Saving the shrinking pipeline for antibiotics

Nov. 16, 2020

The threat of superbugs hasn’t gone away and in many ways the pandemic has made this problem loom even larger. But a new organization called the AMR Action Fund is working to infuse needed dollars and resources into the dwindling pipeline for needed antibiotics.


Meagan Parrish: Do you remember back before the pandemic hit when superbugs were the scariest Boogeyman in the health care world? I mean, of course, you do. But you'd be forgiven if you haven't thought about them in a while. These days, all the attention is on the Coronavirus. And importantly, so are the resources of the pharma industry, including research dollars, human power, and regulatory efforts, but superbugs haven't gone away. In fact, in many ways, the pandemic has made this threat loom even larger.

I'm Meagan Parrish, senior editor of Pharma Manufacturing Magazine, and you're listening to Off Script, our podcast that runs beyond the pages of our magazine to discuss the issues that matter most in the pharma world.

Now, we've known about superbugs for a long time, and the predictions about what the spread of a life-threatening bacteria that's resistant to antibiotics could do have long been ominous. Some have called this threat potentially the end of modern medicine or sounded the alarm about an antibiotic apocalypse. We've also long known that because antibiotics are considered commodities, there's not much return for pharma companies investing in innovative new options. So, R&D dollars for new antibiotics have been drying up year after year. Now, here's a quick snapshot of how this issue has been impacted by the Coronavirus. The unneeded use of antibiotics is on the rise, which we know exacerbates the problem of microbes building a resistance to them.

One study showed that between May and June of this year, about 56% of 1,700 Coronavirus patients in Michigan were given antibiotics even though only 3.5% were shown to have a confirmed bacterial infection. But for Coronavirus patients that do indeed have a bacterial infection, the outcome worsens especially in critically ill patients. According to research published by the American Society of Microbiology, what's even more concerning is the fact that a higher rate of bacterial co-infections occurred in critically ill patients even though a vast majority of them or 92% in this study were given antibiotics. But worst of all, in this study, there were 28 patients who are critically ill and developed a secondary bacterial infection, and all but one of them died.

Despite these very troubling reports, there is some hope in the market for new antibiotics to fight superbugs. For example, new regulatory and market efficiencies that have been created to speed the development of Coronavirus vaccines and treatments could also potentially be applied to a new race for antibiotics. And a new organization was launched this year to help infuse the pipeline for new antibiotics with needed cash and resources called the AMR Action Fund. The group is being backed by a number of major pharma companies and has secured investments for antibiotics totaling up to $1 billion.

So, to help give us more of an idea about what the AMR Action Fund is all about, and what impact it could have on the market for antibiotics, I'm joined today by Martin Bott, the organization's Interim General Manager. Martin also spent over 30 years at Eli Lilly & Co. as a vice president of finance and special projects and more. Okay, Martin. Thank you so much for joining me today to talk about this really important issue.

Martin Bott: My pleasure. Thank you for having me.

Meagan: Absolutely. I was wondering if we could start by having you just give me a little bit of background on the AMR Action Fund and how it came about?

Martin: Yeah, perhaps I'll start with what is antimicrobial resistance? That's, you know, some people call it the superbugs and so forth. And that is really an existing and a growing public health needs. So I mean, estimates right now are that about 700,000 people die every year of bacterial infections that cannot be treated. And the trend is not very encouraging, and some predictions if the current trends continue by 2050, it could kill as many as 10 million people, more than currently die of cancer. This has led really the pharmaceutical industry and under the leadership of the International Pharmaceutical Association in 2019, so that's actually before we all heard about COVID-19 to step back and say how can we play a role in addressing this public health need? Major issue is that there have been very little innovation in novel antibiotics.

