Speaker 1: Hi, I'm Aaron Welsh and this is this podcast will
Speaker 1: Kill You. Welcome back. You are listening to another bonus episode,
Speaker 1: our second in our mini series of bonus content, exploring
Speaker 1: in more depth the topics we covered the previous week.
Speaker 1: As we always say on the podcast, A we're not experts,
Speaker 1: and B we can't cover absolutely everything about a disease
Speaker 1: or a topic in our regular episodes, and those two
Speaker 1: things probably aren't going to change. But we can talk
Speaker 1: to actual experts in the subject we covered the previous
Speaker 1: week and get to explore some aspects of that topic
Speaker 1: in more detail than we did in our regular season episode.
Speaker 1: In our first bonus episode, I followed up our hepatitis
Speaker 1: B episode with a conversation with doctor Sherry Cohen about
Speaker 1: the stigma and discrimination that people living with hepatitis B
Speaker 1: often face and how it impacts their lives. This week,
Speaker 1: I'm very excited to chat with doctor Wilfried Matombolkoloji and
Speaker 1: doctor Natalie Stroborgaft from the Drugs for Neglected Diseases initiative
Speaker 1: about Human African tripanisamiasis. In particular, I wanted to learn
Speaker 1: more about the development of fecsinidzol, a new drug to
Speaker 1: treat this disease, one that is much safer and easier
Speaker 1: to use than those that have been historically available. How
Speaker 1: is this drug discovered, what are some of the challenges
Speaker 1: in making sure people who need it have access to it?
Speaker 1: And what impact has it had on control efforts? These
Speaker 1: are just some of the questions I want to explore
Speaker 1: in this bonus episode. If you haven't listened to our
Speaker 1: Human African tripanasimiasis episode yet, you may want to do
Speaker 1: so before you listen to this bonus episode because there's
Speaker 1: just so much to that story and it'll probably help
Speaker 1: give a bit of context for this interview. But either way,
Speaker 1: I'll give a quick overview before we begin. Human African tripanasimiasis,
Speaker 1: also known as hat hat or sleeping sickness, is a
Speaker 1: neglected tropical disease caused by two subspecies of tripanosome parasites,
Speaker 1: one of which Tripanosoma brucei gambience, is much more common
Speaker 1: than the other, Tripanosoma brucei rdisience. These parasites, which are
Speaker 1: transmitted through the bite of a setzifly, have been infecting
Speaker 1: humans for thousands of years and cause a disease that
Speaker 1: is considered fatal without treatment. Over the past fifty years
Speaker 1: or so, there have been substantial global and national efforts
Speaker 1: to reduce the prevalence of human African tripanisimiasis, and we've
Speaker 1: made a great deal of progress towards elimination. For instance,
Speaker 1: from two thousand and nine to twenty twenty, the number
Speaker 1: of recorded cases dropped from just under ten thousand to
Speaker 1: six hundred and sixty three, which is absolutely amazing. But
Speaker 1: still these parasites persist in thirty six countries in Sub
Speaker 1: Saharan Africa, with some countries carrying a disproportionate burden of disease,
Speaker 1: such as the Democratic Republic of Congo, where seventy percent
Speaker 1: of cases reported over the past ten years have occurred.
Speaker 1: Control and elimination efforts for human African tripanisimiasis face many
Speaker 1: different challenges. For instance, these vector borne parasites have a
Speaker 1: supercomplex eco pology, Diagnosis of the disease can be quite tricky,
Speaker 1: and there are many logistical difficulties in providing care to
Speaker 1: those who need it. Funding for research or drug discovery
Speaker 1: is always a challenge, and for decades the only available
Speaker 1: treatments were either arsenic based with toxic side effects. These
Speaker 1: drugs are called arsibol or malarsaprol or extremely complicated to administer.
Speaker 1: These last points have changed in the past few years
Speaker 1: with the discovery and approval of fecsinitisol, which is an
Speaker 1: oral treatment effective for both the first and second stages
Speaker 1: of gambience human African tripanisimiasis. This drug was developed through
Speaker 1: a collaboration between the French healthcare company Santo FI and
Speaker 1: the Drugs of Neglected Diseases Initiative. And I am super
Speaker 1: thrilled that I get to speak with not one, but
Speaker 1: two amazing scientists at DNDI about this exciting new development
Speaker 1: and what it means for the global elimination of human
Speaker 1: eye African tapanis miasis. Doctor Motombo Colomgi and doctor Stuboorgaft
Speaker 1: have both been involved in many different aspects of human
Speaker 1: African tapanistas's control efforts, from regional fieldwork to clinical trials,
Speaker 1: and from drug research and development to forming industrial partnerships
Speaker 1: to bring these drugs from the lab to where they
Speaker 1: are most needed. And I will let them tell you
Speaker 1: a bit more about themselves and jump into the interview
Speaker 1: right after we take this short break.
