Presentations about Malaria at ExciPerience 2021
Malaria – one of the worlds most deadliest diseases!
Here you can see the keynote from Jennifer Cain Birkmose from www.mmv.org and our panel on malaria with Jennifer Cain Birkmose, Bahijja Raimi-Abraham and Sandra Klein at ExciPerience 2021 for free!
Keynote: Are public private development partnerships the future of R&D? How the partnership model for development in neglected diseases could be the answer!
Presentation from Jennifer Cain Birkmose at ExciPerience 2021
Beside the keynote, we also had the panel “Malaria and paediatric formulation needs” at ExciPerience:
Panel with Jennifer Cain Birkmose, Bahijja Raimi-Abraham and Sandra Klein at ExciPerience 2021
See the transcript of the panel “Malaria and paediatric formulation needs”:
Philippe: So first of all, thanks a lot for these great speeches that you just made. I think we touched all the topics on neglected diseases, malaria problematics, pediatric formulation development, fakes, so Bahijja just mentioned that one. But nevertheless, I would like to start with some questions because, as I mentioned at the beginning, there are some parallels in my opinion between pediatrics and malaria. For the pediatrics Sandra, the EMA has put up and the FDA, of course, has put up quite the program, the PIPs and the PUMAs of this world. So first question to you Sandra. Do you think this is enough for the future? Or how do you feel about this? And then I come to, of course, to Jennifer to ask the same question about malaria.
Sandra: I haven’t worked that much in malaria yet, but just wrote an application with some of my colleagues together. And what you see is that for big pharma there’s not a real market. So either they want to do something for the people there, but most of the big companies, they maybe offer their off patent tracks, and someone has to develop them. But for them the reimbursement for treatment is I think, half a dollar for two days treatment in malaria or so and so there is no real benefit. What you see is that there are off-patent drugs available, but if you want to develop them, it’s also quite tricky, Because we need to invest some money. And what happens is, so you need to write grant proposals, there is money there, but that doesn’t come from big pharma. And then later on, you need to connect with big pharma, again, to establish manufacturing processes, and then to transfer it into the countries where you want to treat people. I think it’s a lot of effort. And I think it’s mainly spin-offs, and then smaller, medium sized entities that try to develop pediatric formulation. But there’s always need for finding a sponsor for this.
Philippe: So you say that the major topic is here, in the end, the commercial value that they can do with pediatrics there. I think it’s just the reduced mass of patients that you can reach, right?
Sandra: I mean, in malaria you use many patients.
Philippe: Yeah, in malaria, it’s a lot of patients, but in standard pediatric cares, usually it’s neglected diseases or smaller populations.
Sandra: So there are only very few PUMAs. We are currently writing a paper with some people from, you know, PFI, and we had a look at how many PUMAs there are. And there are less than 10 PUMAs from the last almost 15 years.
Philippe: Wow.
Sandra: So you see hardly any. And then you see it’s too cost intensive. And mainly I know, the Alkindi product, for instance, was one. But most of this was funded by Horizon 2020 project. So a lot of money came from there, but not from pharmaceutical industry. When you go to industry and say, “Why don’t you use the PUMA incentive?” And they say, “Yes, we can do that, but it’s a lot of effort and costs, but there will be no refund for this.”
Philippe: So in fact, the whole PUMA and PIP approach is mainly to get through the adult formulation that goes on the market and it becomes hopefully a blockbuster. And it’s not really to bring good pediatric formulations on the market.
Sandra: And when you talk with some people, they are all interested in pediatric drug delivery, but I’m an academic, so I need some funding. And when you go to industry, there are companies that are very active. So I’ve also partnered with companies that are really active, that want to do the research. But there are many others that say, “Oh, we need a pediatric product, but we do not really want to develop it. So we hope that our adult product somehow works in pediatrics. And maybe we develop a smaller dose based on the formulation concept for adults and we are happy if this works. We don’t want to spend any time and money in developing a real pediatric product as such.” That’s a pity.
Philippe: Yeah, it is. So now coming over to Jennifer, Jennifer, how, apart from, you mentioned the sponsors, and you have a lot of private, very well known sponsors, of course, but how is the let’s say the support, the incentives from governments, really, regulatory environment that can help you to really go for something meaningful in malaria treatment, or let’s call it malaria and neglected diseases?