I read some somewhere that the last novel class of antibiotics was brought to market in the 1980s, so that's a long time ago. And the root cause of that, in my opinion, is that the market has somewhere failed to recognize the value new antibiotics bring to people and to society at large and therefore, risk capital has not come into this area to encourage and fund risky research and development. And so that's where we're trying to address here. This fund is mainly sponsored by the industry to help bring forward novel, very promising signs, and antibiotics so that we can save people's lives.

Meagan: Yeah, and you mentioned that it's funded by the industry. Can you explain that a little bit more?

Martin: Yeah. So, to date, and we announced in July, more than 20 pharmaceutical companies have taken the initiative and come together with so far, almost $1 billion to create this fund. We also do expect to get additional investors both from the industry and non-industry, and they could be coming from philanthropic and charitable organizations, development banks, and so forth. So, ultimately, when it's all said and done, we hope and expect to have a fund of a size of more or more than a billion dollars ordered. Interesting to note is that the companies that come together of all sizes, geographically from every corner of the world, Japan, Europe, U.S., and so forth. Large small companies, companies that are still active in this field, some are not in this field.

And the purpose really is to take this money and invest it where the most pressing needs are, and that is when we see good science coming out of preclinical going into early clinical trials, that can really make a difference in clinical practice and save people's lives. Let's make sure that none of that innovation gets stuck due to lack of funding. And so the industry wants to lend its dollars as well as its talent, its expertise to help this bring to market. However, this is just a short-term fix, and we also need to make sure that different reimbursement systems are being put in place so that we put in place a sustainable ecosystem that rewards risk capital and the investment of talent and money into research and develop antibiotics so that we can actually solve this challenge against the superbugs for decades to come and not just for the 2030.

Meagan: Right. And you talked about at the beginning just how big the stakes are, just how many people are dying from this issue, and just how much worse it could get. The AMR Action Fund has stated that its goal is to bring two to four antibiotics to market by 2030. So, given how big this issue is, I'm wondering will that be enough?

Martin: Absolutely not. Clearly, this is a significant amount of money, but there are probably more opportunities than we could even fund for this. You know, just to give an example right now, I think there are about 700 vaccines and therapeutics in development for COVID-19, but if you look at the pipeline of antibiotics, right now there are only 40 in clinical development. So, that just gives you a little bit at the magnitude. If you look at approvals in the last several decades of cancer drugs versus antibiotics, it has come down and more cancer drugs are there. That indicates the market is not working, so, we need to do more. Clearly, the fund will have a positive impact on development, because hopefully, we put the dollars and the expertise wisely into promising research. But more needs to be done in order to solve it on a sustainable way.

There have been really good efforts done by CARB-X, European Investment Bank, WHO, REPAIR Impact Funds to help foster early research, preclinical research, so when it comes out of academia into early clinical trials that has created, it could early-stage pipeline, and the fund, we really want to make sure that what's coming out of that effort doesn't get stuck, gets rewarded. And then we hope, however, that the markets are being reestablished and we have a sustainable ecosystem.

Meagan: Right. I was wondering if you could just tell me what the trends have been in the pipeline for antibiotics just let's say over the last five to 10 years, I mean, have investments been falling or staying level?

Martin: Yeah, the investments in antibiotic development has been declining and fewer companies are also researching. And as I said before, and I sound like a broken record, the issue is the reward on the other side for that risk, for that time, dollars and talent that's being put in is not rewarded. The current reimbursement systems which work on price times volume, and sometimes these antibiotics ought to be put in reserves, so shouldn't drive much volume, and if you need to charge a high price, you have an access problem and so forth. So, that's where we need to have a rethinking in these reimbursement reforms. So, as I said, the investment in antibiotics has been declining again. Some efforts, and I mentioned them before CARB-X, Novo Holdings, REPAIR Impact Fund from BARDA, etc., they've really done a tremendous job in fostering this early research and supporting antibiotic development, etc. We want to make sure it doesn't get stuck. And then, of course, we need to have new classes in antibiotics in order to address these superbugs or these high priority pathogens at which we're running out of ammunition.