Speaker 2: I'm Wilfrid m I'm a medical doctor. I'm based in
Speaker 2: DRC in Democratic Republic of Hongo in Kinshasa, and I'm
Speaker 2: working for the NDI currently, I am coordinating our local
Speaker 2: R and D T and we're working up current you
Speaker 2: on three diseases, Scenario, disease and COVID, so I'm coordinating
Speaker 2: all our R and D projects.
Speaker 3: My name is Natalie football Geft. I'm a medical doctor
Speaker 3: by training. I've been with d NDI since two thousand
Speaker 3: and nine and I've been leading the NTD, R and
Speaker 3: D activities and started the vaccini as our program in
Speaker 3: two thousand and nine until it came to access to
Speaker 3: patients in two thousand and eating.
Speaker 1: Thank you so much for taking the time to chat
Speaker 1: about d NDI and vaccinate as all. So I wonder
Speaker 1: if you could start off by telling me how did
Speaker 1: you both get involved with DNDI. What brought you to
Speaker 1: this type of work.
Speaker 2: My first term to hear from the NDA was in
Speaker 2: two thousand and six. I was working as a doctor
Speaker 2: in a remote village, so I heard that the NDA
Speaker 2: was preparing the project of clinical trial on art human Africans.
Speaker 2: So I was interested because I was treating those passions
Speaker 2: and so I was aware of issue we had with
Speaker 2: this disease, and then I applied and I was selected
Speaker 2: to be a local PI principal investigator for one of
Speaker 2: clinical side study, so it since two thousand and six.
Speaker 4: That was my first.
Speaker 2: Contact, and then after I continue, I was investigator in
Speaker 2: another clinical trial that was called Nightfield, and then after
Speaker 2: from two thousand and twelve, I start working as coordinating
Speaker 2: and a skepter of affecting as all projects and seis
Speaker 2: two and sixteen full staff of the NDA.
Speaker 3: As for me, it's a bit different. I've been working
Speaker 3: before in the pharmaceutical industry and in some biotechs, and
Speaker 3: in fact, in two thousand and three, when DNDI was launched,
Speaker 3: I was informed via friends and I kept watching the
Speaker 3: DNDI website for interest because I've always been interested in
Speaker 3: doing something that adds value to public health. And once
Speaker 3: I saw a position that was opened for clinical development
Speaker 3: director and I called them and I said, this is me,
Speaker 3: this is me, and they were at the end of
Speaker 3: the process, so they accepted to receive my CV. I
Speaker 3: went through interviews and I got the position, and that's
Speaker 3: how I came with d NDI, and I'm still.
Speaker 1: There wonderful so today will mostly be chatting about human
Speaker 1: African tripanasamiasis, but DNDI is involved in control efforts for
Speaker 1: many other neglected diseases. So can you talk briefly about
Speaker 1: the general missions of DNDI and what type of work
Speaker 1: the initiative does so you know, in.
Speaker 3: Fact, yes, the NDI was founded in two thousand and
Speaker 3: three after MSF Doctors Without Borders received their peace Nobel price,
Speaker 3: and some people at MSF, in fact, doctors who were
Speaker 3: working in the field, were facing terrible dilemma where they
Speaker 3: couldn't treat patients who they were trying to take care
Speaker 3: of because they didn't have the proper tools, the proper treatments,
Speaker 3: and so they started looking a little bit more and
Speaker 3: it was very clear that there were a range of
Speaker 3: patients or diseases that were totally neglected by the efforts
Speaker 3: of the industry because they were targeting diseases and all
Speaker 3: populations that had no economic power and for which there
Speaker 3: would never be what was expected to be needed, i e.
Speaker 3: Return of investment. So they developed the model, and at
Speaker 3: that time there were a few others that started developing
Speaker 3: what was called product development partnerships, looking at ways of
Speaker 3: developing treatment options that would be responding to the needs
Speaker 3: of those that are neglected by this industry, and that's
Speaker 3: how the NDI decided to focus initially on developing a
Speaker 3: combination of foral treatment for malaria fixed those combinations that
Speaker 3: was aligned with what the WHO was asking for at
Speaker 3: that time, but also focus on some specific diseases where
Speaker 3: there was both a need some partners and a hope
Speaker 3: for short, medium and long term response. And that's how
Speaker 3: a few diseases were selected from the list of neglected
Speaker 3: tropical diseases, which included mostly kinitoclastic related diseases so parasitic
Speaker 3: diseases including sleeping sickness, jagas and lehmanniasis. And then we
Speaker 3: expended every three four years we had a revision of
Speaker 3: the strategic plan and based on needs and opportunities, we
Speaker 3: expanded to encore psarkiasis, to pediatric HIV, which might come
Speaker 3: as a surprise but very neglected in sub Saharan Africa,
Speaker 3: and also hepatitis C and then mycetoma also extremely neglected.
Speaker 3: And then in twenty twenty we started, as wolf Kind mentioned,
Speaker 3: to engage in two COVID response, but COVID response for
Speaker 3: low and middle income countries.
