TB Pharmaceuticals (William Wells, M.I.A., Ph.D.)

8/7/2019 TB Pharmaceuticals (William Wells, M.I.A., Ph.D.)

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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

TB Pharmaceuticals (William Wells, M.I.A., Ph.D.)

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