2. Global programmatic use of bedaquiline and delamanid for drug-resistant TB treatment: progress, challenges, and possible solutions
Dr. Vivian Cox
Chair, DR-TB Scale-Up Treatment Action Team (DR-TB STAT) Task Force
USAID/STBP MDR-TB Clinical Consultant

3. Conflict of interest disclosure
This event is accredited for CME credits by EBAP and speakers are required to disclose their potential conflict of interest going back 3 years prior to this presentation. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgment. It remains for audience members to determine whether the speaker’s interests or relationships may influence the presentation. Drug or device advertisement is strictly forbidden.
Conflict of interest disclosure
X I have no, real or perceived, direct or indirect conflicts of interest that relate to this
presentation.
I have the following, real or perceived direct or indirect conflicts of interest that relate to this presentation:
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4. Outline Global progress on introduction of newer drugs
Uptake of BDQ and DLM in the PAHO region
Barriers to newer drug access
Potential solutions

5. Timeline: introduction of bedaquiline and delamanid
December 2012
FDA grants accelerated approval for bedaquiline
June 2013
WHO releases interim guidelines for use of bedaquiline to treat DR-TB
March 2014
EMA conditionally approves bedaquiline
April 2014
EMA conditionally approves delamanid
October 2014
WHO releases interim guidelines for use of delamanid to treat DR-TB
May 2015
WHO adds bedaquiline and delamanid to Essential Medicines List
April 2015
Janssen/USAID launch bedaquiline donation program
Otsuka announces FighTBack Initiative delamanid donation program
October 2015
Georgia becomes first country to receive donated bedaquiline
October 2016
WHO guideline update on the use of shorter MDR-TB regimen
WHO releases guidance on delamanid use for DR-TB in children
March 2017
WHO releases GDG meeting report on the use of bedaquiline for DR-TB
September 2017
WHO releases statement on off-label use of bedaquiline and delamanid
December 2017
Five years after bedaquiline approval

6. Progress of global BDQ introduction
10,164 patients have received BDQ as of 1 July 2017
13,825 orders from the Global Drug Facility
Registered in 18 countries; under assessment in 16 (11/30 high DR-TB burden countries without submission)
80% of BDQ access in South Africa and Russia
3,441

7. Global BDQ implementation
*As of 1 July 2017

8. Progress of global DLM introduction
688 patients have received DLM as of 1 July 2017
3,238 orders from the Global Drug Facility
Registered in 6 countries; under assessment in 4 (25/30 high DR-TB burden countries without submission)
79% of DLM access through Unitaid endTB project
*adjusted to exclude compassionate use of DLM in November 2016

9. Global DLM implementation
*As of 1 July 2017

10. Global Progress: BDQ and DLM
*adjusted to exclude compassionate use of DLM in November 2016

11. Global progress: BDQ and DLM versus minimum estimated global need
*calculation of global estimated need for newer drugs adjusted to reflect cumulative number of
patients started on treatment for RR-TB in 2015 and 2016

12. 14% (OOS 5%)

13. Uptake of BDQ and DLM: PAHO region
Brazil is a high-burden TB country and Peru is a high-burden MDR-TB country
Overall it is estimated that there are more than 7,000 persons in the PAHO region who needed newer drugs over the two year period between 2015 and 2017
Fewer than 150 people in the PAHO region have received newer drugs under program conditions, just over 2% of those who needed them
PAHO countries that have introduced newer drugs under program conditions: Peru, Haiti and the Dominican Republic
Brazil: compassionate use access for newer drugs
Delamanid orders via GDF only for Dominican Republic (4 treatments)
Bedaquiline orders via GDF for Dominican Republic (34 treatments), Peru (211 treatments), Haiti (20 treatments), Bolivia (3 treatments)

14. Reported barriers to newer drug introduction (1)
Guidelines
Interpretation of WHO guidelines in country context
Guideline revision process, including training
Concerns about off label use and use in special populations, especially with donation program drugs
Establishing PV / aDSM
Wanting to collect own efficacy data
Adding newer drugs to a long, toxic regimen
Cost, registration, importation
Health system strengthening

15. Reported barriers to newer drug introduction (2)
Guidelines
Cost, registration, importation
BDQ: donation program or tiered pricing; DLM: GDF pricing
Registration (BDQ: 18 countries; DLM: 6 countries)
Health system strengthening
Weaknesses in current DR-TB programme
Restriction of newer drug use to few centralized facilities
Requirement to hospitalize cases to initiate newer drugs
Lack of monitoring equipment
Lack of SL LPA and/or phenotypic DST
Weak community support systems for DR-TB patients
Poor support from Ministry of Health

16. Contrast in access to BDQ and DLM
Timeline of WHO recommendations doesn’t fully explain differential use
Potential reasons for gap in access:
Cost – purchase from GDF started in Feb 2016, only if GF-eligible
Registration – proactivity of Janssen (e.g. CRP)
Early access programmes – built clinical experience in country
Country level decisions – sequential systems for BDQ then DLM
BD dosing – impact on DOTS programmes and resources

17. Global access to newer drugs: potential solutions
WHO guideline recommendations update
Expand/re-organize technical assistance to countries to absorb current and future innovations
Streamline pre-qualification and registration processes for new drugs
Engage and educate communities on newer drugs
Set targets
Country targets
Regional targets
Access, registration, time to patient targets
Set targets before access is needed
Engage with civil society to create accountability

18. Acknowledgements