This is our interview with Tommaso Prosdocimi from Iperboreal Pharma which was recorded for Solutions OP Clinical Trials podcast. You can listen to the original recording here. Please note that the interview below is adapted and not a transcript. This was done to improve readability.
Interviewer: Welcome to today’s episode of the podcast. Today we’re going to discuss dialysis solutions with a company based in Italy. But before I go into this one, I would like to say a few words why I decided to start inviting small companies and startups and discuss with them their work. So, we all know what the big companies think. We all know what Roche and Pfizer think and everyone else, but when it comes to the smaller companies, we don’t really know what kind of problems they have simply because their voices are not heard. I think we need to give a lot more opportunities to them to tell us about their problems and what they’re developing, because at the end of the day all big companies were once small companies, and they grew. We need to allow small companies who have new innovative products to reach the market and grow, and I think this is a very positive business attitude.
I would like to welcome today my guest who is the Clinical Operations Manager of Iperboreal Pharma, Tommaso Prosdocimi. As I mentioned at the beginning, Iperboreal Pharma is an Italian company which develops products for patients who are on dialysis, and today we’ll learn from him a bit more about what they’re doing, why their work is important, and also about the challenges they face. And I think finishing on a positive note, we can have some recommendations what we would like to see changed that could help companies like Iperboreal Pharma develop their products and reach patients quicker.
Thank you to Tommaso for joining me today and I’ll start with my very first question. Please tell me a little bit more about your company and what you’re currently working on.
Tommaso: First of all, thanks for having me on the podcast. We are actually not a traditional pharmaceutical company, where the products are discovered, developed, manufactured, and marketed. We are a super small team focused on Research and Development only. Iperboreal pharma is a scientific direction of a pharmaceutical company, a very little one, of course, without the rest of the operations. Our business model foresees to bring projects onwards as much as possible and reach a point where someone decides to invest in the idea we are developing.
So far, we were successful in bringing our main project to a phase 3 clinical trial. It’s called Elixir and attracted a collaboration of an international company, an Italian-based one, very famous, which is focused on home care services. They are called Divisor. We are now developing with them a food therapeutic platform to innovate peritoneal dialysis, both in terms of medicinal products and medical devices. The main idea is to overcome the main problems associated with marketed fluids, which is glucose-driven, local, and systemic toxicity. Without diving too much into the technical details, what happens locally on the peritoneal membrane is that glucose triggers some cellular processes, that build up fibrosis and make the membrane not able to act as an osmotic filter, sustaining the dialysis process and ultimately leading to a technical failure to continue peritoneal dialysis.
While on a systemic level, you should just think that we use a huge load of glucose that gets absorbed in the peritoneum. In pathology and stage kidney disease, where up to 40% of patients are diabetic, and where we know that there are cardiovascular complications, which are worsened by a bad glycaemic control, can significantly lower life expectancy.
We call our approach the osmometabolic one, as we want to substitute glucose with agents that are able to deliver a favourable effect other than only an osmotic capacity for dialysis. At the moment we have plenty of encouraging preclinical data. Some very interesting one to come soon in publication.
We have phase 2 study terminated with 12 patients treated and Elixir study is ongoing. If I remember correctly around 70 patients recruited so far and we aim to recruit 170 to terminate the study.
This is the main one, but we have also other projects.
For instance, one that I really love is that we think that peritoneal dialysis delivered with our approach may also be suitable for other pathologies that share fluid retention as a problem, and for which peritoneal dialysis is not indicated at the moment.
Above all, super interesting is refractory congestive heart failure, which is basically a condition of terminal heart failure where your heart does not work properly anymore. Kidneys are not perfused enough, and they lose performance, and a vicious cycle beats up. It is called cardiorenal syndrome. Basically, patients get severely congested, they can develop resistance to diuretics. And when this happens, they approach the end of life. Treating them with peritoneal dialysis is a way where their kidneys disposing fluids, will hopefully lead to regaining some function and restoring some sensitivity to diuretics as well. Of course, considering that we cannot cure them.
The main goal here is to improve their quality of life, which believe me is very miserable in these conditions. They are at a point where they are so congested, they can’t even breathe. They feel like they’re drowning. It’s terrible!
Methodologically speaking, it’s a very interesting project because here we are testing two interventions at the same time. Peritoneal ultrafiltration for failure and XyloCore, our investigational medicinal product as a peritoneal ultrafiltration solution, which is delivered to overcome those issues associated with currently marketed products. And that contributes to preventing peritoneal dialysis to be applied in patients with cardiovascular diseases.
