Access to TB Drugs and Diagnostics

Gregg GonsalvesOpen Society Foundations

Division of the Epidemiology of Microbial Diseases, Yale School of Public HealthDepartment of Global Health and Social Medicine, Harvard Medical School

The global TB situationThe global TB situation

Estimated number of cases, 2010

Estimated number of deaths, 2010

1.1 million*(0.9–1.2 million)

8.8 million(8.5–9.2 million)

~ 650,000 out of 12 million (11-14 million)

prevalent TB cases

All forms of TB

Multidrug-resistant TB

HIV-associated TB 1.1 million (1.0–1.2 million)

350,000(320,000–390,000)

Source: WHO Global Tuberculosis Control Report 2011 (www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf)* Excluding deaths attributed to HIV/TB

0–24

25–49

50–99

100–299

>300

No estimate

•Highest burden in Asia (55% of 9.4 million cases)

•Highest rates in Africa, due to high HIV infection rate~80% of HIV+ TB cases in Africa

Per 100 000 population

TB Incidence Rates - 2009

Africa 30%

West Pacific 20%

SE Asia 35%

Europe 4%

East Mediterranean 7%

Americas 3%

Impact of HIV on TB in Africa

Notified cases per 100,000 pop. 1980-2008

•79% of all TB/HIV cases world-wide are in Africa•50% of all TB/HIV cases world-wide in 9 African countries•23% of the estimated 2 million HIV deaths due to TB

Time trends in MDR-TBTime trends in MDR-TBAvailable data from 74 countries and territories with measurements for at least two years could not answer the question of whether the proportion of previously untreated TB cases with MDR was increasing, decreasing or stable over time at a global or regional level.

Proportion of MDR among new TB cases Latest available data, 1994-2010

0-<3

3-<6

6-<12

12-<18

>18

No data available

Subnational data only

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines

for which there may not yet be full agreement. WHO 2011. All rights reserved

0-<6

6-<12

12-<30

30-<50

>50

No data available

Subnational data only

Proportion of MDR among previously treated TB cases Latest available data, 1994-2010

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines

for which there may not yet be full agreement. WHO 2011. All rights reserved

Countries that had reported at least oneXDR-TB case by Oct 2011

Argentina Burkina Faso Estonia Japan Namibia Republic of Korea The Former Yugoslav Republic of MacedoniaArmenia Bhutan France Kazakhstan Nepal Republic of Moldova TogoAustralia Cambodia Georgia Kenya Netherlands Romania TunisiaAustria Canada Germany Kyrgyzstan Niger Russian Federation TurkeyAzerbaijan Chile Greece Latvia Norway Slovenia UkraineBangladesh China India Lesotho Pakistan South Africa United Arab EmiratesBelarus Colombia Indonesia Lithuania Peru Spain United KingdomBelgium Czech Republic Iran (Islamic Rep. of) Mexico Philippines Swaziland United Republic of TanzaniaBenin Dominican Republic Ireland Mongolia Poland Sweden United States of AmericaBotswana Ecuador Israel Mozambique Portugal Tajikistan UzbekistanBrazil Egypt Italy Myanmar Qatar Thailand Viet Nam

Treatment Evolution for“Drug Sensitive” TB

1950 2005

1952 1st regimen:

• Streptomycin• PAS• Isoniazid (H)

1963 Rifampin (R) discovered

1974 BMRC Trials add R & Z

1970

1954Pyrazinamide (Z)

discovered – but liver toxicity

Rx lasts from 12-24 months

Standard Regimen by 1960s based on 1952 drugs

1970BMRC Trials add R

Rx shortened to 9 months

Standard Therapy 2 months: R, H, Z, E

+4 months: R, H

Rx shortened to 6 months

19801960

1946Strepto-mycin 1st

used for TB

1998 Rifapentine approved

1961 Ethambutol (E)

discovered

9

The Burden of Therapy for Multi-drug Resistant TB

Example of a typical regimen for MDR-TB•Intensive phase of 6-9 months – aim to directly observe 6 days/week:

– Six drug combination, one given by injection•Continuation phase of 18 months:

– Four drugs•A patient may need longer therapy if sputum is not clear of TB at month 4

Note: If the patient has HIV, he/she may need to take 3 additional anti-retroviral drugs

10

The Burden of Therapy for Multi-drug Resistant TB

• The price of four medicines in particular weigh heavily in the overall cost of a DR-TB regimen. Overall costs of the DR-TB regimen are particularly driven by capreomycin, moxifloxacin, PAS, and cycloserine.

• For most DR-TB drugs, patents are not typically a factor in causing high prices, because the medicines were developed so long ago that patents on most have long run out. However, moxifloxacin is a notable exception—until now, Bayer’s monopoly has kept prices high.

• Some DR-TB drug prices have increased considerably between 2001 and 2011, including for the medicines procured through the GDF for GLC-approved treatment programs. This is true of the prices of amikacin (the most affordable source in 2011 costs eight times more the most affordable source in 2001), kanamycin (six times more), cycloserine, and capreomycin (both three times more). 1

1

MDR-TB Drug Prices

► Significant improvements in therapy are needed for all patient populations

Patient Population

CurrentTherapy

UnmetNeeds

Drug-Susceptible TB 4 drugs; ≥6 month therapy Shorter, simpler therapy

Drug-ResistantM(X)DR-TB

Few drugs (including injectables); ≥18 months therapy; toxicities

Totally oral, shorter, more efficacious, safer and lower cost therapy

TB/HIVCo-Infection

Drug-drug interactions with HIV medications

Ability to co-administer TB regimens with ARVs

Latent TBInfection 6-9 months of treatment Shorter, safer therapy

Children 4 drugs; ≥6 month therapyShorter, simpler therapy with pediatric-friendly dosing

Current TB Therapy and Unmet Needs

13

The Global TB Development Pipeline

From the Stop TB Partnership Working Group on New Drugs

14

Tuberculosis Diagnosis: Then and Now

The Future of TB Diagnostics

– Xpert MTB/RIF :• Level of the Health system: Peripheral laboratory,

at district and sub-district level (intended for use in secure facilities with a reliable source of electricity)

• For LICs and MICs FIND negotiated a 75% reduction relative to the market price:

• $16.86 per cartridge• $17,000 - $17,500 per Instrument• But• Not the POC diagnostic that is needed.

Xpert MTP/RIF

• Point-of-care: easy to perform in peripheral health centres

• Detect active TB in adults regardless of HIV status• Improved diagnosis of TB in children• Result that allow decision on treatment initiation • Patient can receive result on the same day

The TB Test We Need

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Dis

tanc

e fr

om P

atien

ts

Intermediate level Lab

Reference level

New SS+ case definition

2-specimen approaches

POC test (detection)

Peripheral level

AbbreviationsDST: Drug susceptibility testNAAT: Nucleic acid amplification testLTBI: Latent TB infectionPOC: Point of careMODS: Microscopic observation drug-susceptibilityNRA: Nitrate reductase assayCRI: Colorimetric redox indicator assayLED: Light-emitting diodeLPA: Line probe assay

Technologies or methods endorsed by WHO

Rapid speciation

Liquid culture & DST

LPA for MDR-TB

Non-commercial culture & DST (MODS, NRA,CRI)

LPA for XDR-TB

10-40%

70%

95%

% Access aft

er 5 years

Predictive LTBI

Xpert MTB/RIF

Rapid colorimetric

DST

Manual NAAT 1st generation

Manual NAAT 2nd generation

Technologies at late stages of development

Technologies at early stages of development

LED microscopy

Same-day diagnosis

Tonight! From 7-8PM

Meet in Hotel Lobby(with guest Salmaan Keshavjee, Harvard Medical

School/Partners in Health)

Let’s Start a Campaign to Drop the Price of MDR-TB Drugs!