Speaker 1: The global efforts towards elimination of human African trim panicema,
Speaker 1: they've been amazingly successful over the past ten years. For instance,
Speaker 1: I saw that only six hundred and sixty three cases
Speaker 1: were reported in twenty twenty, which is a drop of
Speaker 1: over three hundred from the year before. That's an incredible
Speaker 1: drop in cases and it shows that real progress is
Speaker 1: being made. What do you think are the biggest factors
Speaker 1: contributing to this decline in human African tripeness and ISS cases.
Speaker 2: It was the dagnostic that was very, very difficult, and
Speaker 2: the second and very big challenge was the treatment.
Speaker 4: Because the treatment we used to lose was.
Speaker 2: Archobal with arsenic and that treatment was toxic and less effective,
Speaker 2: was losing its effectiveness. And I think the great moment
Speaker 2: was when the NDA was involved with all his partner
Speaker 2: and when we change the treatment. The first wed step
Speaker 2: was to change to switch from the arsable to net
Speaker 2: the combination of thirty knox and this was the first.
Speaker 4: Quick step we did.
Speaker 2: But this changing of treatment, we had a very effective
Speaker 2: drug and less toxic and so we we have very
Speaker 2: very few relapse and even people was very comfortable to
Speaker 2: receive this treatment. This was I think for me, the
Speaker 2: very critical moment, and with our involvement of d n
Speaker 2: D and this partner, we are still working on the
Speaker 2: best way to ease the treatment and now we are
Speaker 2: on oral treatment.
Speaker 4: So all this was very important and very critical step
Speaker 4: toward the elimination.
Speaker 3: Yeah, so maybe I think we should also recognize the
Speaker 3: from the I mean, this is what Wilfred mentioned, but
Speaker 3: under the umbrella of national sleeping Sickness control programs and
Speaker 3: collaboration with many partners, which I think under you know,
Speaker 3: they're also the leadership of the who all of this,
Speaker 3: there was a momentum and a push to consolidate to
Speaker 3: have joined efforts on diagnostic and treatment. A lot of
Speaker 3: training activities performed via the national programs, and since Wilfred
Speaker 3: was also part of the national programs, maybe that's why
Speaker 3: he's being modest, But I think we should recognize that
Speaker 3: the organization at the country level was was also absolutely
Speaker 3: crucial in making this reality.
Speaker 1: So you have both been working in this field for
Speaker 1: a number of years and have had this opportunity to
Speaker 1: witness this drap in cases firsthand. So how do you
Speaker 1: feel that this field has changed since you first became involved.
Speaker 2: I did my medical training in the side province, so
Speaker 2: this was one of anemic areas of sleeping sickness. So
Speaker 2: even during my training, I was seeing how those passions
Speaker 2: was treat with melasoprol. And when I became a medical doctor,
Speaker 2: I was in charge of managing those persions in my
Speaker 2: small village where I was working, and you know, I
Speaker 2: was receiving those passions and the only drug we had
Speaker 2: at that time was melasoprol. This was terrible drug. I
Speaker 2: even lose lost two of my patients. It was a sad,
Speaker 2: very bad experience. You know, when we were treating passion
Speaker 2: with a SOB, it was stressful not only for health worker,
Speaker 2: but you.
Speaker 4: Know even for passion family. So but since we have
Speaker 4: those new drug.
Speaker 2: Things change, you know, we have even health worker are
Speaker 2: more comfortable, more confident.
Speaker 3: This is a which change and I think the key
Speaker 3: point is also that people are less less afraid of
Speaker 3: going for treatment. But maybe also with time they will
Speaker 3: also be less stigmatized because you know, less mystery is
Speaker 3: surrounding this disease. They can with with vacciny asert patients
Speaker 3: can be treated in the village. There's nothing magic about
Speaker 3: you know, the treatment patients come and some of our
Speaker 3: colleagues used to say the success will be one day
Speaker 3: when you consider sleeping sickness as any other infection, it
Speaker 3: has been, you know, impacted by a lot of stigma.
Speaker 3: That this stigma I think may decrease with getting a
Speaker 3: treatment that looks like any other treatments. It's tablets, there's nothing,
Speaker 3: no specific requirements regarding you know, its use, protection of
Speaker 3: activities you shouldn't be doing when you take the dragon,
Speaker 3: a lot of things which make it really more normal,
Speaker 3: and that's really important because what we need is patients
Speaker 3: to be treated. What we have observed is that patients
Speaker 3: have come, sometimes come very late for treatment because treatment
Speaker 3: before meant going to hospital, which meant not being able
Speaker 3: to work, which meant maybe having an economic impact on
Speaker 3: the family, which meant also that the family had to
Speaker 3: accompany patients at the hospital pay for fees. I mean
Speaker 3: a lot of things which are impacting the quality of
Speaker 3: life and the acceptability of treatment. So it's a huge change.
