Access to TB Drugs and Diagnostics Gregg Gonsalves Open Society Foundations Division of the Epidemiology of Microbial Diseases, Yale School of Public Health Department of Global Health and Social Medicine, Harvard Medical School

The global TB situation Estimated number of cases, 2010 Estimated number of deaths, 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 ( ) * 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 population TB Incidence Rates 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 % 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-TB Available 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, 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 All rights reserved

Proportion of MDR among previously treated TB cases Latest available data, 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 All rights reserved

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

Treatment Evolution for “Drug Sensitive” TB st regimen: Streptomycin PAS Isoniazid (H) 1963 Rifampin (R) discovered 1974 BMRC Trials add R & Z Pyrazinamide (Z) discovered – but liver toxicity Rx lasts from months Standard Regimen by 1960s based on 1952 drugs 1970 BMRC 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 Strepto- mycin 1 st 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). 11

MDR-TB Drug Prices

► Significant improvements in therapy are needed for all patient populations Patient Population Current Therapy Unmet Needs Drug-Susceptible TB 4 drugs; ≥6 month therapyShorter, simpler therapy Drug-Resistant M(X)DR-TB Few drugs (including injectables); ≥18 months therapy; toxicities Totally oral, shorter, more efficacious, safer and lower cost therapy TB/HIV Co-Infection Drug-drug interactions with HIV medications Ability to co-administer TB regimens with ARVs Latent TB Infection 6-9 months of treatmentShorter, safer therapy Children 4 drugs; ≥6 month therapy Shorter, 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

Distance from Patients Intermediate level Lab Reference level New SS+ case definition 2-specimen approaches POC test (detection) Peripheral level Abbreviations DST: Drug susceptibility test NAAT: Nucleic acid amplification test LTBI: Latent TB infection POC: Point of care MODS: Microscopic observation drug-susceptibility NRA: Nitrate reductase assay CRI: Colorimetric redox indicator assay LED: Light-emitting diode LPA: 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 after 5 years Predictive LTBI Xpert MTB/RIF Rapid colorimetric DST Manual NAAT 1 st generation Manual NAAT 2 nd 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!