1. Chair, DR-TB STAT Task Force
Rollout of Novel Drugs and Regimens for DR-TB: Implications for Scale-Up
Jennifer Furin, MD., PhD
Chair, DR-TB STAT Task Force
Harvard Medical School, Department of Global Health and Social Medicine

2. Objectives
Describe novel therapeutics in TB and their advantages over current SOC
Discuss progress of introduction in comparison with goals, including challenges to scale-up
Review promising novel therapeutic strategies and timelines for launch
Discuss goals for success in including how STBP can assist with reaching these goals

3. Novel Therapeutic Strategies: Exciting Times for DR-TB!
Bedaquiline
Delamanid
Shortened Regimen
PA-824
Carbapenems
Dose optimization of linezolid
Advantages: improved outcomes, toxicity management, shorter overall regimens

4. DR-TB STAT
Formed in April, 2015 in response to the “Call to Action” to accelerate access to new drugs for MDR-TB
Officially adopted as a GDI task force in July 2015
Multiagency participation
Activities include monitoring and support for new drug introduction
Budgets 50K in 2015, 55K in 2016
Most work donated or done pro bono

5. Bedaquiline Progress 5234 as of September 1, 2016
60% in South Africa, 20% Russia
4663 orders from GDF
As of May 1, 2016, BDQ has been registered in 12 countries including Armenia, the European Union, India, Macau, Peru, Philippines, Russia, South Africa, South Korea, Taiwan, Turkmenistan, the United States, Uzbekistan. Dossiers have been submitted to an addition 17 countries
Dossiers have been submitted in Azerbaijan, Bangladesh, Belarus, China, Colombia, Hong Kong, Indonesia, Kazakhstan, Mexico, Moldova, New Zealand, Tanzania, Thailand, Uganda, Viet Nam. Of note, a dossier submitted in Kyrgyzstan was rejected on the basis that there was no phase III data. Additionally a joint application has been submitted for the following countries via a WHO pilot project for collaborative registration: Burundi, Cameroon, Ethiopia, Ghana, Kenya, Nigeria, Tanzania

6. Bedaquiline Map

7. Delamanid 363, all in MSF or PIH sites 1018 orders from GDF
DLM has been registered in Japan, South Korea, Hong Kong, and the European Union and is not registered in any high-burden countries.
Dossiers have been submitted for registration in the Philippines, Indonesia, Turkey and Vietnam.

8. Delamanid Map

9. Global Progress: BDQ and DLM

10. BDQ and DLM versus Minimum Estimated Goal

11. Access Gap Patients in desperate need
Companies see no market (i.e. “cannot even give drug away”)
Revealed multiple opportunities to contribute to MDR-TB treatment scale-up overall

12. Three types of countries
“Go” countries
“Slow” countries
“No” countries

14. Challenges to Successful Intro
Lack of urgency
Process for updating recommendations and guidelines—delayed BDQ updates, peds guidance, 2016 update without mention of new drugs
Genuine confusion over the WHO recommendations
“Exceptionalization” of new drugs, focus on protecting drug
GLCs: actively block and stop treatment with new drugs, not aware of emerging data
Persisting perceptions that these drugs are dangerous of difficult to use
Persisting concerns about active PV
TA but is it the right kind?
Affordable price necessary but not sufficient
Courtesy of Tara Loyd

15. Shortened MDR-TB Regimens
Recommended by the WHO in May, 2016 for specific group of patients (but no mention of complementary use of new drugs)
Based on observational cohort data from a number of Francophone African countries, Bangladesh, but all used slightly different regimens in populations with limited exposure to SLDs, low rates of SLD resistance
STREAM trial results due in late 2017

16. Implementation Plans
Pilot programs started or being planned in multiple countries
Scale-up occurring in most sites where the observational cohorts occurred
Logisitical challenges around access to SLDST, management of patients while awaiting SLDST, what to do in settings with high rates of PZA/EMB/Ethio resistance
High rates of AEs still seen (41% hearing loss)
Substitution of other drugs in regimen (i.e. BDQ)

17. Future Possibilities Phase III delamanid trial, Q4 2017/ Q1 2018
endTB trial: October 2016-results 2021
PRACTECAL: Q results 2021
Next: enrolling-results 2020
A5343: enrolling—results 2019
A5356: planned
NiX: enrolling—results 2018
MDR-END: Q4 2016—results 2020
STAND: clinical hold
Delamanid safety and PK in children (almost complete)
Bedaquiline saefty and PK in children (just started)
Prevention trials: V-QUIN, CHAMP, PHOENiX

18. Novel Formulations Pediatric TB: 150,000 courses already ordered
SLDs: very little interest in newly development formulations
PedDRTB dosing system
Gel formulations in early development
Often more expensive
Reveals major gaps in diagnosis and treatment of DR-TB in children -

19. Need to Address Barriers to Rollout Now
Or it will be 2030 before these interventions are in place!
Improved monitoring and support around novel interventions
Streamlined process for updating WHO recommendations
Service-based model of TA
Inclusion of implementation experts

20. Specific Requests to STBP
For DR-TB STAT, earlier release of adequate funding
Civil society pressure/demand generation
Human rights framework on access to benefits of science
Utilization of expert networks (STAT, Sentinel)
“TB REACH”-like process for scaling up novel interventions

21. Thank you! jenniferfurin@gmail.com