Gathering momentum to tackle antimicrobial resistance

Rebecca Aris interviews Dr John Rex

AstraZeneca

We interview Dr John Rex, VP Clinical Infection at AstraZeneca for an update on the Innovative Medicines Initiative’s NewDrugs4BadBugs programme, which focuses on antimicrobial resistance.

Following on from our recent blog post by Dr John Rex we interview him for an update on the Innovative Medicines Initiative’s NewDrugs4BadBugs programme.

We discuss the problem posed by antimicrobial resistance, and what other therapeutic areas could benefit from a collaborative approach such as the NewDrugs4BadBugs programme.

Interview summary

RA: Doctor Rex thank you for joining us today. You recently wrote a blog post on pharmaphorum on the NewDrugs4BadBugs programme, for those that don’t know about the programme could you please start by explaining it?

JR: NewDrugs4BadBugs is a collaboration that was initiated by the Innovative Medicines Initiative, sponsored over the past several years by the European Commission. The Innovative Medicines Initiative has put together a series of collaborative activities with NewDrugs4BadBugs being their most recent one, which is focused on antimicrobial resistance. A number of pharmaceutical firms besides AstraZeneca, GSK, Janssen, Sanofi, and Basilea are partnering on this programme, and there may well be other partners joining in the future.

The programme was developed collaboratively with the European Commission as part of their action plan against rising threats from antimicrobial resistance.

It’s been several years coming as it takes a while to build these things up, but at this point we have a serious collaboration. The focus of the programme will be on designing clinical trials, taking novel drug candidates through clinical development, and trying to find new drugs. It’s quite a broad reaching and really ground-breaking approach to working together across industry.

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“It’s quite a broad reaching and really ground-breaking approach to working together across industry.”

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RA: What’s driven increasing bacterial resistance, and why has it become such a big problem?

JR: The use of antibiotics. The good news is that there has never been a class of drugs more potent in terms of saving lives than antibiotics. An antibiotic can take a child with bacterial meningitis and cure them, giving him or her 60 years of life back. But every time you use an antibiotic, you have the risk of developing resistance to them. Bacteria develop resistance steadily, so we need a steady stream of new antimicrobial agents to respond to it. In addition, we need to use the ones we have very thoughtfully.

There’s a lot of discussion about the need for antibiotic stewardship, which doesn’t mean not using them, it means using them effectively.

Antimicrobial resistance is a major public health threat that affects everybody. Anybody at any time is potentially at risk for a resistant bacterial infection. Frustratingly, during the past three decades, there have only been two new classes of antibiotics found. Why are there so few new drugs? It’s just hard to find them. Discovering new antibiotics is scientifically relatively difficult in large part because antibiotics are one of only two classes of drugs that are designed to kill things, the other class being cancer drugs. When you’re trying to kill a target you need more of a drug than you do when all you’re trying to do is gently tweak an existing system. Therapies for things, such as hypertension and lipid disorders, are drugs that just very gently tweak an existing human system. Antibiotics are trying to kill something, and that produces an interesting set of scientific challenges.

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“Bacteria develop resistance steadily, so we need a steady stream of new antimicrobial agents to respond to it.”

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RA: What are you hoping to achieve with this programme?

JR: Fundamentally it’s about creating momentum. This is a very difficult problem, and by working together we are more likely to solve it. Working together creates an energy that you can’t get in any other way. The unique aspect of this is the information sharing among the partners, we’re going to share information in ways we never have. We are responding to the European strategy to combat antimicrobial resistance, but really we’re doing it for the world. It’s going to cover the entire waterfront of drug-resistant pathogens, both Gram-negative and Gram-positive organisms. You don’t know which part of this programme will be the most successful, but putting it all together like this is going to generate a level of that energy we’ve never seen before.

RA: Are we not ultimately fighting a losing battle, can new drugs really keep up with the resistant bacteria?

JR: I actually think that we can keep up. The need for innovative medicines is an issue, but also there are new drugs emerging and really advanced rapid diagnostic tools that would support our ability, or enable us to use both old and new drugs more effectively to reduce the pace of development of resistance.

