Episode Transcript
[00:00:00] Speaker A: Hello, My name is Dr. Hugo Penny. I'm a consultant gastroenterologist at Sheffield Teaching Hospitals. I'm delighted to be here today with Dr. Michael Fitzpatrick, who's a consultant gastroenterologist at Oxford.
Michael, we've just had a really great session on small bowel and intestinal diseases focusing on celiac disease.
And your talk was great at illustrating some of the new treatments that may become available for people with celiac disease. The gluten free diet has been established for decades.
But Michael, why might we need a new treatment for people with celiac disease?
[00:00:39] Speaker B: Thanks, Hugo. It was a really great session. It was super to see so many people attending and interested in coeliac disease and a great series of talks. So we've had the gluten free diet for 73 years and. And if the gluten free diet was a drug, we would complain about it because we see a good chunk of patients who have ongoing symptoms despite a gluten free diet, patients who have ongoing villus atrophy and intestinal changes despite the treatment. And for many it's poorly tolerated and it's a pretty inequitable treatment.
So while the gluten free diet is sufficient for many of our patients, there are certainly a subset of patients who have ongoing symptoms or ongoing villous atrophy where new treatments are really needed.
[00:01:28] Speaker A: Absolutely. And in your talk, you illustrated several different classes of medication that are being developed at the moment.
What sort of areas around the sort of from eating gluten through to developing the response are they trying to target?
[00:01:43] Speaker B: Yeah, I think we're at a really exciting time where there's actually quite a well developed therapeutic pipeline of different classes of drugs.
There are a group of medications that are in development that I think are quite familiar for those who manage things like inflammatory bowel disease that are targeting cytokine pathways and so on that are involved in celiac disease, so targeting things like IL15.
But there are a range of medications that are really exciting that are targeting the antigen itself. Because the great thing about celiac disease is it's an autoimmune condition where we know what causes it, we know the antigen itself. And so there are treatments that are looking to break down gluten, tablets that would break down gluten in the diet, ones that would block it being altered by this enzyme, tissue transglutaminase, ones that would block it being sensed by the immune system, and also what are called tolerogenic therapies that aim to reprogram the immune response to gluten and induce immune tolerance to it. So a number of drug classes that are quite different from what we see in inflammatory bowel disease.
[00:02:50] Speaker A: Yeah, that's fascinating, isn't it? And like you say, so the pitch for the kind of person that that might be suitable for would probably range depending on the type of target of the treatment itself. But generally you were saying people who are struggling with the gluten free diet or with persisting symptoms or phylos atrophy. That's where we're thinking we might, we could see this in the future in clinic.
[00:03:14] Speaker B: Yes. So patients who are doing their best job as they possibly can with a gluten free diet, but probably too much gluten is getting into their diet, whatever they do.
Patients who have refractory celiac disease, which we can talk about, and patients who perhaps get really bad symptoms with inadvertent gluten exposure, so find themselves getting gluten while eating out or while traveling. And often that is very disabling for patients and it really stops them from living a full life.
[00:03:44] Speaker A: Absolutely. And that's interesting, isn't it, because we're at this position, like you say, where we're being able to maybe open up different therapies for people and different groups of people with celiac disease, like you say, refractory celiac disease. We do use some treatments for.
Could you expand a little bit on that?
[00:04:01] Speaker B: Well, we had a couple of great talks in the session about that. We've got patients who have this refractory celiac disease type 1, which looks like ongoing activation, very much like standard active celiac disease from gluten exposure, but in someone on a gluten free diet. And there, there was a great talk talking about the role of budesonide as a therapy.
And then there is this other condition called refractory celiac disease type 2, which is a pre lymphoma condition. And there, there are a range of therapies, including chemotherapeutic agents that we can use for, to treat that condition and reduce the risk of lymphoma development. But it would be great to have other targeted therapies. And there is promise from a class of medications, the JAK inhibitors, which look like they could be promising targets in refractory coeliac disease.
[00:04:52] Speaker A: And we do try and utilise the medications that we have available for those complex coeliac patients at the moment.
And that's really useful. And going back, as we were just saying, to the novel class, the new development of the new medications that are being developed, drug Discovery and developments are very convoluted and timely process.
Whereabouts are we up to with some of those medications that you were mentioning?
[00:05:21] Speaker B: Yes, it is difficult and I think one of the challenges with coeliac disease is because we do not have any licensed therapies, we haven't got a roadmap for how drugs should be developed, what phase three trial should look like and what the outcomes that a regulator would require are.
But we currently have multiple assets that are in phase 2 clinical trials. So those are early trials of efficacy.
And there are multiple trials, particularly in the us, but several that are running in Europe and the uk, including ones that Sheffield and Oxford have been involved in. So agents such as an agent that blocks tissue, transglutaminase 2, and its action is currently in late phase 2 clinical trials. And that one looks really promising. And there have been a couple of trials of these tolerogenic therapies and we're sort of awaiting the results of those phase 2a and 2b trials. So most of the agents that are currently along the pipeline are in early phase 2 clinical trials.
[00:06:27] Speaker A: Of the several that we talked about, you talked about in your talk, is it too early to stick our necks out and say there might be promise with one or I'm not going to
[00:06:40] Speaker B: make any predictions because I'll probably be wrong. However, I think the ones that are most advanced and have the strongest data to date is the anti tissue transglutaminase ones, which have some solid data from phase 2a clinical trials and are now going into larger phase 2b clinical trials. And some of these tolerogenic therapies that had some promising data in early phase 2a trials. But it's probably a little bit too early to see whether the reality will kind of meet the promise of those agents.
[00:07:14] Speaker A: Absolutely. Many a slip between the cup and the lip in terms of the ages of the people being enrolled in the trials. I mean, is it mainly adults who we think that these therapies will be for or would this be available to children, do we think as well?
[00:07:34] Speaker B: Well, I think in terms of the trials, often trials really focus on adult patients. So the ones that we've been involved with have either had an age cut off of 16 or 18 and have really been focused on adult patients with diagnosed coeliac disease, have been on a gluten free diet for 12 months or more and have got ongoing symptoms related to their coeliac disease and ongoing evidence of some damage on duodenal biopsy. So there's some ongoing villous atrophy as well as symptoms. And that's what most of the trials at the moment are focused on. But I think in future, there are other populations. I think the paediatric population is really important in coeliac disease, as are patients who maybe have quite well controlled coeliac disease but get terrible symptoms on gluten exposure. And that's another group of people who therapies could be used for in the future.
[00:08:26] Speaker A: It's certainly an exciting area. We're up to some phase two with some potential contenders.
Let's see and watch this space. Thank you very much. Pleasure for talking this morning.