This is a phase 2 study. It’s currently recruiting but, in this moment, we are working on a crucial amendment because we need to simplify the protocol and boost recruitment and also, we are looking for potential investors to join in the project because these studies are insanely expensive, and we cannot do the whole clinical development on our own, so we are still looking for someone interested in joining us.
We have some secondary projects too. Let’s say we have a super early drug discovery project that is focused on fibrosis-related pathologies. We submitted a patent in the late 2024. We have a great interest and published data on the potential to prevent or revert those several processes that are associated with the fibrosis. In this case everything starts from peritoneal dialysis where you have peritoneal fibrosis and it’s there where during our preclinical development we discovered this enzyme as a potential target for these pathologies.
We submitted application a couple of months ago to the pathfinder program in the European Union.
We are involved as partners in our new company that is going to be founded soon in collaboration with an institute in Milan, and we should be focusing on organ preservation and acute kidney injury prevention.
Interviewer: That’s brilliant. Thank you so much, Tommaso. It’s actually so interesting to see such a small company which does so much. If you think about it, big corporations have massive number of staff and when you’re a small company with several people, it’s extremely hard. It’s a lot of hard work for these companies and people like you to be able to do that.
I came across a couple of months ago there was a notification that FDA announced some shortages of dialysis solutions. How important is to have new dialysis products and more dialysis options for patients? Is there any global shortage or anything that you would like to share in that area?
Tommaso: I’m not aware of any current shortage, but I know there was one in the United States due to a problem on a plant which was very important for companies manufacturing and delivering peritoneal fluids.
You should consider that companies that deliver this kind of medicinal products are super limited, and this is the problem. So just think about that – in Western countries we basically have two of them. And I guess this has also impacted the opportunity for innovation in the field which is why it has been poor. Just consider that nephrologists basically have been using the same medicinal products for peritoneal dialysis for 20 years. The last revolution in our field was the introduction of Icodextrin as an osmotic agent, which was approved by FDA in 2002. So more than 20 years ago.
Of course, it’s extremely important to provide patients with as many renal repairs replacement therapies as possible and let them decide with their physician, which is the best therapy for their specific case. The peritoneal dialysis is one of the options they had historically, and it was considered as a second choice.
There are many reasons for that, for instance, in the early decades of dialysis, peritonitis rates were extremely high and could be life threatening. Because access to sterile supplies and good technique was limited haemodialysis at those times seemed safer. Haemodialysis allows a rapid removal of fluids over a few hours while peritoneal dialysis relies on a slower and continuous exchange, we can be less precise and unstable, but actually we know now that this is an advantage because you preserve the function and you slowly dialyse the patients and it’s more biocompatible. Then also nephrologist and dialysis nurses historically were better trained and equipped to deliver haemodialysis. Hospitals had more haemodialysis infrastructures, and this led basically to a sort of hospital-based culture following haemodialysis rather than peritoneal dialysis.
Then you have other historical issues like peritoneal membrane tends to lose its transportation properties over time and this happens because of glucose, and this is exactly what we are trying to address with our product. There are other reasons, but the news is that disadvantages of peritoneal dialysis are not true anymore. So it’s getting more evident that peritoneal dialysis carries significant advantages over haemodialysis. First of all, it’s not a hospital-based therapy which provides the possibility for a more independent life to patients. For example, if the patient does not live close to a dialysis unit, this is an important problem. It also allows for a better preservation of residual kidney function, as I mentioned before, which we know is a key important factor for long-term outcomes. It is also more cost efficient.
So, keeping in mind this, we are probably going to see an increase in peritoneal dialysis usage over the next years. And for this reason, we have to elevate its standards and provide better medicines and medical devices as well. One of the challenges is glucose, and this is where we are trying to do our work.
Interviewer: That’s brilliant. Basically, if you have so few companies actually working in that field, it’s risky potentially for the patients because if, for whatever reason, someone is not able to manufacture something that could potentially lead to drug shortages. And this could be really critical for the patients but also for the science because few companies doing the same stuff it’s not really pushing things forward.
Tommaso: Competition is pretty important for this. If you don’t have competition, you don’t have the momentum you need for research.
