AMR – a global public health emergency
Antimicrobial resistance is a major threat to public health worldwide. In Europe alone, AMR kills an estimated 33 000 people annually. Globally, it kills 700 000 every year and that figure is set to rise to 10 million by 2050. There is therefore an urgent need for new medicines to prevent and treat resistant infections. In its 2017 action plan on AMR, the European Commission includes a chapter dedicated to boosting research, development and innovation which cites IMI as one of the tools to be used to address AMR.
Introducing the IMI AMR Accelerator
IMI launched the AMR Accelerator in 2018 as part of IMI2 – Calls 15 and 16; two additional AMR Accelerator topics were launched in 2020 as part of IMI2 - Call 20 and IMI2 - Call 23. The goal of the programme is to progress the development of new medicines to treat or even prevent resistant bacterial infections in Europe and worldwide. The programme has three pillars: a Capability Building Network, a Tuberculosis Drug Development Network; and Portfolio Building Networks. The scope of the AMR Accelerator is broad; under one structure, it addresses many of the scientific challenges of AMR, and it supports the development of new ways to prevent and treat AMR (including new antibiotics).
Within this broad scope, projects in the AMR Accelerator will develop new pre-clinical tools and methods, validate alternative or ‘non-traditional’ approaches, progress potential new treatments through phase 1-3 clinical trials, and analyse data from EFPIA-funded clinical trials to assist in the translation of preclinical data to clinical results of novel anti-infective agents. As such, the AMR Accelerator complements and builds on the achievements of IMI’s New Drugs for Bad Bugs programme, which also focuses on AMR.
Pillar A: Capability Building Network (CBN) to accelerate and validate scientific discoveries
The Capability Building Network comprises two projects: COMBINE and PRIMAVERA. COMBINE was created to coordinate the AMR Accelerator projects and provide them with the resources they need to achieve their goals. These include data management guidelines and an IT infrastructure to enable the collection, aggregation, storage, sharing and analysis of datasets generated by AMR Accelerator projects. COMBINE will also help to ensure that data adheres to ‘FAIR’ principles, i.e. it is findable, accessible, interoperable, and re-useable. Promoting communication among the projects is another COMBINE priority.
On the scientific front, COMBINE aims to improve the animal models used in AMR research and develop improved tools to reliably translate results in animals into results in humans. The project also aims to optimise the design and analysis of clinical trials. These tools will help all projects in the programme to deliver results that will help to accelerate the development of novel antibiotics and vaccines against AMR.
PRIMAVERA focuses on vaccines and monoclonal antibodies (mAbs, laboratory-made antibodies similar to those your body makes in response to an infection). Vaccines and mAbs could play a key role in the fight against AMR, but their development is constly and time consuming, so choices need to be made on what should be prioritised for development. The aim of PRIMAVERA is to develop mathematical models and an epidemiological repository that will facilitate the assessment of different vaccines and mAbs in terms of their likely impact on AMR. PRIMAVERA will set up an open access, web-based platform that will allow the wider scientific and healthcare communities to freely access and use the models and repository.
- COMBINE | Collaboration for prevention and treatment of MDR [multi-drug resistant] bacterial infections
- PRIMAVERA | Predicting the impact of monoclonal antibodies & vaccines on antimicrobial resistance
Pillar B: Tuberculosis Drug Development Network (TBDDN) to accelerate and validate scientific discoveries and advance the R&D pipeline of new and innovative agents to address the global TB epidemic
As its name suggests, the Tuberculosis Drug Development Network is working to accelerate the discovery of new combinations of drugs to treat TB. Treating TB involves regimens of a number of drugs, and as new drugs are added to regimens one by one, building a new, faster and safer treatment regimen takes a very long time. The ERA4TB project plans to drop the sequential approach and instead adopt a parallel pathway, which will allow the project to investigate the safety and efficacy of combinations of over a dozen drug candidates at the same time. Concretely, the project aims to create a world-class ‘platform’ that brings together the expertise, tools and resources needed to accelerate the development of anti-TB drug combinations. The hope is that the platform will continue to operate beyond the end of the project.
Meanwhile the UNITE4TB project aims to accelerate and improve clinical trials of combinations of existing and new drugs, with the goal of developing new and highly active treatment regimens for TB, including drug-resistant TB. In the long term, these regimens could ultimately become the global gold-standard for TB treatment, and so contribute to the goals of the World Health Organization’s End TB programme.