Speaker 1: One of the things that I wanted to ask about
Speaker 1: was the COVID nineteen pandemic. How has this had an
Speaker 1: impact on control efforts? Do you think that we'll see
Speaker 1: another decline and reported cases of human African tripanismiasis from
Speaker 1: twenty twenty one or has the pandemic impacted control efforts?
Speaker 2: So sure, yes, the pandemic is an impact on control efforts.
Speaker 2: You know, most of the National program works with what
Speaker 2: we call mobile team, and those mobile teams walk twelve months.
Speaker 2: Every twelve month, they spend more than twenty days or
Speaker 2: more than fifteen days going from a village to another
Speaker 2: doing the screening of population. So it's not easy for
Speaker 2: them to go from a village to another village due
Speaker 2: to COVID restuction, and since we have this COVID problem,
Speaker 2: you know, they are not able to have a twelve
Speaker 2: months of work. This is another problem. And you know
Speaker 2: we work with many partner, many founding partner with COVID.
Speaker 2: Their impact to SAW the National program you know, receive
Speaker 2: not the entire money for their activities. So this is
Speaker 2: a second impact and another impact. You know, if we go,
Speaker 2: for instance, in the field of another elective disease like
Speaker 2: filarial disease, they do what we call mass rog administration.
Speaker 4: They can do it.
Speaker 2: You know, last week I was leiting some remote areas
Speaker 2: and then the mass rog adminisation was not done.
Speaker 4: Due to this COVID issue, due to this restriction of
Speaker 4: movement and due to.
Speaker 2: The decrease of finance. So this COVID will have a
Speaker 2: good impact and we must be aware of this.
Speaker 1: I was wondering if you could talk a little bit
Speaker 1: more about the stigma surrounding human African tripanosamiasis.
Speaker 2: Yes, as you know this it's a chronic disease. The
Speaker 2: first step is what we call a molempathic step. The
Speaker 2: second stage, it's neurological stage. And at that stage, you know,
Speaker 2: can become like a foolish you know, mostly pe and
Speaker 2: so on, with a trouble of theev and so on.
Speaker 2: And for those who suffer from sleeping sickness, this was
Speaker 2: a very with sigma. That was one of the factors
Speaker 2: that could avoid some people to come to receive the treatment.
Speaker 2: But now sleeping sickness are more and more accept and
Speaker 2: are being humanized, you know, now things are changing.
Speaker 1: In our episode on human African tripanos semiasis, we touched
Speaker 1: briefly on vacting it as All, which is this oral
Speaker 1: medication recently developed to treat this disease. Can you tell
Speaker 1: us a bit more about the drug, starting with how
Speaker 1: exactly it works.
Speaker 3: We haven't fully elucidated the mechanism of action of vacciny desert,
Speaker 3: but we know it interacts with the enzi material of
Speaker 3: the parasite that is responsible for the disease, so it
Speaker 3: is innocence, it kills it.
Speaker 1: How effective is it for gambiensa?
Speaker 3: So it's really effective. So we did a study, a
Speaker 3: very robust study in comparison with the NEXT, which is
Speaker 3: the standard of care mentioned earlier by we FEED, and
Speaker 3: we showed that it was non inferior to it, which
Speaker 3: was the statistical hypothesis, within a limit of thirteen percent,
Speaker 3: which means that in essence, it is almost as equivalent
Speaker 3: as NEXT, with slightly lower efficacy, but within a range
Speaker 3: that is considered as really what the physicians wanted and
Speaker 3: what the regulators accept. So it's very important because it
Speaker 3: means that with an aal treatment you can replace an
Speaker 3: injectible treatment and something else, a combination of an injectible
Speaker 3: and oral treatment. But I think something we haven't yet
Speaker 3: mentioned is that to administer the standard of care, which
Speaker 3: is NEXT, you need to have patients being hospitalized, but
Speaker 3: before that they need to go through a lumber puncture
Speaker 3: to verify if they are eligible to this complex but
Speaker 3: very effective treatment combining an infusion and a normal treatment,
Speaker 3: or if they can stay with an intramuscular treatment, which
Speaker 3: is simpler to use, but still to get this standard
Speaker 3: of care, they need this lumber puncture. The lumber punctures
Speaker 3: are painful. Some of us who have had lumber punctures
Speaker 3: in the past, we have access to anastasia, but that's
Speaker 3: not the case when you do lumber puncture to test
Speaker 3: patients for treatment allocation. You have headaches first lumber puncture,
Speaker 3: and that's also one of the factors that made sometimes
Speaker 3: patients want to avoid being tested just for the sake
Speaker 3: of not having to go through this lumber puncture. Now,
Speaker 3: with vaccin need as a you don't systematically need a
Speaker 3: lumber puncture. You may need it if patients are experiencing
Speaker 3: severe neurological symptoms, where maybe they would benefit more from
Speaker 3: this standard of care treatment, but otherwise, once a patient
Speaker 3: has been tested with the parasite, that patient, provided he
Speaker 3: doesn't have very severe symptoms, can get oral treatment immediately.