Jennifer: So we’ll talk about both. And Sandra, I think what you had to say inspired me to think about also other parts of the industry where one of my full time jobs is to be the head of patient access for a rare disease company where most of those rare diseases are targeted for pediatric indications. And so that’s something that we as a company are definitely looking at any type of incentive that does exist from a regulatory instrument perspective. And I’m inspired by, for example, right now, the European Council, the rotating European Council presidencies with Portugal, and one of the elements during this council presidency is looking at the pharma incentives, the orphan drug incentive, and specifically the pediatric orphan drug incentives. And of course, what we know, that’s all being opened up and being examined at the commission level, and making sure that we have the right incentives in place that encourage innovation, and open a pathway for innovation. And we’ll also, as a result confer sustainable access. Of course, when I’m speaking about all this, I’m speaking about this from a European perspective. I’m not speaking about this from a malaria perspective. I think those are two separate worlds.
So I think, from a rare disease, which is developing medicines for pediatric indications, specifically, there are instruments that are available that do enable pharma companies to invest in those areas to confer extended patent protection, which do allow for the investments to be recovered. Now, if we look at the malaria world, it’s a completely different course. And in my talk that I gave earlier today, we spoke about actually the role of patents, and the role of how patents are applied through the MMV model in the areas where malaria is endemic, and again, recalling that the most vulnerable populations that we are trying to develop medicines for are children under five, and pregnant women. And so I think, what’s just…I find fascinating about this model is that in those endemic populations, there is no patent protection. And so the model is such that they’ve been able to shape the regulatory environment to fit the regulatory…create the regulatory incentives for the model that they have to meet the public health need.
So it’s a very interesting model of creating…seeing the unmet need, developing for those populations, which are most vulnerable, bringing those products to market, and making sure that you have sustainable access, and making sure that the regulatory environments support that. So again, what we spoke of earlier is in the north and the west, in the globe, you do have patent protection over these products, because we’re trying to protect the supply, sustainable supply at endemic markets. So again, I think the whole reason that works and why does MMV still have that incentive, and in fact, pipeline in children for malaria is that you have sustainable funding, you have sustainable access. Like Sandra said, if companies don’t find that there is a incentive to develop, i.e. there’s a future market, they won’t. So again, MMV kind of takes some of that out, because you have the sustainable funding that’s there through these long term partnership contracts. I hope that helps Philippe.
Philippe: Absolutely. It’s where I was thinking in the direction. So it’s really the incentives for everybody to get something done. And I think you mentioned it in your talk, public-private collaborations might be one of the keys. Sticking to formulation, I would like to…this goes first for Sandra, talking about the different age groups, because we talk about pediatrics as one age group, which in fact, is at least five to six, depending on how you look at it. Right? And the challenges there I think one is of course, taste masking is always an issue with pediatrics, swallowability and stuff. But how do you cope with specific age differences in the formulation?
See also our article on the World Malaria Day
Sandra: I think the target is for sure to develop a dosage form that allows for flexibility, but it’s one individual kind of dosage form. So what we would propose here is maybe to go for a multiparticulate formulation because many of these products, when we talk about malaria, are fixed-dose products that we fix those combinations that we will see in the future or that are already there. So we have fixed-dose combinations of tracks that you can’t mix or that are, for instance, for that available as bi-layer tablets, because they are not stable. So there you have the opportunity if you have multiparticulates or even many tablets, that you can mix a certain amount or number and it can also adjust the doses with increasing age. I think these are viable approaches, because you have one formulation that you can vary with the different age groups. But then you need to be careful if this relates also to the question of how many multiparticulates can you administer? So the question is, when you have a very young child, so then you use a dose volume of a gram or so, you can’t do that. So it needs to be reasonable.
And it would always be nice that these are also all the experiments that we do, if you would have the chance, you have a solid dosage forms, but it doesn’t matter if you disperse it immediately before administration, so it would be nice to have a huge flexibility. And I always come back to the Alkindi because I like this product very much. We did a lot of tests where we simulated co-administration with common dosing vehicles in the European Union or also in the FDA environment, and we didn’t see an impact on track release. And this should be done also for the patients in malaria countries. And it would be nice if the common foods that they have, that are in use or prefer, if they would be compatible in dosage form. So this is a huge box where you have a lot of wishes that we should think about this. And as you hopefully could see for the liquid dosage forms, there is a lot of problems. But if you have a solid dosage forms, that you really could combine, where you also could combine two or even three models is because when talking about HIV, sometimes you need more than two doses, so similar problems. And this would be very nice.
Philippe: Thanks a lot. And Bahijja, a quick question to you on that. Also, drug delivery and reduction of side effects that we know with the normal malaria treatment there are, what do you see there as potentials that we grow into this area much better?
