Episode 21

PLATYPUS: Inside the Pioneering Adaptive Clinical Trial for Progressive MS

On this special episode of The Raw Nerve podcast, recorded at the 2023 Progress in MS Research Conference in Perth, we take a deep dive into PLATYPUS, Australia’s groundbreaking adaptive clinical trial for progressive MS.

Dr Julia Morahan, Head of Research at MS Australia, guides us through a captivating discussion with the brilliant minds steering PLATYPUS—Professor Jeremy Chataway of University College London, Chief Investigator of the UK’s OCTOPUS trial, and Professor Simon Broadley from Griffith University, overseeing PLATYPUS.

Hear the fascinating story behind PLATYPUS’s genesis and how it could reshape the future of progressive MS treatment. The discussion goes into the origins of PLATYPUS and the advantages of its innovative multi-arm, multi-stage trial design, along with the pivotal role played by the MS Community in shaping and overseeing the trial.

As we conclude, our guests share their ultimate dreams of what PLATYPUS and OCTOPUS could ultimately achieve.

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Episode Transcript

Voiceover:

Welcome to The Raw Nerve, the official podcast of MS Australia, a conversation space for all things multiple sclerosis. Join us for news and views on the latest research, treatments and advocacy efforts, as well as candid and informative interviews with our community, those living with MS and their families and carers together with leading clinicians, researchers, and advocates.

Julia Morahan:

Hi everyone. I’m Dr. Julia Morahan, the head of research at MS Australia, and I’m presenting The Raw Nerve, the official podcast of MS Australia today. And I’m delighted to be welcoming two guests, Professor Jeremy Chataway from University College London, and Professor Simon Broadley from Griffith University in Australia.

We’re here today to talk about the new Platypus clinical trial that has launched this week in Australia, which is now part of the amazing Octopus clinical trial that’s been running for a while in the UK. And I have here with me today two eminent professors who are leading each of those projects. Professor Jeremy Chataway from the University College London, and Professor Simon Broadly from Griffith University in Queensland. Starting with you, Jeremy, can you tell us a little bit about Octopus and where the idea for Octopus came from?

Jeremy Chataway:

Yeah, no, thank you very much indeed. It’s great to be here in Perth, in Western Australia. The Octopus program. What we are trying to do is develop new medications for progressive multiple sclerosis, primary, secondary, but progressive multiple sclerosis. And we’re particularly looking at neuro degeneration, neuro repair, remyelination. And looking at molecules, testing molecules in a randomized control trial basis in a trial that will have an effect on progression. And that’s the origin of the Octopus program that we developed in the UK over the last five years. And as you say, we’ve now initiated over the last few months. And we can talk about that over the next few minutes.

Julia Morahan:

Yeah. We have a few different types of MS that we sometimes talk about in terms of the relapsing forms and the progressive forms. Simon, do you want to tell us a little bit about the differences between those two and why we think this trial is going to be so important, particularly for progressive MS?

Simon Broadley:

Sure. We have two broad categories of process in multiple sclerosis. The first is an inflammatory active relapsing component, which most people with MS start off in that phase. Not all, but most. And as the disease progresses through time, more often than not you see people enter a phase where there is progression or disability without relapses particularly.

And there seems to be a relationship between the two. The more inflammatory activity you have, the more likely you are to progress later on. And we have treatments that work very well for the inflammatory phase. They do work, but they don’t work quite as well for the progressive stage. And hence the need now to look at treatments that focus on either reversing or at least slowing down that progressive component of MS.

Julia Morahan:

Yeah. We talk a lot at MS Australia about this really being the holy grail of MS research. This is our great unmet need, being able to treat this cohort of people that really don’t have anything that’s working for them at the moment. This trial is different in terms of its design. Jeremy, do you want to talk a little bit about how this differs from a traditional clinical trial? Because we do have traditional clinical trials going on in progressive MS, but why is this one so exciting?

Jeremy Chataway:

Yes. Yeah, no, you’re right. As you say, we have some but very limited treatments for progressive multiple sclerosis. What we wanted to do was to accelerate the development of new molecules, which could have an effect in progression. And so, we looked around at different trial designs. Classically it’s one-to-one, it’s running a two horse race is a classical clinical trial. But we thought, and we observed and we looked particularly at the cancer world in prostate cancer where there’d really been little progress for many decades.

And then working with a colleague in London, Professor Max Palmer who chairs the MRT clinical trials unit. He’s led what’s called a multi-arm, multi-stage trial, so-called MAMs trial. And again, just using the analogy here, which I think is useful, we’re putting a number of horses into the race. We might start up with three or four horses run the race. And then a certain point, a defined point, we see if those horses have, if you like, overcome the barrier to carry on with that race.

And then if they haven’t, then we’ll take those horses out of the race and then we’ll replace them with new horses. Just using that, I think as a useful analogy as how we start with this multi-arm and multi-stage process. And so, we looked carefully at the work they’ve done in their prostate cancer trial, which has been running now for about 20 years. And has now delivered 10 practice changing results using this sort of process. We thought, “Well, let’s look at that, let’s examine that and then construct a trial along those lines.” And that’s how he came to the Platypus and the Octopus trials.