Speaker 3: It has also shown us that it has really high
Speaker 3: efficacy in stage one, meaning that those patients were not severe,
Speaker 3: and it's also as efficicious in children, which is very
Speaker 3: important as well, because otherwise those small kids would require
Speaker 3: the lumber puncture if they are in the advanced stage,
Speaker 3: and would require the infusion, the combination of infusions and
Speaker 3: oral treatment. So overall it is almost the same as
Speaker 3: the standard of care, but it's oral and doesn't need
Speaker 3: the lumber puncture.
Speaker 1: That's wonderful. Yeah, And I'd love to hear more about
Speaker 1: the story of the drugs discovery. How is it selected
Speaker 1: as a potential candidate for a sleeping sickness medication and
Speaker 1: then what happened after that?
Speaker 3: So that came from the well, the way we worked
Speaker 3: at the NDI, and it was our predecessor, so elsto
Speaker 3: Rele and bernardet Bourdain who evaluated drugs of the class
Speaker 3: nitro medesol class because they were known to have a
Speaker 3: potential for this disease, and looked at a library or
Speaker 3: I think of almost seven hundred drugs and started looking
Speaker 3: at the potential for those drugs. Vaccini Desol came out.
Speaker 3: It had been developed earlier on by predecessor of Sanufi
Speaker 3: and put on shelves before it came to clinical stage,
Speaker 3: just for probably you know, strategic reasons. Nothing else so
Speaker 3: it was identified back from the shelves and then as
Speaker 3: the value chain of clinical development evolved, meaning looking at
Speaker 3: individro testing on parasite labs, going to animals to test
Speaker 3: the efficacy of the drug in animals infected by the parasites.
Speaker 3: We selected the end vacciny as a clinical candidate, at
Speaker 3: which point we also signed contract agreement with Sanofi and
Speaker 3: then started engaging in the standard phase one healthy volunteer study,
Speaker 3: followed by the very large study in Africa that was
Speaker 3: called by Wildfree and doctor comt in the DRS.
Speaker 1: The historical lack of funding for human African tripanasamiasis and
Speaker 1: all other neglected tropical diseases it has meant that drugs
Speaker 1: are slow to be developed and once available, there are
Speaker 1: many logistical challenges that prevent access by people who need them.
Speaker 1: So can you talk about how important it is to
Speaker 1: form industrial partnerships to connect drug development with setting up
Speaker 1: infrastructure for actually administering those drugs.
Speaker 3: Having a disease that has priority for public health that
Speaker 3: is on the wtual list of diseases that need to
Speaker 3: have you solution is one way of attracting funders together
Speaker 3: with an organization that can bring elements to show it
Speaker 3: can deliver, which was something we did with the development
Speaker 3: of Azak, which in fact we had done also with SENUFI.
Speaker 3: On the other hand, SENUFI, as part of their global
Speaker 3: Corporate Responsibility activity or access to Drug engagement for a
Speaker 3: long time, had been supporting the WHOW financially. Therefore, it
Speaker 3: was kind of a natural partner for us to go
Speaker 3: with SENUFI to engage into this partnership where we would
Speaker 3: be doing the development and looking for funds to do that,
Speaker 3: which we got from public funding as well as private
Speaker 3: funding them doing the manufacturing and distribution together with the
Speaker 3: writ show via a donation of Vaccini as a two
Speaker 3: countries via w O Shoe. So it's a bit complex,
Speaker 3: and I think for each disease it's different, and it's
Speaker 3: clear that we have to continue to promote the need
Speaker 3: to fund research for neglected tropical diseases. But there is
Speaker 3: you know, a kind of move to public health firm
Speaker 3: interest in doing that, although still not as much as
Speaker 3: we have seen for tibing, malaria and HIV.
Speaker 1: So I want to take a quick pause here and
Speaker 1: then when we get back, I want to dive deeper
Speaker 1: into the story of vaccing it as all specifically with
Speaker 1: the clinical trials process. Welcome back everyone. So I was
Speaker 1: wondering if you could talk about what went into the
Speaker 1: clinical trials to test the safety and efficacy of this
Speaker 1: drug and what were some of the biggest challenges in
Speaker 1: conducting these trials.
Speaker 4: This is a good question.
Speaker 2: You know, to conduct technical tyers, you need to go
Speaker 2: where pasions are and those persons are.
Speaker 4: Living in remote areas.
Speaker 2: As you may know, our health facilities in remote areas
Speaker 2: are in very bad states. So the first challenge we
Speaker 2: have many challenges. First, we need to improve those health facilities,
Speaker 2: passion towards laboratory sanitation, all those things, and even to
Speaker 2: put clean waters and electricity by a generator and to
Speaker 2: provide internet connection because this is very important in clinical toil.
Speaker 2: We need to train people because health workers working in
Speaker 2: those remote areas was not very used to clinical trial.