Bahijja: Yeah. I want to say thank you so much to Jennifer and Sandra for your honesty, because, often we don’t talk about the impact of…the financial impact of making medicines and the financial impact of even just having traction, and especially when you’re working and wanting to have impact for a condition, it doesn’t matter whether we’re talking about malaria, but any condition where, oh, can I say this, where it’s not maybe the popular one, where there’s a lot of support there. It is important to highlight that it is a challenge to even try and just investigate sometimes because we need money to do these things. So, I really appreciated the honesty from both Sandra and Jennifer on this topic, and how the whole different incentives, but the fact that we need more funding to be able to know more, and what to do. And so just to answer your question…I’m sorry, could you repeat your question for me? Sorry, I went off on my own tangent. Sorry. I just wanted to honor it, because I really just wanted to highlight that. Sorry, what was your question?
Philippe: Don’t you worry. This, I’m used by my wife. So, I ask a question and she goes off for something completely different.
Bahijja: You talked to me about side effects and impact.
Philippe: Yeah, exactly. I think a big topic is side effects and better drug delivery of antimalaria drugs as well. So do you have any insights there already? Or do you see…
Bahijja: Well, I guess, I always…well, not always. I often relate to my own experiences with medicines. And actually, my family heritage is Nigeria and Trinidad. And when I was younger, going to visit family in Nigeria, when we would arrive in Nigeria and you take whatever antimalarials, chloroquine, the nightmare of all things, sorry, but then it was always a thing of, oh, you had to take a quarter tablet, if you’re a certain age or half a tablet, things like that and the other. And those things, the fact that we don’t have enough, and Sandra and Jennifer touched on this, which is the need for accurate dosing and pediatric formulations specifically, this is…this will help to minimize the potential impact or potential for side effects or adverse effects because you’re getting the right dosing, if you have those flexible dosage forms. For pediatric formulations, people are still having to break a tablet in half, crush it, do all those different things, even just for taking the medication as well as also administering it. There’s so much risk, potential for risk and issues happening that way.
So I think that’s the context in which I see it, from a formulation and scientist perspective. How can we create and churn out better formulations for our target patient group, so that we don’t need to do things like break the tablet, if…you know, break the tablet, mix it…well, mixing can be fine, but I’m talking about breaking up the tablet, trying to find different alternatives. And then I think, taking into account the environments in which people are in, we’re assuming for certain malaria endemic countries, where we have to make sure we’re not seeing it from our own European lens, right? We need to make sure that we’re understanding access to medicine is not easy. Okay? So the effort and energy to go and get one dose or one course for whatever treatment, imagine if the person has to go back and get it. So are we making sure that those treatments are effective for that single use to cure? And I guess that should be the aim because you don’t know if the parent, if whoever, will have…be able to go back and forth to, whether it’s the…we’re assuming, again, the pharmacy. It could just be wherever they get their medicines from. You know, it’s legitimate…are we getting it from a legitimate pharmacy, source? Or is it somebody in the community who just happens to have access to whatever medicines that came off a truck and they say, “Oh, by the way, we’ve got these antimalarials or whatever.” Right?
And then there’s the other question of prophylaxis approach and treatment. We saw this a lot with COVID. If I can just talk about that briefly, where because of all this conversation about chloroquine, hydroxychloroquine, in countries where it’s easy to purchase those products, and other things that have come out potentially to have positive effects for COVID, people are buying them, taking them with no understanding of dose, with no understanding of strength, taking it, prophylaxis, because they’re scared. And you see that happen with other conditions, infectious diseases, as well. So yeah.
Philippe: Absolutely. And coming to Jennifer, you mentioned in your talk that we have increasing non-reaction on current medicines, so resistance, drug resistance. What do you see in the new drug development? So we mentioned with Sandra, and Bahijja, multiparticulates or adjustable dosing. So that’s the formulation topic. But do we also see new drugs on the horizon that cope with this, let’s say, resistance or multi-resistant activities?
Jennifer: Yeah. So very well spotted that we are in a race against time, every single day with malaria because we have resistance that is growing. And that resistance has to do with the natural progression and treating of this disease with the agents that we have. It also has a contributing factor from the substandard products that are circulating, and of course, the counterfeits, I know that we’re gonna touch on that in just a moment, but that there is a cost associated with those that’s more than financial, more than patient at risk, which is of course it’s patients at risk. And it’s putting the current supply of medicines that are out there, that are legitimately there to treat this disease…that can treat this disease, it makes them less effective because the agent becomes more…stronger, we’ll say, versus that which is already in the market. So yeah, I mean, it’s quite remarkable. Again, when you look at where we’ve come in the last 22 years, having 13 agents on the market that never would have existed because the pipeline was empty, we continue in phase three. We’re going into two…we’ve got two molecules that are entering into phase three. Now, there are nine that are either in exploratory, late exploratory into…entering into phase two or phase three.
