Developing New Drugs to Control TB William Wells, Ph.D. Director, Market Access Global Alliance for...
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Transcript of Developing New Drugs to Control TB William Wells, Ph.D. Director, Market Access Global Alliance for...
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
The need for new TB drugs
• The need to ensure adherence can put a huge burden on patients
• Shorter therapies equals > adherence, > cure, < burden on patients, and < emergence of drug resistance
Current TB Therapy and Unmet Needs
Drug-sensitive TB4 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 Infection9 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
TB Alliance
• Founded in 2000
• Not-for-profit Product Development Partnership (PDP) headquartered in New York, with offices in Brussels and Pretoria
• Entrepreneurial, virtual drug development approach
• Largest portfolio of TB drug candidates in history
TB Alliance
PHARMABIOTECH
ACADEMIA INSTITUTES
GOVERNMENTS
FOUNDATIONS
Operating Model
In-licensing and independent development
PA-824 (Chiron/Novartis)
Collaborative R&D with affordability commitment
Moxifloxacin (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:
Why are PDPs needed?
There is a “market failure” for diseases found solely or predominantly in 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)
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 per year estimated to be needed to reach Global Plan to Stop TB targets
TB R&D funding by sector, 2008
TB Alliance VisionFDCs
2 – 4 months
6 – 30 months
10 days
Success will require novel multi-drug
combinations
Global Clinical Portfolio - New TB Drugs in Registration Programs
Bayer, TB AllianceBayer, TB Alliance
Oflotub, TDROflotub, TDR
Tibotec, TB AllianceTibotec, TB Alliance
OtsukaOtsuka
TB AllianceTB Alliance
SequellaSequella
LupinLupin
PfizerPfizer
Phase IPhase I
Phase IIPhase II
Phase IIIPhase III
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 endemic markets.
Formulate strategy, but work through partners and existing structures. 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.
Demand Forecast(Moxi Demand Forecast)Demand Forecast(Moxi Demand Forecast)
Define issues for users(Value Proposition Study)
Define issues for users(Value Proposition Study)
Understand the regimenchange process(Country Introduction Study)
Understand the regimenchange process(Country Introduction Study)
Support local decision-making (cost-benefit)
Support local decision-making (cost-benefit)
Devise local launch strategy• Stakeholder and partner mapping and engagement• Document resources for operational research, financing, TA, retraining
Devise local launch strategy• Stakeholder and partner mapping and engagement• Document resources for operational research, financing, TA, retraining
Engage funding and procurement agencies
Engage funding and procurement agencies
MarketAccessStrategy
MarketAccessStrategy
Regulatory StrategyRegulatory Strategy
ManufacturingStrategyManufacturingStrategy
UnderstandExisting Market(Market Study)
UnderstandExisting Market(Market Study)
IP agreementsIP agreements
Engage guideline-setting agencies (WHO and others)
Engage guideline-setting agencies (WHO and others)
Pricing StrategyPricing StrategyConsumer marketingConsumer marketing
Market Study Conducted with IMS HealthPublished May 2007
Map TB drug market in 6 key high burden & 4 high income countries
Understand flow of drugs to prepare for launch
Fragmented, local markets
Size the existing global TB drug market
Estimate to inform TB Alliance deals and strategy
Global market of ~US$315m including all four first-line drugs
What Countries Want Value Proposition StudyPublished August 2009
Most stakeholders would welcome treatment shortening as the primary goal. Unacceptable trade-offs in all countries:
• Decreased efficacy
• Additional safety concerns or side effects requiring monitoring or expensive adjuvant therapies
• Significant drug interactions with other commonly-used drugs (including ARVs)
Unacceptable trade-offs in some countries:
• Treatment frequency significantly different from current TB program (e.g., India)
• Unavailability in fixed-dose combination (FDC)
Summary
Great need for new drugs to address the challenges 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 a stronger global TB drug pipeline and fulfill our vision
Thank You
REMoxTB Trial Design
1 2 3 4 5 6
Treatment Duration (months)
HRHRZE800 participants
Standard regimen
ContinuationIntensive
Placebos
HRZM HRM
Placebos
800 participants
Moxifloxacin for
Ethambutol
MRZE MR
Placebos
800 participants
Moxifloxacin for
Isoniazid
All pts followed for 12 months post-treatment end
Randomized, double-blind; non-inferiority