
Nu
mb
er
of
pa
tie
nts
(th
ou
sa
nd
s)
19,000
53,000
Global Plan target ~270,000 in 2015
0
50
100
150
200
250
300
SE Asi
a
W. P
acifi
c
Europe
Africa
EMR
Americ
as
World
Not on treatment
Treated
MDR-TB cases treated and estimated numbers not
treated for MDR-TB, among notified TB patients, 2010
290,000
Time trends in TB and MDR-TB: reverting, controlling, and alarming…
1
10
100
1000
1996 1998 2000 2002 2004 2006 2008
0.3% per year
19.4% per year
____ TB ____ MDR-TB
1
10
100
1999 2001 2003 2005 2007 2009
2.4% per year
-2.4% per year
____ TB ____ MDR-TB
1
10
100
1998 2000 2002 2004 2006 2008
-6.7% per year
-5.1% per year
____ TB ____ MDR-TB
Botswana
Tomsk Oblast, Russia
Estonia
Overview of the presentation
• Background – Global TB burden
• Challenges in introducing new TB drugs/regimens
• Developing Guidance to countries
• A pluri-partners model
Current TB Therapy and Unmet Needs
* Rifampin (R), Isoniazid (H), Pyrazinamide (Z), Ethambutol (E)
Patient Population Current Therapy Unmet Needs
Drug-SusceptibleDS-TB
4 drugs; 6 month therapy (2RHZE + 4RH) Shorter, simpler therapy
Drug-ResistantM(X)DR-TB
At least 4 drugs (including injectable); ≥18 months;poorly tolerated
Fully oral, shorter and safer therapy
TB/HIVco-Infection
Drug-drug interactions (DDI) with ARVs
No or low DDI, co-administration with ARVs
Latent TBInfection 6-9 months H Shorter, safer therapy
► For all indications and treatment, issues in delivery and access► Need shorter and simpler therapies against both DS and DR-TBAdapted from TB Alliance
Lead Optimization Preclinical Development
GLP Tox. Phase I Phase II Phase III
GatifloxacinMoxifloxacinRifapentineDelamanid (OPC67683)
Bedaquiline (TMC-207)PA-824LinezolidSQ-109RifapentineNovel Regimens2
PNU-100480
AZD5847CPZEN-45SQ641SQ609DC-159aQ201
Preclinical DevelopmentDiscovery1 Clinical Development
NitroimidazolesMycobacterial Gyrase InhibitorsRiminophenazinesDiarylquinolineTranslocase-1 InhibitorMGyrX1 inhibitorInhA InhibitorGyrB inhibitorLeuRS InhibitorPyrazinamide AnalogsSpectinamidesChemical classes: fluoroquinolone, rifamycin, oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone
1 Ongoing projects without a lead compound series can be viewed at http://www.newtbdrugs.org/pipeline-discovery.php2 Combination regimens: first clinical trial (NC001) of a novel TB drug regimen testing the three drug combination of PA-824, moxifloxacin, and pyrazinamide completed August 2011.
Global TB Drug Pipeline 2012
BTZ043
www.newtbdrugs.org
• Novel drugs and shortened treatment regimens with new and/or re-purposed drugs are proceeding along the clinical development pathway;
• New drugs submitted for regulatory approval for treatment of drug-resistant MDR-TB;
• Implications for TB control programmes:– determine optimal regimens for use of newly developed
and/or repurposed drugs for treatment of DS- and DR-TB under programmatic conditions;
– evaluate requirements for patients’ eligibility;– assess programmatic feasibility;– evaluate cost-effectiveness of newly-developed
treatments;– ensure proper surveillance and pharmacovigilance;– ensure responsible use (appropriate indication, doses,
drug combination(s), and treatment duration) – prevent off-label use and amplification of resistance;
Public health challenges of introduction of new TB drugs in countries
Overview of the presentation
• Background – Global TB burden
• Challenges in introducing new TB drugs/regimens
• Developing guidance to countries
• A pluri-partners model
STAG-TB recommendations for guidance on new drugs for TB (Sept 2010)
STAG-TB recommends that:
- WHO issues clear policies to guide countries on the introduction of new regimens for treatment of DS and DR-TB […] upon availability of evidence in support of use of such regimens;
- WHO issues specific requirements on what evidence and information would be needed to develop policy recommendations related to new drugs/regimens for treatment of DS and DR-TB;
- WHO promotes collaboration and action by partners [...], so that appropriate drug regimens are utilized by programmes for the treatment of DS- and DR-TB, inclusive of the new drugs, and avoid irrational use of new tools;
- WHO organizes expert consultation(s) to review the evidence for use of new drugs and regimens to inform timely development of treatment policy guidance to national health authorities.
