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Developing New Drugs
to Control TB
William Wells, Ph.D.
Director, Market Access
Global Alliance for TB Drug Development (TB Alliance)
Journalist to Journalist Project, IUATLD Meeting
Cancun, Mexico, December 4, 2009
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The need for new TB drugs
The need to ensure adherence can put a huge burden onpatients
Shorter therapies equals > adherence, > cure, < burdenon patients, and < emergence of drug resistance
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Current TB Therapy and Unmet Needs
Drug-sensitive TB
4 Drugs, 6 months
M(X)DR-TB
Few drugs (including injectables);
18 months; severe side effects
TB/HIV co-infection
Drug-drug interactions with ARVs(antiretroviral agents i.e.,HIV/AIDS drugs)
Latent TB Infection
9 months of isoniazid
Shorter therapy
More effective, safer drugs;
shorter, simpler therapy
Co-administration with ARVs
Shorter therapy
Unmet NeedsCurrent Therapy
No new drugs for TB in 40 years; no market incentive
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TB Alliance
Founded in 2000
Not-for-profit ProductDevelopment Partnership(PDP) headquartered in New
York, with offices in Brusselsand Pretoria
Entrepreneurial, virtual drugdevelopment approach
Largest portfolio of TB drug
candidates in history
TB
Alliance
PHARMABIOTECH
ACADEMIA INSTITUTES
GOVERNMENTS
FOUNDATIONS
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Operating Model
In-licensing and independent development
PA-824 (Chiron/Novartis)
Collaborative R&D with affordability commitmentMoxifloxacin (Bayer); GSK mini portfolio (GSK); TB drug portfolio (Novartis);TMC-207 (J&J)
Contracted R&D with IP rights
Quinolone (KRICT); Nitroimidazole (ACSRC); Riminophenazine (IMM);Phenotypic screening (UIC); Energy metabolism (UPenn); Protease (IDRI);Tryptanthrine (KRICT); RNAP (Rutgers); LeuRS (Anacor); Menaquinone (CSU);Topo I (NYMC); Natural products (IMCAS)
A flexible, virtual R&D approach:
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Why are PDPs needed?
There is a market failure for diseases found solely or predominantlyin low income countries
Private sector: Cannot justify such large expenditure when the returns are so low Prior to the PDPs, most products that were useful only in low income countries
were discovered by accident (e.g., veterinary product) or for military or tourists
Academic researchers: Publicly funded
Have the interest in pursuing neglected diseases But do not have the means to do so (large chemical libraries, screening facilities,
networks of trials sites and the staff to run them)
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Private investment is not enough to support TB R&D
Funding for all TB R&D (basic, drugs, diagnostics, vaccines,operational) is US$510m per year, compared to the US$2 billion peryear estimated to be needed to reach Global Plan to Stop TB targets
TB R&D funding bysector, 2008
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TB Alliance Vision
2 4 months
6 30 months
10 days
Success will requirenovel multi-drug
combinations
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Global Clinical Portfolio - New TB
Drugs in Registration Programs
Bayer, TB Alliance
Oflotub, TDR
Tibotec, TB Alliance
Otsuka
TB Alliance
Sequella
Lupin
Pfizer
Phase I Phase II Phase III
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TB Alliance Market Access
Focused on the AAA strategy: Available (supply chain, forecasting, registration, distribution strategy);
Affordable (pricing strategy, donor policies);
Adopted (issues and evidence for key decision makers).
Ensure that products are suited for, and wanted by, those in endemicmarkets.
Formulate strategy, but work through partners and existingstructures. Need to understand the process so we can facilitate coordination.
WHO recommendation is essential.
Existing Ministry of Health and NGO programs will deliver the drugs.
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Demand Forecast(Moxi Demand Forecast)
Define issuesfor users(Value Proposition Study)
Understand the regimenchange process
(Country Introduction Study)
Support localdecision-making(cost-benefit)
Devise local launchstrategy Stakeholder and partnermapping and engagement
Document resourcesfor operational research,financing, TA, retraining
Engage fundingand procurementagencies
Market
AccessStrategy
Regulatory Strategy
ManufacturingStrategy
UnderstandExisting Market(Market Study)
IP agreements
Engage guideline-setting agencies(WHO and others)
Pricing StrategyConsumer marketing
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Market StudyConducted with IMS HealthPublished May 2007
Map TB drug market in 6 key highburden & 4 high income countries
Understand flow of drugs toprepare for launch
Fragmented, local markets
Size the existing global TB drug market
Estimate to inform TB Alliance dealsand strategy
Global market of ~US$315m includingall four first-line drugs
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What Countries WantValue Proposition Study
Published August 2009
Most stakeholders would welcome treatment
shortening as the primary goal.
U
nacceptable trade-offs in all countries: Decreased efficacy
Additional safety concerns or side effects requiringmonitoring or expensive adjuvant therapies
Significant drug interactions with other commonly-used drugs (including ARVs)
Unacceptable trade-offs in some countries: Treatment frequency significantly different fromcurrent TB program (e.g., India)
Unavailability in fixed-dose combination (FDC)
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Summary
Great need for new drugs to address thechallenges and unmet needs in TB therapy
Resurgence in TB drug R&D; up to 2-3 new
drugs could reach registration by 2015
Increased funding is needed to support astronger global TB drug pipeline and fulfill our
vision
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Thank You
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REMoxTB Trial Design
1 2 3 4 5 6
Treatment Duration (months)
HRHRZE800 participants
Standard regimen
ContinuationIntensive
Placebos
HRZM HRM
Placebos
800 participants
Moxifloxacinfor
Ethambutol
MRZE MR
Placebos
800 participants
Moxifloxacinfor
Isoniazid
All pts followed for 12 months post-treatment end
Randomized, double-blind; non-inferiority