Meagan: And I wonder if you could tell me just a little bit about the pipeline, and how it looks right now, you mentioned that we need new classes, are you seeing some new classes of antibiotics in development?

Martin: Yeah, we actually believe that the preclinical antibiotic pipeline is very strong. Again, I have to give praise to BARDA and CARB-X, and so forth. As of May 2019, nature reviews identified 407 discovery in preclinical development projects, many of them represented potentially new classes, or new targets or new mechanism of action. So, that makes us very optimistic that once those come into the later phase of clinical trial, the fund is established and we have enough really good promising science that the Fund will invest in and help bring to market. And that's how we will opt to get to the two to four antibiotics to the patients to save patient's lives by the end of the decade.

Meagan: I'm just curious, can you tell me a little bit about some of the challenges involved with developing new antibiotics compared to other classes of drugs? Are there any challenges that are very unique to antibiotics? Or is it kind of follow the typical timeline and the typical challenges that we see with other kinds of treatments?

Martin: Yeah, I'm not the expert and I'm not a scientist in that field. But clearly, I understand that toxicology is a key issue, right? So you may have something that has efficacy against the pathogen, against the bacteria, but how do you make sure it doesn't attack the healthy microbiome in your system and side effects and so forth? My understanding is that most ideas die when you try them out in toxins before you even test them in patients and so forth. That's one unique specificity on antibiotics. Manufacturing can be a challenge, but I think we have that on many other therapeutic areas as well.

Meagan: Okay, so the issue is really incentives, like you talked about, and giving the right kinds of funds. I'm wondering now, how have things shifted since the start of the Coronavirus pandemic, there were so much of the industry's time and resources and funds now are all being funneled into ending this pandemic and how has that impacted the work of the AMR Action Fund in your efforts?

Martin: Yeah, it has affected it a bit. First, the initiative started way before COVID. Now, that we work together with the WHO and European Investment Bank, and the Welcome Trust we've done a lot of thinking out there before and leverage their thinking in this proposal net to the fund, etc. The direct impact on our project and on our fund was that instead of having meetings in one room where we get everybody together, everything was virtual, our lounge meetings in July were virtual and many of our investors are very focused on COVID right now, and so 'I cannot distract myself, I need to be focused on solving this issue,' which makes total sense.

Having said this, even so, this whole antimicrobial resistance was there before COVID, COVID actually put a new lens on it in a positive way in my mind. So, I think COVID has shown that investment and preparation, being better prepared, has an incredible benefit in terms of reduced patient suffering and reduced economic damage. And I think that will help actually in our mind getting the right decision-makers together to say, "Okay, we need to address this antimicrobial resistance public health issues as well and cannot be penny-wise and pound-foolish, and probably need to spend some more money and investment in getting prepared or operating globally, and so forth." The other thing is, unfortunately, COVID has found that nothing more than one in five hospitalized COVID patients actually develop a bacterial infection. And many have been told, actually, of the people who died didn't die necessarily directly of the COVID virus but of the infections they acquired. And there was another lesson learned here that we need to give our healthcare providers, those heroes on the front line, we need to give them more options, more ammunition to fight bacterial infection.

Meagan: Yeah, what you were saying before reminded me of one of those key takeaways I had from microeconomics 101 back in college, and that was the cost of prevention is always cheaper than the cost of cleanup and that's certainly, something that we're seeing with the Coronavirus pandemic. And I could see how that would spur people to be more motivated to make sure that we don't experience a pandemic with these bacterial infections. And so I could see what you're saying about balancing the challenges of resources being taken away, but also the motivation is there. And so I'd imagine at this point, too, you've got to be thinking about how to keep this momentum going even after the pandemic and making sure people don't forget these lessons that they're learning.

