Developing New Drugs to Control TB William Wells, Ph.D. Director, Market Access Global Alliance for TB Drug Development (TB Alliance) Journalist to Journalist.

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