- ERA4TB | European regimen accelerator for tuberculosis
- UNITE4TB | Academia and industry united innovation and treatment for tuberculosis
Pillar C: Portfolio Building Networks (PBN) to advance the R&D pipeline of new and innovative agents to address AMR
The Portfolio Building Networks support collaborative efforts to discover, develop and advance new and innovative agents to prevent or treat AMR. PBNs provide a mechanism for dedicated partnerships between EFPIA companies and small and medium-sized enterprises (SMEs) and/or academic teams for the discovery and development of new antibacterial assets. Assets and projects can originate from SMEs, academia, or EFPIA companies, and will be jointly progressed or studied, including both pre-clinical work and potentially phase 1-3 clinical development.
- AB-DIRECT | Antibiotic distribution and recovery in tissue
- GNA NOW | Novel Gram-negative antibiotic now
- RespiriNTM | Progress novel assets (one FIH [first in human] start) for non-tubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs
- RespiriTB | Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors
- TRIC-TB | Boosting ethionamide efficacy and lowering the dose with a small molecule transcriptional modulators, to overcoming MDR-TB [multi-drug resistant tuberculosis] infections and define a new place for ethionamide in 1st-line TB treatments
Achievements & News
UNITE4TB explored how low- and middle-income countries can roll out the molecular diagnostic tests needed to determine the best course...
Laboratory studies show that a potential antibiotic dubbed NOSO-502 is active against some of the most dangerous drug-resistant bacteria. The...
IMI tuberculosis project TRIC-TB is using a novel approach to boost the efficacy of existing TB drugs.
IMI Associated Partner TB Alliance is a non-profit organisation whose mission is the discovery, development and delivery of new and affordable tuberculosis (TB) drugs. In an interview with the IMI Programme Office, Director of External Affairs Ana Maria Harkins says that the partnership with IMI allows them to expand funding beyond a small and mostly static group of donors.###
‘As a product development partnership, we leverage public-private mechanisms to accomplish our work, and the IMI model aligns well with our way of working,’ says Ms Harkin. ‘IMI brings together many of the main players and we greatly value the resources it makes available, as well as a platform to collaborate with industry, academia and the public sector.’
TB Alliance is involved in two IMI projects. Through ERA4TB, they are contributing two compounds for development, one of which is in Phase 1 trial. In EU-PEARL, they are involved in the work package dedicated to TB, where they provide regulatory expertise, knowledge and tools for community and patient engagement.
Asked about the benefits of working in a public-private partnership, Ms Harkin highlights the importance of tackling market failures like antimicrobial resistance. ‘Without political and financial incentives, the industry has little incentive to develop antibiotics,’ she says. ‘IMI provides resources to incentivise drug development, and an architecture that brings together an array of partners to contribute compounds, perform preclinical and clinical work, exchange data and research learnings and jointly work towards a set of agreed-upon outcomes.’
Find out more
- Read the interview in full
IMI’s GNA NOW project is looking for a novel antibiotic programme to progress to Investigational New Drug (IND). The deadline for expressions of interest is 18 June.###
The aim of GNA NOW is to advance the development of antibiotics designed to treat infections caused by Gram-negative bacteria. These bugs are particularly tough to treat, as they are encased in a tough outer membrane which effectively stops many antibiotics from getting into the bacteria and killing it.
Now the project has launched a call for expressions of interest for potential antibiotics with a novel mode of action designed to address severe hospital infections caused by certain drug-resistant, Gram-negative bacteria.
Those interested in getting involved should submit a short, non-confidential submission of interest to the project by 18 June. Expressions of interest will be assessed by the GNA NOW Review Committee, which is made up of industry, independent and academic experts and antibiotic drug discovery and development.
The teams behind the top three expressions of interest will then be invited to submit a full dossier to the committee.
Find out more
- Read the article in full
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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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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Antimicrobial resistance (AMR) is becoming one of the defining problems of our time. As bacteria become resistant to the drugs that are supposed to kill them, scientists, policy makers and the pharma industry are looking at different ways to fix the problem before it’s too late. IMI has invested heavily in AMR research. ###To date, we have invested almost €800 million on 14 projects. Throughout November, we turned the spotlight on some of IMI’s projects in this area and explored the different angles from which they’re tackling the problem.
Read the articles
- Focus on AMR
- New antibiotics won't stop AMR. Luckily, there are other things we can try. – editorial by Pierre Meulien, IMI Executive Director
- Why it's so hard to make new antibiotics
- A very promising antibiotic just started clinical trials
- Technology, not instinct, should guide antibiotic prescribing
Antimicrobial resistance (AMR) is becoming one of the defining problems of our time. As bacteria become resistant to the drugs that are supposed to kill them, scientists, policy makers and the pharmaceutical industry are looking at different ways to fix the problem before it’s too late. IMI has invested heavily in AMR research.### In November, we will be taking a look at some IMI projects and the different angles from which they’re tackling the problem – from rapid diagnostics and public health policy, to permeability and prophylactic vaccines.
Find out more about IMI’s AMR projects:
Details of all project participants can be found on the individual project factsheets.