The Stop TB Partnership Working Group on New Drugs’ Annual Meeting has proven valuable as a neutral forum to bring together those working in development to get a full understanding of the progress, challenges, and critical issues to developing TB treatment.
The 2017 WGND Annual Meeting and Lunch took place on Wednesday, October 11th from 09:00 to 01:00 at the Hilton Guadalajara. The meeting took place in conjunction with this year's Union World Conference on Lung Health in Guadalajara, Mexico.
During the meeting, updates were provided on the most recent advances in the Global TB Drug Pipeline, current opportunities for progressing TB drug candidates into late-stage clinical trials, and other important news in TB drug development.
- From the Working Group on New DrugsWGND UpdatesCherise ScottZaid Tanvir
Updates from the WGND include greater collaboration with new tools working groups, developing advocacy messages for high-level TB meetings, and tracking Global Plan progress. Activities in 2017 have included updating WGND TOR, WGND website, convening drug developers at the 2017 GRC TB Drug Discovery & Development for a workshop, and producing a review article on host-directed therapies. Upcoming in 2018 are further improving valuable resources, sponsoring meeting/expert panels, producing more online content in the form of a podcast, and continuing to contribute research messages.https://www.newtbdrugs.org/sites/default/files/meetings/files/01_WGND_CScott_2017.pdfTB Drug Development Year-in-ReviewBarbara Laughon
The WGND Pipeline has been updated with significant advances for many TB drug trials and compounds. This includes 6 advances in Phase 3/Registration, 7 advances in Phase 2, 6 advances in Phase 1, and 7 advances in TB drug discovery. Updates were made to the WGND Pipeline PowerPoint available on the WGND website; including added slides for identifying drug targets and a slide on TB drug regimen clinical research.https://www.newtbdrugs.org/sites/default/files/meetings/files/02_%20Laughon%20Year%20in%20Review.pdf
- Early-Stage DevelopmentSanofiBrigitte Demers
Sanofi’s strategy for TB treatment include a joint & complementary effort in the frame of various partnerships for improvement of treatment of both TB infection and disease. Sanofi utilizes a novel target candidate profile to tackle DR-TB (with a new mechanism of action) and to substantially reduce treatment duration for both DS-TB and DR-TB (sterilizing drugs). Sanofi’s two most advanced series are the Griselimycins and Sequanamycin macrolides, which are both in pre-candidate selection.https://www.newtbdrugs.org/sites/default/files/meetings/files/03_%20WGND%20Annual%20Meeting%20Guadalajara%202017%20-%20Sanofi%20B.Demers%20Revisited.pdfGSKDavid Barros
GSK is currently involved in development or collaboration for a full portfolio of TB drug candidates. Collaborators include EDCTP, imi, Horizon, and BMGF. This presentation characterizes the following candidates: GSK3030656 (a MTb LeuRS inhibitor involved in protein synthesis); GSK2556286 (MOA selectively kills intracellular Mtb); and ETH boosters (potentiating ethionamide activity).https://www.newtbdrugs.org/sites/default/files/meetings/files/04_WGND%20GSK%20david%20barros.pdf
- Multi-Stage DevelopmentOtsukaRajesh Gupta
Otsuka characterizes their FighTBack Strategy which includes innovative research and development; responsible access to patients; optimized patient management; and collaborative capacity building. As of October 2017, over 4,400 courses of Delamanid have been supplied as part of expanded access, compassionate use, or under normal programmatic conditions. Results from Delamanid Compassionate Use Early Outcomes, Japan Early Outcomes, Latvia Final Outcomes, Bedaquiline and Delamanid Combination Treatment and pediatric studies are presented, along with other studies. The second Otsuka anti-TB compound, OPC-167832 has nearly completed its single ascending dose study and a multiple ascending dose/EBA study in TB patients is scheduled to start in Q4 2018.https://www.newtbdrugs.org/sites/default/files/meetings/files/05_WGND%20Annual%20Meeting%20Otsuka%202017%20revised.pdfTB AlliancePaul Bruinenberg
