Progress in

Global TB
Drug
Development
Cherise P. Scott, Ph.D., MPH
Director, Pediatric Programs
National Press Foundation
December 2, 2015
Cape Town, South Africa

Childhood TB: Hiding in the shadows

Children with TB are the neglected of the neglected
TB is a significant cause of death
among children; children are
susceptible to the most severe and
fatal forms of TB
In 2014, an estimated 1 million
children became ill with TB and 140
000 children died of TB
Children with TB have been
historically neglected many go
undiagnosed and untreated
Child health and survival is
improving, with fewer deaths from
diseases such as HIV and
pneumonia. But TB lingers, and lacks
attention and resources dedicated to
the problem

Introduction of Child-

New guidelines, old drugs

Market unresponsive to call for new treatments
In 2010, WHO revised dosing guidelines for TB drugs for children
based on evidence that children were not receiving enough TB
medicine
Drug

Previous WHO
Guidance

Current WHO
Guidance

Dose and range

(mg/kg body weight)

Dose and range (mg/kg

body weight)

Isoniazid

5 (4-6)

10 (7-15)

Rifampicin

10 (8-12)

15 (10-20)

Pyrazinamid
e

25 (20-30)

35 (30-40)

Ethambutol*

20 (15-25)

20 (15-25)

*depending on setting and type of disease

The guidance and policy changed, but the products available for
treatment of children did not change
Many providers must crush or chop available tablets to achieve 3

Challenges of administering treatment

Delivering current treatment is complex and
burdensome

Dosing chart for pediatric

TB therapy in the
Philippines. Treatment
administered via syrups.

Dosing chart for pediatric TB

therapy in South Africa.
Treatment administered via
pills.

Introduction of Child-

Pharmacist preparing syrups of

Rifampicin for pediatric TB
treatment in Thailand.

Value of improved, child-friendly FDCs

Advocate for Access!

Child-friendly TB medicines in the correct

doses are now available and can improve
adherence and child survival from TB

Countries must register and adopt these

products immediately
6

Call to Action
Please sign the Call to Action and show your support for
a TB-free Future by visiting tballiance.org/signthecall
COMMUNITY / CARE GIVERS
- Ask about availability of new
products
- Learn about TB and its
symptoms in children

ADVOCATES
- Encourage your
country to register and
procure new products

GOVERNMENTS/HEALTH
PROGRAMS
- Quantify child TB in country
- Implement current guidelines
- Scale-up contact investigation
- Fast-track product registration
- Include Child TB in Budget and
Grants

EVERY
CHILD
HAS
ACCESS
TO THE
NEW
PRODUCT

DONORS
- Fund new products
- - Fund scale up of
effective interventions
for child TB

Our Vision: Better TB Medicines for

All
Dedicated to the discovery and
development of better, faster
and affordable TB drugs that are
available to all who need them
Achieving maximum impact will
require:
Short, simple regimen that is
affordable, available and
accessible
Universalregimen that is effective
in virtually all people with active
TB, erasing the distinctions of MDRTB or XDR-TB
All novel drugs, circumventing
challenges of resistance to some
antibiotics available today
TB Alliance Overview

Global TB Drug Pipeline

Accelerating Progress: From Drugs to Regimens

TB Alliance is searching for the best combinations of novel drugs
TB must be treated with multi-drug combinations to prevent the
development of resistance
Todays pipeline of TB drugs can be tested together, speeding
development of novel TB regimens and reducing R&D from
decades to years

TB Alliance Overview

10

TB Drug/Regimen Development
Discovery and Development Process
Discovery

Compound 1

Single Compound
Preclinical
Development
Phase I EBA

Compound 2

Regimen A

Compound 3
Compound 4
Compound 5

Phase II Phase III

Regimen B

Drug
Candida
te Pool

Regimen C

Regimen Identification
in Mice

Identification of New Drug

Candidates

Selection of Potential New

Regimens
11

Nix-TB Clinical Trial

XDR-TB could be a death
sentence. There are no effective
treatments. Salvage therapy can
last 2 years
Launched May 2015, Nix-TB is
the first clinical trial of an XDRTB regimen with minimal preexisting resistance
Tests a drug combination as a 69 month cure that is all pills, no
injections
First participant with XDR-TB
completed six-month study
treatment in November

A 2014 Lancet study found nearly

half of XDR-TB patients died within
a year of diagnosis.

Regimen could be first

universal treatment;TB
if safe
Alliance Overview

12

Nix-TB Clinical Trial

TB Alliance Overview

13

Global TB Drug Pipeline

14

Early-Stage Research: Filling the

Pipeline
TB Alliance is now a partner in the TB Drug Accelerator Project

Optimizing known
compound classes

Developing novel
classes based on
novel targets

TBA-354 Initiated single ascending dose

Phase 1 study. First new drug to enter the
clinic in six years
Oxazolidinone and Diarylquinoline
candidates to move into pre-clinical
development in 2016
DprE-1 inhibitor (AZ-7371) Novel
bactericidal compound with no pre-existing
resistance is approved to move into preclinical development
2 Lead Optimization and 2 Lead
Identification programs initiated

TB Alliance leverages industry and other partners to support the

continued growth of the global TB drug pipeline. MORE new
drugs are needed
TB Alliance Overview

15

Cost of Inaction
By 2030, a five-year delay in investment for new tools is estimated
to result in:

1) 8.4 MILLION
ADDITIONAL TB
CASES

2) 1.4 MILLION
ADDITIONAL TB
DEATHS

4) US$ 5.3
BILLION IN
ADDITIONAL
COSTS FOR TB
TREATMENTS
(US$ 7.5 billion
without discounting)

3) 39.8 MILLION
DALYS SUFFERED
(56.1 million without
discounting)

5) US$ 181
BILLION IN LOST
PRODUCTIVITY
(US$ 318 billion
without
discounting), valuing
each DALY at percapita GNI.

Source: Stop TB Partnerships Global Plan 2016-2020

Introduction of Child-

16

Learn more
Please attend: Improving Access to Appropriate
Childhood TB Medicines Luncheon Symposium,
December 3, 2015, 11:45-14:00, The Table Bay Hotel,
The Ballroom
Visit us at the TB Alliance booth
Come help us paint a mural for a TB Free Future.
Dedication on Friday at 12:15 pm. Location:
Conference center, IMBIZO Hall 4B
Visit us online at tballiance.org

Introduction of Child-

17

TB Alliance Supporters

Australian
Department of
Foreign Affairs and
Trade

Bill & Melinda

Gates
Foundation

European
Commission

Indonesia
Health
Fund

Global Health
Innovative Technology
Fund

UK aid

UNITAID

TB Alliance Overview

Irish Aid

United States
Food and Drug
Administration

US NIAID

United States Agency

for International
Development
18

Thank you!