So while this is a crisis, the good news is that we are doing something to tackle the problem. We now have a multi-stakeholder approach with the innovative medicines initiative.

We’re seeing similar things beginning to happen in the United States, so we’re going to continue to progress.

AstraZeneca has long recognised the need to work in this area, and we’re still here, we’re a big company working on this problem, so I remain hopeful.

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“Why are there so few new drugs? It’s just hard to find them.”

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RA: What are the advantages in involving so many organisations, and what do they each bring?

JR: Teamwork and creating momentum. Really complex problems are almost always best addressed by teams. We’re looking for lots of people to get involved in this multi-stakeholder attack on the complex critical issues.

The regulatory process needs to be augmented, there are gaps in the current regulatory paradigm that need to be addressed. The energy of NewDrugs4BadBugs will encourage regulatory evolution over time. The European Medicines Agency recently released a draft addendum to its development guidelines for antibacterials that include some forward looking thinking that is going to make a big difference.

The other challenge for antibiotic developers is the economics of the area, which is also something that NewDrugs4BadBugs may tackle with a multi-stakeholder conversation. The first version of NewDrugs4BadBugs did not include a specific work package on this topic, but we’re currently discussing adding one to an extension of NewDrugs4BadBugs.

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“Antibiotics are trying to kill something, and that produces an interesting set of scientific challenges.”

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RA: What other therapeutic areas do you think will benefit from such collaborations?

JR: Any area with a big complex problem will benefit from collaborations. An area that has been in the news lately and which looks like collaborations are the way of the future is neuroscience. AstraZeneca has been heavily involved in converting its internal neuroscience efforts into an external or a virtually-based highly-collaborative neuroscience model. We recently announced ‘the A5 collaboration’, which is AstraZeneca partnering with four academic institutions in Alzheimer’s disease, so it’s A for Alzheimer’s and five for the number of research organisations involved.

Neuroscience is recognised as an area that’s incredibly complex. Alzheimer’s is a disease that probably has multiple underlying causes, which drives the need for collaboration.

RA: What do you think the area of infectious diseases will look like in 10 years’ time?

JR: At the simplest level we will continue to see resistance, and a need to collaborate. I hope that we will see new drugs available and the ready availability of diagnostic tools. We’re definitely going to see new regulatory pathways that enable new drugs to get developed well in advance of the need for them becoming as acute as we currently are right now.

Right now we are behind the curve. We need the drugs now and it’s going to take some years before we have them. We want to avoid repeating that situation, we want to be able to develop drugs well in advance of the full-blown need for them.

So I think that’s going to be the difference, new drugs, new tools, and ongoing collaborations that are keeping us ahead of the crisis.

RA: Doctor Rex thank you very much for your time and for your insights.

JR: Thank you.

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About the Innovative Medicines Initiative (IMI):

The Innovative Medicines Initiative Joint Undertaking (IMI JU) is a unique pan-European public private partnership between the European Commission and EFPIA (European Federation of Pharmaceutical Industries and Associations) driving collaboration between all relevant stakeholders including large and small biopharmaceutical and healthcare companies, regulators, academia, and patients.

The aim of IMI is to propose a coordinated approach to overcome identified research bottlenecks in the drug development process, in order to accelerate the development of safe and more effective medicines for patients, by fostering collaboration between all stakeholders such as industry, public authorities (including regulators), organisations of patients, academia and clinical centres, and enhancing Europe’s competitiveness.

The revised IMI Scientific Research Agenda describes the research bottlenecks in the drug development process and identifies new and established research priorities correlated to at least one of the seven IMI Areas of Research Interest. The IMI 6th Call 2012 for proposals consists of one theme: Combating Antibiotic Resistance: NewDrugs4BadBugs (ND4BB), which falls under one of the new key research priorities: ‘infectious diseases’, which is correlated to the following Area of Interest: Disease Drug Efficacy.

About AstraZeneca:

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit: http://www.astrazeneca.com/.

Can new drugs really keep up with resistant bacteria?