Martin: Absolutely. I think there's great learnings from COVID as well. I think what you're seeing right now in unprecedented speed and collaboration and openness about the communication, cooperation between industry regulators, politicians, and so forth. I think these learnings we need to take here as well and apply this to here. All of the viruses or the bugs, the superbugs, the bacteria, they don't stop at the nation's border, right? These are global issues, and therefore, we need to work together globally in a transparent way and collaborate. These are human issues and not German, French, American issues, right? Those are global public health issues, and I think we can take a lot of learnings out into new approaches into clinical trials to see can we be more innovative in this and compare that to the appropriate risk-benefit analysis to evaluate is it safe to approve a drug to make it available for wider-use, etc.? Because the benefit to public health is outweighing some of the remaining risk, etc. How do you monitor this? We have great data capturing abilities today, real-world evidence, etc. I think we can learn a lot of what we are doing on COVID and apply this to, in general, drug development out of antimicrobial drugs.

Meagan: Yeah, I'm glad that you brought that up because I wanted to ask you about what we've seen in terms of how regulators and the government have been able to streamline both the clinical trials process and now the approvals process for these Coronavirus vaccines and treatments. And I'm wondering, and I think everyone in the industry is wondering, are these sort of new methods going to be applied to lots of different drug classes and development? But are you thinking that this is something that could help with antibiotics and is this something you might be sort of pushing for?

Martin: Yeah, I hope so. I hope so at the right time, we take the learnings and say what are the ones you've just take out in a crisis situation and which are the ones that they should be incorporated into our daily lives how we evolve, evaluate, develop drugs, etc. I think the goals here, for our fund here, is really right now to speed up that innovation in this context as well. We want to collaborate with regulators etc. And the other objective for the fund, more longer-term is to slow down the resistance, right? And that that again, needs collaboration with governments, healthcare providers, the industry, patients, etc.

And, you know, diagnostics play as well and to be able to have faster, more tailored diagnostics so that the physician doesn't have to give based on the guess, a broad-spectrum antibiotic, but can perhaps be more tailored to that specific infection the patient has and the pathogen that caused an infection. So, there's a lot of things that I think we can learn directly or indirectly from COVID, and which can reduce the cost of developing therefore help the equation speed up things. And then but I always have to come back, there is also need to have the appropriate investment in probably not volume-driven reimbursements for these antibiotics or the value they bring to society and the peace of mind they bring to the family that if my kid gets an infection, my doctor has a whole set of drugs available to make sure we can succeed against that infection.

Meagan: And I was wondering if you could talk just a little bit more about the incentives that you think need to exist on the market in order to drive more innovation with antibiotics?

Martin: Yeah, yeah, as I said, right now, I think we have seen the results of not having adequate incentives in the system and why this therapeutic area for antibiotics has been really slowing down, while so many other therapeutic sales have had some breakthrough innovation in the past decades and so forth. When I step back, I think we need to look into the appropriate reward mechanisms, so I think there are different approaches that have been discussed. I think it has to be delinked from the actual volume and the actual use, because sometimes it's not appropriate to use the last reserve antibiotic more widely, etc. But the value to have that antibiotic that really strong one if everything else fails, etc., that peace of mind is real stumbling, and so I think rewarding companies who have put the risk into developing this, reimbursements that reward this, or that innovation for that peace of mind that they bring for the value to society that we can live normal lives and so forth, to be rewarding and therefore it's somewhat volume independent that people talked about subscription models, like a Netflix model, or perhaps how we pay for our fire station on the corner, right? Everybody pays a little bit, and not just the people whose house is on fire have to pay for the annual cost of the firemen and the fire engine and the building, and so forth. So, I think those are some concepts and I'm very pleased to see that there is even the U.S .Congress, some legislations that are being discussed that they're going in the right direction.

Meagan: Okay. So basically, you feel like there needs to be buy-in from the world's major governments?