Speaker 2: So we need to train them on a GCP good
Speaker 2: clinical practice, on protocol on how to manage the clinical trial,
Speaker 2: how to manage the adverse events, serious adverss events. So
Speaker 2: we need to trend people on this and we need
Speaker 2: to set up a good way to reach those sites
Speaker 2: because we have local teams, we have National International Team.
Speaker 2: So we need to set up a very safe way
Speaker 2: to reach those remote areas by using safe board, safe
Speaker 2: cards and so on. Eving to set up to all
Speaker 2: those accommodations because when people go there to work, they
Speaker 2: need after the working day to have an acceptable accommodation.
Speaker 2: So we need to set up all this and again
Speaker 2: working on those populations, you know, most of them would
Speaker 2: not be able to read or to be involved or
Speaker 2: to you know, to go in the clinical trial. We
Speaker 2: need to give your UNI to sign an informed consonant form.
Speaker 2: So how to make this at that level for those
Speaker 2: people who could not read, So we set up image
Speaker 2: boxes to explain them clear what is the clinical trial?
Speaker 4: So while they were giving the agreement, there was a
Speaker 4: work of what is it?
Speaker 2: So we need to follow all this and we set
Speaker 2: up all this and again, you know, because we were
Speaker 2: in a clinical trials, we need to provide food to
Speaker 2: those passions. But we were giving food to all hard passions,
Speaker 2: not only for those who was involved in clinical trial.
Speaker 2: So we set up all this and then after we
Speaker 2: start with a clinical trial and with the MANY supervision,
Speaker 2: many follow up. So we work with the national program
Speaker 2: and with the NDI and all our partners with TPH
Speaker 2: that was doing the monitoring.
Speaker 3: So when I joined and I was coming from the
Speaker 3: very well equiped the clinical research networks in Europe US
Speaker 3: and I came to the NDI and here we were,
Speaker 3: you know, with a new chemical entity. We had the
Speaker 3: basic standard package for phase one very good, and then
Speaker 3: we had to start this phase to study where for
Speaker 3: the first time you start treating patients very far away
Speaker 3: and with little access. I would say, to information of
Speaker 3: what was going to happen to patients at the site level,
Speaker 3: And as Wilfrid said, we had to do it where
Speaker 3: patients are and with the only people who know how
Speaker 3: to treat those patients and who are also physicians that
Speaker 3: work in very remote areas. So we had to do
Speaker 3: things that I had not thought before I would need
Speaker 3: to do, which is set up internet connections, come with more,
Speaker 3: you know, bring some equipment that was not there, find
Speaker 3: ways of doing lab tests in a way that would
Speaker 3: not bring something artificial and then living that was not
Speaker 3: the argat. So we had to think with many people
Speaker 3: and it was a collective effort of how can we
Speaker 3: bring the best science in the conditions where we were
Speaker 3: And in addition to everything that Wilfrid said, we had
Speaker 3: to think about this and bring what we thought were
Speaker 3: the best sustainable solutions. We had to do electro undrograms,
Speaker 3: so we took those devices that allow us to have
Speaker 3: direct connection in France with what was happening in the
Speaker 3: middle of the DRC in one patient, etc. So it
Speaker 3: was quite a bit of a stretched effort, but I
Speaker 3: have to say, with so much enthusiasm from everyone everywhere,
Speaker 3: we were all so excited to make it happen. So
Speaker 3: I think we did something really nice that could serve
Speaker 3: as a model for future, you know, research, and that
Speaker 3: also brought a lot of experience to all of us.
Speaker 3: Something else we did a side of this because when
Speaker 3: we said, okay, we need to have this study, as
Speaker 3: any study in the world approved by an ethics committee, Well,
Speaker 3: who's the best position to verify that you're not taking
Speaker 3: risks for patients, that you're responding to your scientific hypothesis,
Speaker 3: that what you're doing is well done, makes sense, you're
Speaker 3: not exposing patients to a risk. And when I joined,
Speaker 3: the routine way was to have a double ethics committee,
Speaker 3: one in the north and one in the south, and
Speaker 3: it was exactly that and we said, well, maybe we
Speaker 3: can do differently, Maybe we can have committees from the
Speaker 3: South and one committee in the North discussing this together
Speaker 3: and finding ways of you know, consolidating different experience from
Speaker 3: different areas of the world in a way that would
Speaker 3: help to have the best review. This is what we
Speaker 3: did and we published and it was a learning experience
Speaker 3: for all of us from those maybe from less experience
Speaker 3: ethics committees in DRC or elsewhere that we're taking a
Speaker 3: huge responsibility in accepting, you know, for the study to
Speaker 3: be conducted in their patients, but also from the committee
Speaker 3: in the North, who were you know, faced with questions
Speaker 3: they had never thought about that you know, made them
Speaker 3: think a bit differently, like you know, funding issues. Are
Speaker 3: colleagues from Africa, we're asking are you sure that you
Speaker 3: will have the funding to continue, or they were asking
Speaker 3: questions about how we explained the study to patients or
Speaker 3: community issues, things like that which they had not ever,
Speaker 3: you know, really experienced. So a very rich experience. And
Speaker 3: then once everything was in, the study was conducted as
Speaker 3: it would be anywhere else, except that we found again
Speaker 3: something which when you have experience in clinical trials you
Speaker 3: wouldn't think is real. We had a follow up of
Speaker 3: patients involved in the study of eighteen months. And you know,
Speaker 3: it is not unusual that one patients are receiving a
Speaker 3: treatment that here was for ten days. Well they come
Speaker 3: after okay, they will come for their follow up visit
Speaker 3: at three months, maybe at six months. A few will
Speaker 3: not come at twelve months, and why the heck would
Speaker 3: they come at eighteen months if they're feeling well. Well,
Speaker 3: we had three I think three patients lost to follow
Speaker 3: up out of over three hundred and ninety patients. This
Speaker 3: is outstanding, outstanding, and everybody has been so impressed by this.