TB Alliance’s goal is to develop a novel molecule TBA-7371 (an inhibitor of DprE1- needed for MTB cell wall biosynthesis) which has the potential to shorten the treatment of all forms of TB as part of a universal regimen. Compound TBA-7371 is full characterized. TB Alliance has completed safety pharmacology, genotoxicity, 1-month rat toxicity, 1-month monkey toxicity and CMC activities for Sutezolid. GLP safety Pharmacology and the Phase 1 study design rationale is provided.https://www.newtbdrugs.org/sites/default/files/meetings/files/06_WGND%20Phase%201%20TBAG%20PBruinenberg%20Union%202017%20F.pdf
- Mid-Stage DevelopmentTB-PractecalBern-Thomas Nyang'wa
The goals of TB Practecal are to identify a new regimen(s) for DR-TB that is radically shorter, tolerable, effective and feasible to scale up through an ICH-GCP trial and to target WHO policy change. Trial has a multi arm, multi stage design involving a seamless transition between phases II and III. 40 recruited in one active of four planned trial sites as of October 2017. The trial involves three sub studies.https://www.newtbdrugs.org/sites/default/files/meetings/files/07_TB-PRACTECAL_%20WGNTD_Guadarajara.pdfSequellaDavid McNeeley
Sequella is currently developing SQ109 for tuberculosis treatment. Human metabolism, EBA, clinical pharmacokinetics, and MAMS trials are reviewed. Conclusions from these studies include: RIF is now known to decrease exposure of SQ109, SQ109 is likely to be sterilizing rather than bactericidal, and SQ109 may be best assessed in an MDR-TB population without RIF. The Russian SQ109 trial in MDR-TB patients reports a positive outcome and adds to the human experience with SQ109 (3 Phase 1 studies and 3 Phase 2 trials) with no drug-related Serious Adverse Events (SAE) in 345 healthy individuals or TB patientshttps://www.newtbdrugs.org/sites/default/files/meetings/files/08_WGND%20SQ109%20Oct%202017%282%29%20Final.pdfPanACEANorbert Heinrich
PanACEA’s work plan involves a full portfolio of TB drug candidates. Development updates with BTZ-043 (inhibitor of DprE1) involve discussion on mouse models, safety, and Phase 1 preparations. For Q203, the dose escalation is ongoing. Phase 2a study protocol under review by regulatory (MCC). High RIF update include MTD study resuming enrollment, RIF dose-exposure-respond model submitted for publication, and MAMS sub-analysis on RIF dosages nearing completion.https://www.newtbdrugs.org/sites/default/files/meetings/files/09_WGND%20PanACEA%20Heinrich.pdf
- Late-Stage DevelopmentendTBLorenzo Guglielmetti
The endTB trial, which is funded by Unitaid and includes MSF, IRD and Partners in Health as consortium partners is expected to take 4 years. The objective is to design future regimens for MDR TB. endTB Trial summary, objectives, study population, and endpoints are characterized. Two associated substudies will occur with funding from Wellcome Trust.https://www.newtbdrugs.org/sites/default/files/meetings/files/10_endTB_WGND_Union17_final.pdfJanssenTine DeMarez
Overview of Bedaquiline’s public health impact, clinical development program, regulatory status as of October 2017. As of August 2017, over 32,000 cumulative treatments delivered to 85+ countries. Janssen’s Pediatrics C211 Trial design is characterized and an overview of Bedaquiline-containing regimens currently being studied is provided.https://www.newtbdrugs.org/sites/default/files/meetings/files/11_WGND2017.pdf
- Drug Development OpportunitiesLife PrizeGrania Brigden
The Life Prize’s mission is to rapidly deliver an affordable, short-course treatment regimen effective against all forms of tuberculosis. To achieve this the Life Prize consists of prize funding for drugs entering clinical trials that fulfil predefined criteria and additional grant funding to finance the development of a pan-TB regimen in line with target regimen profiles. Presentation describes the incentives, procedure and the target drug developers/funders involved.https://www.newtbdrugs.org/sites/default/files/meetings/files/12_%20The%20Life%20Prize%20WGND%20meeting%20October%202017.pdf