Interviewer: Yeah, I absolutely agree with you on this one. That’s really a brilliant point. I’ll go to our very last question, which is quite a big one. My very last question is about the challenges that you face as a company developing dialysis products for patients and also what is on your wish list, what you would like the regulators to change that could potentially help companies like yours.
Tommaso: First of all, let me say that I really hope to not analyse this topic too much because I might be a little bit too young and not so experienced to see what the real issues are in our system, but I think that our regulatory framework has become insanely complex. And with complexity comes costs and costs are not affordable for everyone, especially for smaller companies.
I have some examples for you where I really struggle to push my project forward.
First of all, we distribute our investigation medicinal products directly to patients. However, the regulation obliged me to include on the labelling what is called “variable information”. This is like site code, patient code, investigator’s name and so on. But if I do something on the packaging, such as adding labels, I have to do it in a GMP environment, in the GMP facility, and release the product afterwards. Basically, the regulatory framework is forcing me to hire many GMP facilities for international studies and releasing the product every time I make a shipment to a different patient. Now we mentioned our case in which we have 85 patients, which is not a huge number for clinical trial. They must be supplied monthly for 6 months. It means we have to process and release in a GMP facility 510 blocks of investigational medicinal product. This is a huge cost. I can say that’s maybe around 50 million Euro just to write something on a label. Patients are not more protected. The quality of IMP does not change. It’s very expensive bureaucracy. This is where we could just release the product after the manufacturing and just do labelling in a normal facility. This is what hospital pharmacies do in their practice because hospital pharmacies are not GMP units. So, this is already being done at the hospitals, but you cannot do it as a private company, and this is generating the mess. I think it’s completely crazy.
Interviewer: That’s very incredible.
Tommaso: If I think the amount of money we are using just for this is completely crazy. We could have done another study just with the money we are losing for distribution.
Another example is the number of authorities and ethic committees that have to approve a study. So, things are getting better with EU regulation 2014. Finally, at least we have a single ethics approval in Italy, consider that, until a couple of years ago, we had basically as many ethics committees as many hospitals you were including in the study. But this is not enough because for interventional clinical trials at the moment, which are managed by CTIS, we have to seek approval from the reference member states, so a part 1 goes to their competent authority and a part 2 is for their ethics committee. Plus, all other committees for each country that is included, plus a revision for every competent authority for any country included. So, what’s the point here? I think we are saying that the study may be ethical in one European country and not in another, but I don’t think that is so. Or are we saying that we trust a reference member state to evaluate part 1, but not completely, so we want other competent authorities to acknowledge their decision? Why? So, of course this in my very humble opinion, generate complexity and cost. And again, the very big problem is that costs are not affordable for everyone.
Then we have another very classical case, it’s GDPR, the data protection law. I think we may really open an infinite debate on this topic, but I guess most people working in clinical research notice that GDPR is insane when applied to the world.
Just an example, everyone knows that the sponsor basically can use patients’ data and, I mean anonymised clinical data, not identifiable data, for the purpose of a certain study only. But why? Just think how much additional research we could do if that could be processed in other ways too. Because once I collect the data it would be reasonable to use it as much as possible. For instance, someone generating data may share it, for the purpose of other studies, to other companies, to other research institutions with the first aim of delivering benefits to research and ultimately the society, but you cannot do this.
On this matter, I think there is a lot of heterogeneity in Europe in the way the studies are evaluated. In the past, it happened to me that one ethics committee invalidated the approval of another ethics committee on a collection of samples for future studies. And what is really interesting is that they didn’t provide a formal justification. They just said that the ethics committee does not like it and I’m basically citing what they said: “This ethics committee does not approve this approach.”. And it doesn’t matter that the project was previously approved by another committee.
We need more clarity on what we can do, and we should be more flexible using data for the sake of research.
Then you have negotiation with the hospitals. This is very well-known issue. Why do we have to deal separately with any hospital, even when they are public hospitals? Why we have to negotiate the price with anyone? Why we can’t have a sort of algorithm to define the patient fee and study specific costs once for the study.
This is another process that it’s taking many, many hours of work, much money spent, much time lost, when everything may be efficiently managed by a website, generating patient fees and negotiating a single contract at least on a national level.
But I know that in the UK it’s slightly better than in other countries in Europe, but my experience with the UK is that at the end of the day you still have to negotiate the contract with the specific hospital administration, so you solve this problem partially.