Speaker 3: Why did this happen? Because there was such an effort locally,
Speaker 3: not every in one patients first diagnosed and entered the
Speaker 3: study was followed, and I think again we can explain
Speaker 3: how this was done because it was not simple.
Speaker 2: Yes, you know, clinical trial on hat we need to
Speaker 2: keep those passions. Because the last follow up was eighteen
Speaker 2: months after receiving the treatment. This was not easy, you know,
Speaker 2: because when they feel good, they don't come because they
Speaker 2: are okay, they.
Speaker 4: Receive the treatment.
Speaker 2: The very important moment when we were doing the informed
Speaker 2: content form so that for the award that they need
Speaker 2: to come to all the follow up visits, because if
Speaker 2: you don't come, it's it's considered failure. But we had
Speaker 2: the address, even the name of the leader of their village,
Speaker 2: the name of the head of the news of the village.
Speaker 2: So we have a motorbike to follow them, then cell
Speaker 2: phone number of one of relatives if they have it.
Speaker 4: All these rules, all these to to to reach the
Speaker 4: Greek majority of passions and as we were all motivated
Speaker 4: local team, they are at the national level and at
Speaker 4: our age que. So we we did. We did this
Speaker 4: secess Storian and this acceed but it was not easy
Speaker 4: that we did it.
Speaker 1: Yeah, that's incredible and I can imagine that you know,
Speaker 1: this enormous effort at the national and the local and
Speaker 1: international scales, it's probably led to a lot of lessons
Speaker 1: in terms of, you know, not just how to set
Speaker 1: up clinical trials and how to reach patients and keep
Speaker 1: in contact with them. But I wanted to ask, you know,
Speaker 1: what are the biggest lessons do you think we can
Speaker 1: take from this story affects in it as all, and
Speaker 1: how can we use them to help control efforts for
Speaker 1: other neglected tropical diseases or just general healthcare infrastructure.
Speaker 2: Yes, the great lesson to my side is you know,
Speaker 2: this collaboration because the NDS succeed to put together the
Speaker 2: National Control Program, and that was very important to have
Speaker 2: the National Control Program because they had to give the
Speaker 2: product profile they need, what was the exact need? That
Speaker 2: was the first And to have farmers of course, and
Speaker 2: to have WHO and to have you know, all those
Speaker 2: stakeholders to put them together working on this project.
Speaker 4: That is a great great lesson to my side. So
Speaker 4: it's something we can you know, reproduce, use it.
Speaker 5: When you want to tackle health problem, you need to
Speaker 5: involve the health worker, the control program, the researcher, university WHO,
Speaker 5: and all those takeholders and together.
Speaker 4: We are strong.
Speaker 1: So fixing it as all is currently approved to treat
Speaker 1: the Gambisa form of human African tass which is by
Speaker 1: far the most common form of the disease. But can
Speaker 1: you talk about how far along we are in the
Speaker 1: research to determine whether this drug is also effective against
Speaker 1: Tripanosoma brucei rhodesiense, the other form of human African tanas iass.
Speaker 3: Yes, so we have good news because it took some time,
Speaker 3: but we managed to get funding from EDYCTP, and I
Speaker 3: think I should mention the other founders for the year
Speaker 3: for the HAT program, you know, the Gates Foundation, MSF,
Speaker 3: the Uki government, the French government. I just want to
Speaker 3: mention them because we wouldn't be here without their support.
Speaker 3: But thanks to DYCTP, we were able to start and
Speaker 3: finish recruitment in a small study of vaccinidso tibio DIZNC
Speaker 3: because based on the same studies that showed the potential
Speaker 3: for vaccini desol to work on TIBIGOMNC, we had the
Speaker 3: same information of tibio diziency. So we've just finished a
Speaker 3: moment and I hope that we'll be able to report
Speaker 3: on this quite soon. But it's it's fantastic because because
Speaker 3: the year the reference treatment is melasopol, it's still melaxopol,
Speaker 3: which is this arsenic based treatment. So if we can
Speaker 3: show that vaccini as at can be an alternative to
Speaker 3: a DUG that is yes, very efficicious but also extremely toxic,
Speaker 3: that would be incredibly useful.
