TRIC-TB

Boosting Ethionamide efficacy and lowering the dose with a small molecule transcriptional modulators, to overcoming MDR-TB infections and define a new place for Ethionamide in 1st-line TB treatments

Summary

Tuberculosis is a major public health threat. In 2017 alone, over 10 million people developed active TB and it killed 1.7 million, making it one of the top 10 causes of death worldwide. Treatment is via a six-month course of four antibiotics. Drug resistance is a major issue in TB – in 2017, over half a million drug-resistant cases were recorded, and most of these (82 %) were multi-drug resistant (MDR); these cases are much harder to treat successfully.

The aim of TRIC-TB is to advance the development of two molecules that could boost the infection-fighting ability of the anti-TB drug Ethionamide. The compounds, BVL-GSK038 and BVL-GSK098, work by interfering with the systems that control gene activity in the TB bacteria. Previous studies have shown that they are able to boost the efficacy of Ethionamide three-fold.

If the results are confirmed in humans, this could allow doctors to reduce the dose of Ethionamide typically given to patients, something that would also reduce the side effects associated with the drug. Moreover, it appears that BVL-GSK038 and BVL-GSK098 overcome some of the mechanisms that the TB bug has developed against Ethionamide.

TRIC-TB will carry out further research in areas such as safety, mechanism of action, and potential synergies with other drugs; if these go well, the team will carry out the first clinical studies in humans of these potential drugs.

Ultimately, the information delivered from this research will hopefully allow the new compounds to be integrated into new, improved regimens to treat TB, including MDR-TB.

TRIC-TB is part of the IMI AMR Accelerator Programme.

Achievements & News

TRIC-TB starts clinical trial of anti-TB drug booster

The TRIC-TB project has started a clinical trial with BVL-GSK098, a drug that is designed to boost the infection-fighting ability of the tuberculosis (TB) drugs ethionamide (Eto) and prothionamide (Pto). ###Although Eto and Pto are potent weapons in the fight against TB, they can cause severe side effects. If approved for use, BVL-GSK098 could allow doctors to reduce the efficacious dose of Eto or Pto, and along with it the side effects they cause. Importantly, BVL-GSK098 has shown in preclinical studies to overcome pre-existing resistance to Eto and is active against multi-drug resistant (MDR)-TB.

Last year, the US Food and Drug Administration (FDA) gave Qualified Infectious Disease Product (QIDP) designation to BVL-GSK098 in a fixed combination with Eto, a move that incentivises clinical development with faster development times, by allowing for fast track and priority review designations, and offers 5 years of additional market exclusivity in the USA.

Now, BioVersys, the Swiss SME behind the drug, has announced the start of a Phase 1 clinical trial of BVL-GSK098 in collaboration with GSK. The trial, which involves healthy volunteers, aims to assess the safety and tolerability of BVL-GSK098 as well as its behaviour in the body.

‘More than 1.5 million people die every year from tuberculosis through a lack of efficacious treatments and access to medicines,’ said BioVersys CEO and co-founder Dr Marc Gitzinger. ‘At BioVersys we remain committed to developing innovative and life-saving treatments for patients suffering from drug-resistant infections, and the combination of BVL-GSK098 and Eto or Pto has the potential to improve patient outcomes, reduce treatment times, and even replace isoniazid in first-line TB therapy.’

‘GSK is committed to the discovery of novel treatments for tuberculosis including the drug-resistant forms of Mycobacterium tuberculosis,’ said Dr David Barros-Aguirre, VP and Head of Global Health Pharma Research Unit, Global Health Pharma R&D, GSK. ‘Entering clinical trials is an important milestone in our successful collaboration with BioVersys as we develop BVL-GSK098 within the IMI2 TRIC-TB programme, towards a potential treatment to optimise the beneficial effects of ethionamide.’

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Regulatory decision gives boost to development of potential new TB drug

A decision by US regulators is set to speed up reviews of a potential new TB drug being developed by IMI’s TRIC-TB project.###

Tuberculosis is a major public health threat. In 2017 alone, over 10 million people developed active TB and it killed 1.7 million, making it one of the top 10 causes of death worldwide. Treatment is via a six-month course of four antibiotics.

IMI’s TRIC-TB project was set up to advance the development of molecules that could boost the infection-fighting ability of the anti-TB drug Ethionamide. Now, the US Food and Drug Administration (FDA) has given Qualified Infectious Disease Product (QIDP) designation to one of the compounds (BVL-GSK098) in a fixed combination with Ethionamide for the treatment of pulmonary TB.

QIDP designation is given to antibacterial or antifungal drugs designed to treat serious or life-threatening infections. Crucially, QIDPs are eligible for priority and fast track review by the FDA. This will therefore help TRIC-TB to speed up the development of the compound.

Ultimately, if clinical trials are successful, BVL-GSK098 could allow doctors to reduce the dose of Ethionamide typically given to patients, something that would also reduce the side effects associated with the drug.

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Participants

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EFPIA companies
  • Glaxosmithkline Investigacion Y Desarrollo SL, Tres Cantos, Spain
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
  • Bioversys AG, Basel, Switzerland
Third parties
  • BioVersys SAS, Lille, France

Participants
NameIHI funding in €
Bioversys AG6 813 875
 
Third parties
NameFunding in €
BioVersys SAS112 500
 
Total Cost6 926 375