Interviewer: Well, and that’s a very good point, but the problem with negotiating with different hospitals in the UK is because they have extremely bureaucratic internal procedures. So just to get a study set up, they need to get approval from this department and that department and everything takes a long time, even for a simple observational study sometimes they need to go through some committees and stuff where you think “Well, it’s just observational study.”
Tommaso: Why do you need this?
Interviewer: I think it’s internally created bureaucracy. Otherwise, the mechanism is very much what you described in the UK. We have a standardised cost, and we have standardised contract. But on the hospital level this is where things slow down and become very long and tedious, but I guess in many cases you are basically working more but you’re not really adding value to the process, and I completely agree with you.
I think the requirement to have GMP facility to do labelling, something which is not critical. It’s like a very simple label to put. I think they have really overdone it. I don’t know who came up with this thing, but they’ve definitely overdone it.
The problem is that many regulators, because their feedback is mainly from bigger companies, they don’t really understand that this is a massive cost for a smaller company, and it could prevent them from running more studies and developing new products simply because they’re paying for labels.
Tommaso: But the most interesting example that I have for you is about IMP. As I mentioned before, we have this study where we deliver the IMP directly to patients. It was set up as a study before – under directive 2001 – which is the European directive before the 2014 regulation and before the guidelines for decentralised trials were published.
In Italy we have a law which forces investigation medicinal products to be delivered directly to hospital pharmacies only. So, it presented to us the problem on how to deliver tons of litters of dialysis fluids to hospital pharmacists that are not used to this. Peritoneal dialysis fluids are normally supplied directly to patients’ home as part of the clinical practice. Consider that a patient treated with the full dose of manual version of peritoneal dialysis uses 8 Liters of product per day. A patient which uses the automatic version may reach 15 Liters per day.
This is impossible! At the time, I was managing the study I was working for the CRO and we did not know how to overcome this problem, so I decided to start discussing it with those directly interested which are hospital pharmacists and, believe me, it was insane. I had several surreal conversations where the pharmacists agreed with me that it was not possible to deliver these kind of products directly to them. At the same time, they were clarifying that even if it was possible they cannot organise a shipment to patients. And also they clarified for me that they were not in the position, and they had no right to authorise us to do anything other than giving them the product, which was not possible. Basically, we found ourselves at a point where the study was not feasible. Not for the design of the study, but because of logistics.
The funny thing among these conversations was that I also had a discussion with an administrative person in a certain hospital where they suggested the principal investigator to personally deliver with his own car fluids to patients. Wonderful!
At the end of the day, we took the only way out we saw, and we asked the competent authority.
Eventually, we were authorised to bypass hospital pharmacies based on many quality standards to be respected such as adding a dedicated portal accessible by pharmacists for product management and GDPR constraints and so on. And we developed the system with our providers. It was a nice journey. Everything took place before the publication of the decentralised guidelines.
I would like to think we were one of the first, at least small companies, trying to do something similar with that research framework that was clearly against us.
So, my final point is that the research is universally considered a good thing. I think everyone can agree with this. If the clinical research framework works properly, you attract investments. Your patients have anticipated access to new therapies and hopefully products are also marketed firstly where they were developed and that leads to other patients have access to the therapy too. Commercial research is well paid, and the healthcare system can spare money. Just think of all these drugs sourced and provided for free as well as all those fees and examinations paid with in-patient fees.
This is clearly a win-win situation for companies and institutions that must be pursued as much as possible.
On the contrary, if the research framework is too complex; it’s too bureaucratic; too expensive; too slow, you are losing the opportunity, and this is an advantage for other countries where maybe regulatory frameworks are easier.
I really think we have to make research doable in the easiest way possible. And it must be affordable.
Of course, we have to prioritise patients’ rights and safety, but I really don’t think this comes with bureaucracy. That’s the main point.
Interviewer: I completely agree with you, and it’s quite fascinating to learn about these completely unnecessary challenges that companies like yours, which is developing new dialysis solutions, are facing because of logistical issues or some contradictions in the law or because you’re required to have GMP facility for labelling for something that pharmacies could normally do themselves.
It’s quite it crazy situation, but that explains why not many companies are doing that kind of work if we create challenges on every step for them and if we make it extremely expensive, obviously they cannot afford it and that’s why they don’t develop new products and then at some point we sit and think “What happened? Why don’t we have any more dialysis solutions? Why is no one working in this field?”
And I think now we have a very clear answer to this question.
Thank you so much, Tommaso, for joining me today.