So there are many new agents that are looking at…you know, of course, there are different formulations that are part of that development pipeline, but there are also new agents which look at, you know, more severe, severe forms of malaria, both mild forms of malaria. So we’re attacking the different…the different forms as well. But, I think the future is looking quite bright. There’s nine in translational phase as well. And then there’s another 10 that are actually in the target identification phase that might be going into human soon. So there are… I think the future looks bright. And I think… You know, anyone who’s working in drug development, you know that not every target, not every molecule that we’re studying is going to be successful. So the hit rate, we’re hoping to be very high, knowing that we may have failures because that’s part of drug development, but the future’s looking bright on what’s coming with the new formulations, which are accessible especially to the pediatric population.
Philippe: That said, thanks for that. And going a little bit away to another topic, but it has…this is, of course, an integral part of the whole discussion is the economical or economics. Sandra mentioned it for pediatrics in general. Both of you mentioned it before. And one of the topics that strikes me most is the matter of the fakes. And I just realized that my camera went off so I might not be transmitting anymore my picture.
See also our article on the World Malaria Day
Bahijja: We can see you.
Philippe: You can see me. That’s good. So… Stay flexible. As dosing for pediatrics, of course. Bahijja, you mentioned, the fake the fakes?
Bahijja: Fight the Fakes.
Philippe: Fight the Fakes activities, perhaps the ones that did not hear your talk, could you explain a little bit what you do there for the malaria? Before I go over to Jennifer to ask her about MMV.
Bahijja: Well, funny enough, the chair for the Fight the Fakes Alliances from MMV Adam Aspinall, so I’m in kindred spirits here. So Fight the Fakes… So I think it’s important to understand that the fake medicines world is actually quite a scary and dangerous place and… Sorry, I’m just gonna be honest, it is, it’s not a safe place, really. And it was nice to find an organization that are taking front and center in trying to address this issue, being a pillar for anybody who wants to be involved, anybody who wants to engage, anybody who wants to effect change in this area, you can do it with this organization as support. And so the Fight the Fake Alliance, as it’s now called, really aims to give a face and a voice to those who have been impacted by fake medicines. And I think, again, those things really resonate with me, which is a face and a voice, right? Because it can seem very impersonal, this whole issue of fake medicines. We’ve talked about it so many times today, in the last hour and a bit. But yeah, do we know if we’ve been impacted? Do we know people who’ve directly been impacted? And when you hear of people’s stories of how they’ve been impacted by this, it really makes you want to do something.
Now, the Fight the Fakes campaign initially was very much focused on advocacy and awareness. But it’s now moved more to what can we do to actually make a difference and have impact because I think there’s a time for advocacy and awareness, then there’s a time for action, and sometimes those move within each other. When I joined the Fight the Fakes Alliance and decided to set up the King’s College London Fight the Fakes chapter, it was because I was ready for action but I needed a little bit more understanding of the situation and the challenges. Yeah, I was like, I want to do it, but I don’t really know what I’m doing. Yeah, and so what we do with our chapter…and it’s a very important… So it’s linked a lot with my research as well. So I’m the founder and the academic lead, but I’m also an…I’m an academic so I look at the research aspects of things. And one of the things is I wanted to make sure we had a focus, not just because there’s so many…everything gets falsified, everything could be faked, and we focus on anti-infectives. And that’s partly because of the impact it has in antimalarials and malaria because of my research interests.
And that has also…have expanded a little bit just into general sort of infection and things like that. So what we do, we look at, again, as I mentioned, the advocacy and awareness, letting people know that this is a problem, but also bringing it, trying to tailor it to country-specific or region-specific as well. So whilst in, let’s say, in Europe, we have access to medicines via pharmacies and things like that, so you would think, oh, when you get your medication from a pharmacy, it’s not really gonna be falsified. But people purchase things online. People…you could go on, I don’t know if I can, but I’ve already mentioned you can go on Facebook, and then you might have been talking and Siri’s listening to you and then an advert will come up saying purchase this from here.
Philippe: Absolutely.