Speaker 1: Yes, absolutely, are there other potential applications for vaccine resolve, like,
Speaker 1: for instance, other parasitic diseases besides these tripenosamus.
Speaker 3: So we looked at the swoosh maniasis, and we conducted
Speaker 3: a small study in Sudan which didn't show any efficacy.
Speaker 3: So here we stopped. And then we looked at tragas
Speaker 3: and the signal for guess is not quite clear, so
Speaker 3: I think we have to wait until we have final
Speaker 3: results because that could also be one area of interest.
Speaker 3: Other than that, we've not looked at anything concrete, but
Speaker 3: it's an antiparasity disease, so you know it could have
Speaker 3: other potential potential use.
Speaker 1: So I just have one last question for you, and
Speaker 1: that is what do you hope this next year brings
Speaker 1: in terms of human African trepanees and MIASS research or
Speaker 1: control efforts.
Speaker 4: I think the great step we made is too easy
Speaker 4: the treatment.
Speaker 2: So we moved from melasoport to next, which is the
Speaker 2: kind of god standard.
Speaker 4: But net with Next we.
Speaker 2: Had many challenge, losistical challenge, But now what we have
Speaker 2: we're fixing it as all that can treat both stages,
Speaker 2: and that is tablet is you know, easy to send
Speaker 2: it anywhere in those remote area and it's very easy
Speaker 2: to trend people to use this.
Speaker 4: And this is one of a very important contributions to
Speaker 4: our work toward elimination. I think maybe Nathay can completely No.
Speaker 3: I think first we'd like to see Vaccini as our rollout,
Speaker 3: and we'd like to see, as I said, the results
Speaker 3: of vaccine hudevience. That's one, and see that numbers, you know,
Speaker 3: continue to go down, not as an artifact of patients
Speaker 3: not being fated. But I think what I'd like to
Speaker 3: see is still attention because we know that what people
Speaker 3: call the last mile or to elimination and sustained elimination
Speaker 3: or elimination of transmission takes time. There's another compound in
Speaker 3: our pipeline which is hugely promising as well, a single
Speaker 3: dose treatment, and I think it's just making sure that
Speaker 3: there is still interest. Job is not done, it's not finished.
Speaker 3: There are still patients who need treatment. We need to
Speaker 3: continue the efforts, including to have you know, the commitments
Speaker 3: of countries to continue to be engaged in this, in
Speaker 3: this fight. And in fact this comes really nicely because
Speaker 3: in three days this will be the third MTD, the
Speaker 3: second NTD day, but the third human African tripanusmisis day
Speaker 3: in DRC. So you know, I think it's it's hugely
Speaker 3: important that we do not think that we have finished
Speaker 3: but we are encouraged by our successes and the fact
Speaker 3: that in a way, you know, if, if, if our
Speaker 3: success in HAT can be a kind of reference and
Speaker 3: enthusiastic hope for others to continue to engage in that
Speaker 3: area of enttds will all be really we will have
Speaker 3: double one and fulfilled a bit of our mission.
Speaker 1: Thank you so much to doctor Motombo Cologi and doctor
Speaker 1: Stroborgaft for such a fantastic interview. It is so incredible
Speaker 1: to hear what a game changer effects in it asol
Speaker 1: has been for human African tapanisemiasis and also what this
Speaker 1: drugs development can teach us about the importance of collaborations
Speaker 1: among national control programs, healthcare companies, and global nonprofits for
Speaker 1: the elimination of other neglected tropical diseases. If you want
Speaker 1: to explore more about fecsin it isol or other projects
Speaker 1: that DNDI is involved in, check out their website DNDI
Speaker 1: dot org and I'll also post some links on the
Speaker 1: page for this episode on our website. Also on our
Speaker 1: website you can find all kinds of good stuff, like
Speaker 1: the sources for all of our episodes, transcripts, quarantining and
Speaker 1: plas Brita recipes, our bookshop dot Org affiliate account, links
Speaker 1: to music by Bloodmobile, links to merch our Patreon, alcohol
Speaker 1: free episodes, and so much more. A big thanks as
Speaker 1: always to Bloodmobile, who provides the music for this and
Speaker 1: all of our episodes. And thanks to you listeners. I
Speaker 1: really hope you liked this deep dive into human African
Speaker 1: japanisamiasis and fecsindasol. And a special thank you as always
Speaker 1: to our wonderful patrons. We love you and appreciate you.
Speaker 1: We've got a brand new regular season episode coming out
Speaker 1: next week, so mark your calendars and until then, keep
Speaker 1: washing those hands.
Speaker 3: Ou