Overview goes here
The WGND Annual Meeting serves as a neutral forum to bring together those working in development to get a full understanding of the progress, challenges, and critical issues in furthering TB drug development and achieving the objectives in the Stop TB Partnership's Global Plan.
- WGND UpdatesWelcomeMelvin SpigelmanStop TB Partnership, Global PlanCherise Scott
Overview of Global Plan to End TB 2016-2020 contributions, new drugs framework, total investment for new tools, and cost of inaction.
- The Global Plan to End TB 2016-2020 was created by a special committee, consultation with the community representatives, and online consultation with the broader community.
- Given the tremendous gains to be had by reaching the 90-(90)-90 targets by 2020, the Global Plan urges all countries to strive to implement the accelerated investment plan.
- By 2030, a five-year delay in investment for new tools is estimated to result in 8.4 million additional TB cases, 1.4 million additional TB deaths, USD 5.3 billion in additional costs for TB treatments, and USD 181 Billion in lost productivity.
https://www.newtbdrugs.org/sites/default/files/meetings/files/01_Cherise_Scott_STOP_TB_Partnership.pptxTB Drug Development Year-in-ReviewBarbara LaughonAn overview of 2015 milestones in TB drug research, updates to the pipeline, and the WGND webpage.
- Phase 1 trials of TBA-354 (TB Alliance) and Q203 imidazopyridine amide (Qurient) began in 2015.
- Novartis – Clofazimine Phase 2/3 trial planned to begin March 2016. OBR +\- clofazimine at 200 mg/day for 18 weeks then 100 mg/day.
- Several candidates in advanced preclinical development: TBI-166, CPZEN-45, SQ609, 1599, SEQ-9, PBTZ169, and BTZ043.
- More clinical candidates are needed to create a robust drug development pipeline and additional funding is urgently needed to advance promising early candidates into trials.
- Global Pipeline UpdateJanssen Pharmaceutical, Inc.Myriam Haxaire
Updates on bedaquiline development program including country usage maps, overview of Compassionate use/Expanded access, the Bedaquiline Donation Program in collaboration with USAID, information on the Global Drug Facility (see also: https://usaid.gov/what-we-do/global-health/tuberculosis/technical-areas/bedaquiline-donation-program), and implementation.
- Over 760 pre-XDR and XDR-TB patients have received bedaquiline in Compassionate use/Expanded Access Programs in 45 Countries (as of Sept 1, 2015).
- Countries participating in or under evaluation for MDR-TB multi-country registry include: South Africa, South Korea, China and India. Together with Russia, these countries represent ~60% of global estimated MDR-TB disease burden.
- The global supply of bedaquiline utilizes GDF in over 130 countries, the primary provider of quality assured second-line TB drugs worldwide.
Clinical Trials Unit, MRCAndrew NunnOverview of STREAM study design, results, status, and current partners for Stage 1 and design for Stage 2 and an overview of TRUNCATE regimen and strategy.
- STREAM is a randomized controlled trial of non-inferiority design comparing 9-month MDR-TB regimen with WHO recommended regimen; currently being conducted in Ethiopia, South Africa, Vietnam and Mongolia.
- Results from STREAM Stage 1 expected Q1/2 of 2018.
- STREAM Stage 2 assesses fully oral 9-month regimen and 6-month regimen, both containing bedaquiline.
- TRUNCATE is a strategy trial assessing long term outcomes of ultra-short course regimens; planning is underway.
TB AllianceChristo van NiekerkOverview and current status of STAND phase 3 trial and the role of PaMZ. Further updates on NC-005 trial, Nix-TB, and Dose-Ranging Linezolid Study.
- The STAND trial is the first phase 3 trial to test a regimen in patients with drug-sensitive and drug-resistant TB (must be sensitive to drugs in the regimen) and holds potential to transform treatment of both drug-sensitive and especially drug resistant TB.
- NC-005 tests regimens containing bedaquiline, PA-824, and pyrazinamide with the potential to even further shorten treatment for TB and MDR-TB, conducted at 10 sites in South Africa, Tanzania and Uganda, starting of October 2014.
- Nix-TB was launched May 2015. Nix is the first clinical trial for a novel XDR-TB regimen with minimal pre-existing resistance; all pills, no injections.
AIDS Clinical Trials Group (ACTG)Susan SwindellsOverview of the ACTG TB Transformative Science Group agenda, updates on TB portfolio studies and TB/HIV coinfection portfolio studies.
- Phase 2 trial of Sutezolid for improving sputum conversion at 8 weeks is in development pending drug availability.
- Phase 3 trial of rifapentine + moxi to shorten TB therapy to 4 months (with TBTC) pending site regulatory approvals.
- Early bactericidal activity of high-dose INH in patients with MDR TB and inha mutations are enrolling (131/198).
NIAID - Host-Directed TherapyRichard HafnerAn overview of TB host-directed therapy rationale, possible benefits, and specific examples of first-generation HDT agents and candidate agents for next generation HDT. Information is also provided regarding application of precision medicine approaches to TB therapy.
- Simvastatin increases the in vivo activity of the first-line tuberculosis regimen.
- Next generation HDT agents will be targeted agents chosen to reverse specific abnormalities caused by Mtb in cell regulatory pathways of infected/immune reactive cells and immune effector functions of immune reactive cells.
- Adjunctive treatment with metformin and with imatinib have also increased activity against Mtb in animal models.
- These precision medicine approaches to reverse immunosuppressive mechanisms of Mtb may be also applied to potentiate responses to TB vaccines.
- Leveraging the exciting advances in precision medicine for the development of innovative next-generation HDTs may lead to entirely new paradigms for treatment and prevention of tuberculosis and other infectious diseases.
University of Munich / EDCTP / PanACEAMartin BoereeMichael HoelscherOverview of high dose rifampicin 1 and 2 studies: design, results and conclusions. PanACEA MAMS-TB-01 with evaluation of HDR35, SQ109 & R20moxifloxacin: trial study design, results and conclusions.
- The HIGHRIF 1 study resulted in good safety and tolerability in dose escalating small groups up to 40 mg/kg, together with an increase in PK parameters and fall in bacterial load.
- The HIGHRIF 2 study resulted in no differences in safety and tolerability in the three groups (600, 900, 1200 mg).
- High-Dose Rifampicin is well tolerated; 20 mg/kg is probably too low. 35mg/kg has an increased effect in time to culture conversion.
- In the MAMS trial the arms containing SQ109 had no increased effect in this design.
View Boeree's SynopsisOverview of PanACEA studies pipeline, drug targets, mechanism of action, efficacy and timeline.
- Mission of PanACEA Studies is to identify novel regimen that have a high potential to shorten and simplify the treatment of tuberculosis.
- Q203 will complete Phase 1 SAD and MAD in 2016.
- BTZ043 will submit IMPD in 2016 and start phase I in 2017.
View Hoelscher's SynopsisTB Trials Consortium (CDC)Neil SchlugerOverview of the TBTC mission, trial consortium, pipeline, and study results.
- The mission of the TBTC is to conduct programmatically relevant clinical, laboratory and epidemiologic research concerning the diagnosis, clinical management, and prevention of tuberculosis infection and disease.
- Higher rifapentine doses are needed in children to achieve therapeutically important AUC.
- Risk factors for hepatotoxicity in a large LTBI treatment trial.
- TBTC rifapentine program Phase 3 clinical trial of shortened treatment regimen now enrolling.
Final Agenda