Julia Morahan:

Yeah, fantastic. And I think the other element that I really like about this design is the fact that we’re looking at repurposed medications. Simon, do you want to explain a little bit about the reason that that’s so important potentially with respect to the design?

Simon Broadley:

Yeah. As Jerry has alluded to, one of the key elements to all of this is to bring new medications to the treatment of progressive MS as quickly as possible. And reutilizing existing drugs that are already licensed for other indications means that the process of seeking approval for those medications to be used as treatment for MS would be much quicker, would be considerably cheaper than developing a completely new therapy.

And so Jeremy and his team undertook an exhaustive exercise of examining all of the evidence for currently available therapies that had any role in causing remyelination, slowing degenerative change in MS or providing neuroprotection. And they involved an international team to do that and picked a list of drugs, which they’ve chosen the first two to go into the Octopus and now the Platypus trial.

Julia Morahan:

Excellent. Do you want to tell us who the winners were?

Simon Broadley:

I might leave that to Jeremy.

Julia Morahan:

Maybe Jeremy can tell us who the-

Jeremy Chataway:

As Simon said we did an exhaustive process and we came up with a top 10 if you like, and we ranked it. And so, the two initial picks are metformin. That’s a drug that’s used in diabetes, it’s a tablet. It’s been around for decades. We know its safety profile, it’s very good. But work done particularly by the Cambridge group in the UK showed that it could have potential regeneration remyelination effects. That’s the first drug.

And the second drug is what’s called lipoic acid. It’s found in low dose sometimes in health foods, but we’re using it in higher dose. And it’s been championed by the group in Oregon in Northwest America. And they did a clinical trial where they showed that, compared to the dummy drug, it reduced the rate of brain change in people with established progressive multiple sclerosis. This was very exciting.

And again, a variety of different mechanisms which we think occur in progression and drive progression. And so we’ve worked with that group, they’re scientific collaborators. We’ve brought that in as the second pick in this trial to see if we can see those results again. And to see over this trial design effects on slowing disability, which of course is where we’re all at to slow, to stop, one day to reverse, but we’ve got to start at the beginning. Those are the two picks which we have in our trial.

Julia Morahan:

Yeah. And very beautiful platform that we can then hopefully have that rolls into the future and then add potentially an increasing numbers of arms as we go.

Jeremy Chataway:

That’s exactly right. And we are on the lookout and a very active process. We have an international committee that looks at emerging new medications from wherever, from laboratories, from pharma companies, biotech, academic groups. We’re open to look at everything. And then we look at the evidence in detail and construct a CV, if you like. We have that as an active progress, an on-rolling progress to look at new arms, new horses, if you like, into the race.

Julia Morahan:

Perfect. I also wanted to touch on, I think one of the really beautiful parts of the design was the involvement of the MS community, and particularly people with MS in the design. Which hasn’t really been a feature potentially of clinical trials in the past and makes this one to me seem so much more accessible and hopefully much more friendly to participants. Can you talk a little bit about your amazing consultation process that you went through?

Jeremy Chataway:

Yeah. really I’m working with the UK MS Society. This was a sort of fundamental part of this trial. And people with multiple sclerosis were involved from the start to the finish. We put together a number of work groups, if you like, looking at drug choice trial design, outcome measurements.

And each of them very much had people with multiple sclerosis involved. And they informed the trial design. They talk about the criteria for coming to trial, the age range, how long people could, if you like, take part in trials, looking at the safety profile, the different medications. They’ve been utterly involved in all of these groups from start to finish.

And now that we’ve constructed it, they remain very much involved. They sit on the oversight committees, they sit on the monthly meetings to examine what’s going on. And we have a pool of extra patients who we can call on to look through particular questions that come our way as we come through trial.

People with multiple sclerosis brokered by the MS Society are a fundamental part of this. And when we speak about our trial, we did it in an international meeting in Canada late last year. A couple of those people with multiple sclerosis came with us to talk about their experiences of designing the trial, being in the trial. And we’ve written that up with them in an article earlier this year.

We’re very committed indeed to involving from the start to the middle, to the finish, people with multiple sclerosis. And it makes the whole process a lot better. It keeps us right on track, the mission that we are all embarking on. And it’s been an entirely positive experience and it’s been great.

Julia Morahan:

Yeah. It’s a wonderful example of a true partnership, honestly, between people with MS and clinicians in order to have the best possible outcome for everybody, which is lovely. And I think something that we should be looking at.

Jeremy Chataway:

Yeah, no, it’s been very important and continues. As I said, it’s not just a one-off. This continues and remains as a fundamental part of this journey as we look to do something more about progression.

Julia Morahan:

Yeah. Excellent. Simon, now we have the Platypus of Octopus. What was it that attracted you to the Octopus model and what are you hoping this will bring to the Australian progressive MS community?