Objectives:
• To advise and assist WHO Stop TB in the development and monitoring of a strategic plan to prepare WHO policy guidance for the rational introduction of new TB drugs/regimens in countries;
• To advise and assist in the development of a policy development framework for the introduction of new drugs/regimens for the treatment of TB in countries;
• To assist and facilitate the implementation and evaluation of activities listed in the strategic plan
Established April 2012; 12 members + 2 observers
Task Force for new TB drug policy development
• Introduction of new anti-TB drugs in practice is a multistage process; • Development of appropriate combination(s) of drugs needs efficient
coordination and sharing of data between key partners;• Introduction of new TB drugs should be adaptable to countries settings
according to country's own health infrastructure and preparedness;• Need for rapid approval of new TB drugs by regulatory authorities in
high-TB burden countries so as to favor due access;• Equitable access to new drugs to all patients in needs worldwide is
essential and should be linked with measures to prevent misuse of the drugs;
• WHO has a key role to play for the development of policy recommendations for rational introduction and use of new drugs/regimens in programmatic settings, ensuring proper, equitable and cost-effective access to treatment.
The Strategy Plan - Principles
I. Determination of the type of evidence and data that would be required by WHO to recommend the use of new drug(s)/ regimen(s) for the treatment of DS and/or MDR-TB
• Review of current drug/regimen development landscape• Review of requirements for licensure by stringent regulatory
authorities• Determination of data according to indications (DS or DR-TB)
and populations (children, PLHIV)• Priority categories (fundamental -> nice to have)
The Strategy Plan – Contents (1)
II. Production of information notes:
• aimed at facilitating the production of policy recommendations for the treatment of TB (all forms), according to progress made in the development of new drugs/combinations of drugs
• Information notes:– to countries – to drug/regimen developers – to regulators – on compassionate use
The Strategy Plan – Contents (2)
III. Development of a "Policy Development Framework” for the introduction of new TB drugs/regimens in countries.
• Describes the process for development of policies for treatment of TB including the new drugs/regimens.
• Will be used to guide development of policy recommendations for specific drugs/regimens as data become available– based on progress of new drugs/drug combinations along clinical
development pathway (e.g. PK and drug-drug interaction studies, Phase II trials, Phase III pivotal trials),
– approval by stringent regulatory authorities (FDA, EMA, …).
• Will be used by the expert committees that will be convened by WHO to update/revise policy recommendations as needed.
The Strategy Plan – Contents (3)
IV. Plan for expert consultations on revision of treatment guidelines (depending upon drug pipeline development)
• Timing of meetings (through 2012-2014)• Drugs/regimens to be assessed• Preparation of key data• Experts selection & planning• Discuss with GRC - Rapid advice approach ?• Include time for STAG submission/endorsement and finalization of
policies
The Strategy Plan – Contents (4)
V. Market introduction
• map-out the detailed expertise needed (drug market introduction, pricing, funding, public vs. private issues) and identify appropriate stakeholders (incl. GF; UNITAID; GDF; CHAI, etc)
• Evaluate market shortcomings and commodity access issues
• Identify potential obstacles related to introduction and work with stakeholders (countries, drug developers, economists, market specialists, NGOs, donors…) to optimize market introduction.
The Strategy Plan – Contents (5)
VI. Introduction in countries• Country preparedness
– Background epidemiological data ("know your epidemics")– Health infrastructure– NTP structure
• Country support to enable access to new drugs – Strengthened capacity for diagnosis, drug resistance surveillance,
pharmacovigilance– Standardized definitions of outcomes (harmonize data collection after drug
introduction)– Drug supply and management– Discuss check/control mechanisms (accreditation)– Develop "Demonstration sites" for initial deployment of new drugs with
harmonised methods and surveillance
The Strategy Plan – Contents (6)
Overview of the presentation
• Background – Global TB burden
• Challenges in introducing new TB drugs/regimens
• Developing Guidance to countries
• A pluri-partners model
• Ensure equitable access to new drugs to all patients in needs worldwide and avoid acquisition of new resistances
• Identify suitable drug combination(s) for treatment of DS and DRTB early
• Need to work on country preparedness and clarify conditions for controlled/accredited access to new drugs
• Encourage collaboration between drug developers, regulators, and programme managers
• Find the suitable balance for easy access to new therapies and guarantee patients protection with use of drugs that remain efficient and safe worldwide
Key messages
• Dialogue needed with drug/regimen developers, sponsors, regulators, National TB Programme Managers.
• Information Notes:– Drafts circulated to partners/stakeholders for comments
and feed-back to ensure buy-in – To be finalised and disseminated in Oct-Dec 2012
• Meetings with stakeholders:– Task Force– Satellite meeting at International Conference of Drug
Regulatory Authorities (ICDRA), Tallinn (22 Oct 2012)– Meeting at International Conference on Lung Health,
Kuala Lumpur (Nov 2012)
A pluri-partners model
• As unique forum grouping representatives from key drug development initiatives, CPTR has a critical role to play in the dialogue with key stakeholders.
• Contribute/promote interactions – e.g. through
- Global Regulatory Pathway Working Group
- Working Group on Access and Appropriate Use
• Contribute to works of the Task Force for New Drug Policy Development – technical resource
• Later stages ?
A role for CPTR
• Task Force members
• WHO staff, particularly Samvel Azatyan, Dennis Falzon, Christopher Fitzpatrick, Malgosia Grzemska, Ernesto Jaramillo, Shanthi Pal, Andrea Pantoja, Charles Penn, Lembit Rägo, Mario Raviglione, Diana Weil & Karin Weyer
• BMGF; USAID; DfID
Acknowledgements