Martin: Yeah. I think needs to start at the G7 or G20 and so forth, because we also need to make these solutions available to low- and middle-income countries at a price where they can afford it, right? At costs. And therefore, the solution has to come at a G7. We have what, a billion people from this thing of G7, a few dollars per citizen there can go a long way in reviving this.

Meagan: Now, you kind of touched on this at the start of our conversation when you were talking about just how bad the predictions are for the death toll associated with AMRs. Is there anything that you could add to this? What is sort of the worst-case scenario, you could envision if new antibiotics are not developed and brought to market?

Martin: Yeah, the worst-case scenario is what I described right at the beginning that we don't break the trend. And we discover too late that, "Oh, my gosh, what happened?" And it becomes more public. Right now it's a little bit, you know, who knew that 700,000 people die of bacterial infections and nobody talks about it? It's a slow creeping up crisis, rather than all of a sudden you have the crisis. So, that's my nightmares, and I hope and I'm hopeful that we won't get to this. From actually of all our entrepreneurs, I think we were a little bit of a catalyst for this discussion, the participants at our lounge meetings came as well from the political side, from the non-governmental organization, charitable organizations such as they're all set to writing. So. I think firstly awareness that something has to be done and the willingness to have constructive dialogue, I think is absolutely there.

So, that makes me hopeful that we can, we may not yet agree on what exactly is this, etc., we strongly believe and I strongly believe a market is the best provider of solutions. Therefore, let's make sure we have the right market incentives, and then I think the market will deliver the innovation that we need and the AMR Fund will be really supporting clinical development in this decade. But if we just do this and get two to four antibiotics, and then nothing else happens, that's not good. Those bugs continue to mutate, continue to grow resistance, etc. So, we have to find a sustainable model that drives that innovation. And again, for all the reasons I said, I'm cautiously optimistic that we will get there.

Meagan: Yeah. I was going to ask you how optimistic you are, you've kind of just answered this, but as someone kind of entrenched in this issue, and in the middle of it all and someone who's talking to various stakeholders in the value chain for this, are you feeling now like what needs to be done is going to be done by governments, regulatory agents, the pharma industry, health care professionals, etc., etc.?

Martin: I'm by nature optimistic, and I have a can-do attitude, etc. Of course, I was also talking to a lot of people who have been at it for decades and are a little bit burned out of this and cautioned me, etc. But I have to say, I'm really encouraged. And that's where, unfortunately, COVID-19, I think, is another catalyst that I believe helps change people's mind and saying, "Hey, we have to work together, we have to solve this because otherwise, we are on not a good trend." And it just causes too much human suffering, and potentially economic damage. Yeah, for really a serious reason here makes me more optimistic. And I think the industry is stepping up here, not from profit, interests, etc., but really they help solve a public health need. And with that, I hope we establish the basis for really constructive problem-solving dialogue. And I think you should put great minds together, and we come up with great solution. So, if the right intent is there, get the right people, I think we will solve that. It's absolutely solvable. So, that's my cautious optimism.

Meagan: After the industry, hopefully, we'll be able to claim victory over the pandemic, this will be the next major global health challenge that the industry can claim victory over as well. Was there anything really important to this discussion that we haven't talked about yet? Anything I missed?

Martin: Good question. I think you had some very, very good questions on that some that made me think as well, and so forth. I think we covered it all. I'm really humbled and honored to right now lead as the Interim, CEO of the fund. We are working feverishly, really at least six days, if not seven days a week on making this fund operational because we feel the sense of urgency. We expect to be operating by the end of the year, therefore, then looking into first investments in the first half of 2021. And so that's what now we're spending our energy on. We think the fund can do tremendous good for people, for the public health issue, but it won't solve it alone. We need to address it in a sustainable way; we need the collaboration of many stakeholders.

Meagan: Okay, great. Well, thank you so much for taking the time to explain this to me today. This was very interesting and informative, and it's such an important issue. So, I appreciate you taking the time.

Martin: Thank you very much for the invitation, it was a pleasure.

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