Simon Broadley:

Very much that when we looked at doing an investigator driven trial in Australia focusing on progressive MS, we obviously looked around the world at what was available. And rather than reinvent the wheel, we saw the Octopus trial as being the ideal model to utilize and implement in Australia. And thereby deliver that opportunity for people with progressive MS in Australia to be involved in what is a groundbreaking trial design, a very unique approach. And also with that ultimate goal of delivering a new treatment as soon as possible to people who need it now, not in 10 or 20 years time.

Julia Morahan:

Yep. Excellent. And so Jeremy, your horses are off and racing. How’s it been going?

Jeremy Chataway:

Yeah. It’s been going well. I mean, we’ve got about 100 people already in the trial over the last six, seven months, so that’s fantastic. So far, so good as we’d expect. I mean, that’s the advantage of using repurposed medications. We know them inside out and there are no surprises.

We’ve got great engagement with the community. We’ve got an excellent portal or web portal, so anyone around the UK who’s interested can put in their details. And we’ll look through that automatically and then over the telephone to really engage as many people as possible with progressive multiple sclerosis.

We started and it’s going well. And we just sort of keep the race going. And that’s why it’s such a delight, of course, to come to Australia and for them to be part of this journey and very much lead from Australia with the Platypus work that Simon’s heading up.

Julia Morahan:

Yeah. In parallel, Simon, we have been working very hard behind the scenes before the launch this week to get all of our ducks in a row to try and make this a reality as soon as possible. How are we going with our preparation and when will this be a reality do we think for our population here?

Simon Broadley:

Yeah. We have a few processes to go through with ethics submissions, finalizing the protocol and making sure that all of this is going to work within the Australian environment. We too have engaged with a group of people with MS to help us, guide us through that process, and that’s been very important. But I am hoping sometime early to mid next year, we will be recruiting our first patients into the Platypus trial.

Julia Morahan:

Fantastic. And so exciting. I wanted to ask you each the same question as our final question. But to me, honestly, I think everybody knows I’ve been so excited about this project. I think it is truly going to be one of the legacy pieces that we do as an organization. This is so important. What is your ultimate dream of what Octopus and Platypus could become and be for MS?

Jeremy Chataway:

The dream and the reality we would very much hope is to start to find new medications, to have an effect on progression using this particular process. And we hope very much with a sufficient machine we’ve constructed, it comes sooner rather than later.

And we’ll just keep on going until we are all satisfied, till the community is satisfied that we have done what we need to do with progression, which is to slow, to stop and ultimately repair. We very much think what we put in place here is a long-term platform, as they say, so that we can derive different medications, the best medications in the world, the best laboratories in the world to take them through, to translate them into. We trial them and we find those effects as beneficial effects on human beings with progressive multiple sclerosis.

Simon Broadley:

Yeah, I would hope it almost becomes a rolling program and almost becomes the normal standard of care that at any given time we will be utilizing what we consider to be the best therapies available at that point in time. But then looking to also introduce new potential therapies alongside those going into the future such that we’re continually optimizing.

Jeremy Chataway:

Yeah. That’s right.

Simon Broadley:

And individualizing treatment as time goes by.

Jeremy Chataway:

Yeah, yeah. Improving all the time the standard of care for people with progressive MS.

Julia Morahan:

Yeah, I think the design has that aspect for me where it’s almost infinite that you could continually evolve to make improvements and make sure that everybody is being [inaudible 00:18:04].

Jeremy Chataway:

Safe in the knowledge it’s done on a strict scientific, well-governed, clinically oversight basis, so what comes out is the truth, and we know that medications work or don’t work.

Simon Broadley:

Yeah. Because it’s equally as important to just know that something unfortunately doesn’t work.

Jeremy Chataway:

Yeah. Exactly.

Julia Morahan:

Well, I think MS Australia is incredibly proud to be part of this journey. And we want to thank both of you so much for everything that you have done to make this a reality. And I’m so excited to see where it leads.

Jeremy Chataway:

And I have to say from the Octopus UK side, it’s a massive thing to be part of this. And we are so excited. And it’s the start of course, of a great partnership. And really, it’s fantastic for me here to be in Perth to share in Platypus, Octopus with you.

Julia Morahan:

Well, thank you so much for being here.

Voiceover:

Thanks for listening to The Raw Nerve, the official podcast of MS Australia. To hear more, subscribe to our podcast today at msaustralia.org.au/podcast.

Views expressed on the Raw Nerve Podcast, including any discussions or reference to medications or treatments by podcast guests, do not necessarily represent the views of MS Australia and should not be seen as either an endorsement or rejection of a treatment.

 MS Australia does not recommend any specific treatment for people living with MS. Decisions about any treatments, taking into consideration the potential benefits and side effects for each individual’s circumstances, should be made in careful consultation with the person’s neurologist.

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PLATYPUS: Inside the Pioneering Adaptive Clinical Trial for Progressive MS