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Bahijja: Yeah, we just did a critical review on this. And we’re gonna publish this in the next couple of months, which is, what about the impact of online medicines, right? That impact…the access to medicines with online adverts come up on social media, and things like that so the fake medicine issue affects us all. And so yeah, I hope I’ve explained it. I guess, I’ve sort of given more of an advocacy pitch that told us what we really do.
Philippe: I mean, I can completely relate to that. I used to manage a bonded warehouse for medicines in Switzerland, and the customers would always show up at our end. And they said, “Look, you’re not an issue.” And we are going like, “But who’s the issue for fake medicines because we have about 30% of all the medicines in the world that are fake.” Said, “Look, it’s posted parcels, online shopping of medicine.” So that’s really an issue.
Bahijja: And if I could just quickly add to that, sorry, just to give a personal example. Amazon, because Amazon has now got the wholesale license, and there’s a big issue around people, patients…sometimes we have to remember that patients don’t have a healthcare or industry background. So if there’s a shortage from their local pharmacy, or wherever, and they say, “Ooh, where can I get it from? Oh, I’ll get it from Amazon.” They trust Amazon more than eBay because Amazon is portrayed as a reliable, reputable source.
I had a situation with a patient once in the community pharmacy, where he wanted to get…the person, sorry, wanted to get whatever medication. It was like over the counter thing. And I was like, “Oh, unfortunately, there’s still a manufacturing supply with that so there’s no access,” and then the person was like, “Oh, that’s all right actually. I ordered some off Amazon.” I was like, “I’m sorry, can you come back? Can we…can we talk about this please?” And I was like, “What do you mean?” And, basically, the person had ordered the muscle relaxants aspect of the medication from Amazon. And it was a dose that was double what’s in the over the counter medicine. So I was panicking. We talked it through, but he was like, “Yeah, but it’s Amazon. It’s reputable, right?” And I was like, mmm, you know? And so these are the challenges because people who sell on various different platforms, you don’t know how they’re storing their medicines, you don’t know where they’re sourcing it from. So these are things.
Philippe: Absolutely. We still got two minutes. And I have one burning question here. I have one burning question. We are not concerned until we are concerned. We had this with COVID. As long as it was over in China, we were not concerned. As long I don’t receive a fake medicine I’m not concerned. But we have a climate change coming. And this is…should not be a political statement. Sorry, for anybody that feels like. But Jennifer, how do you see the impact of climate change, malaria transmitting from the current countries to Europe, Northern America, where we’re not concerned yet, right?
Jennifer: Well, I mean, we’ve already seen that impact, even over the last four years with the growth of dengue, with the growth of…expansion of dengue, the expansion of Zika, for example. So these are things that will… You know, Europe, for example, was an endemic malaria zone, and even the Balkans, for example, in the Caucasus, we had malaria in these populations, until very recently. And so as we look at climate change, and as we look at temperate zones that are shifting, we already see the expansion of dengue and the like, and we will see malaria coming here. I like what you say it’s over there. It’s not over there because we are a global community. It’s here. It is in the human condition. And I think, to speak…there’s so much truth to, Bahijja, what she said about fakes and substandards. This is a serious issue. If we look at this from a global supply chain perspective for malaria, no matter where you live, right? And specifically in Africa, 60% of the malaria supply is currently seen as either substandard or as fake.
And I can trace back a few years ago when I had a wonderful course, actually, that I got to teach together with David Hill…David Holt, excuse me, from St. George’s University, maybe you’re working with him, Bahijja, in the U.K., where he’s actually doing a weekly, monthly tracking of substandards that are picked up and working with the procurement officers in Ghana, in Nigeria, also in East Africa. And these are individuals who do not understand the differences in substandard generic. So their fakes is a huge problem we know, which is linked to organized crime and has a huge economic cost and obviously a huge health cost. But the substandard generics, also a huge issue, which we…I think one of the things that we can all do as a community is keep educating governments, educating those who are procuring our medicines to ensure that we have safe regulatory instruments in place, safe testing as well, ensuring that we have the right level of active substance and safe excipients, Philippe.
Philippe: Absolutely. Thanks for the words. And with this, unfortunately, I have to close this session. It was great to have three such outstanding women that do great work in all their disciplines, bringing ahead these topics. It was lovely to have you with us. I hope you still hang around a little bit so that people that would like to get in touch with you have the opportunity. But of course, I also understand that if you have a lot to do because I know there is a lot to do out there and would really like to thank you. The rest of the attendees, it’s a break until we have our startup and innovation session for which we invited three startup companies bringing in some really…