S05 E01

Clinical Trials and CNS Research in Canada

1573575279491.jpg

Dr. Angela Genge
Executive Director of Clinical Research Unit
Montreal Neurological Institute

In the first episode of our fifth season, our host Peter Brenders talks with Dr. Angela Genge, Executive Director of the Clinical Research Unit at the Montreal Neurological Institute, about CNS research, recruiting patients for disease trials and the effect of Covid-19 on clinical trials.

LIONA VOX:

 

From the Chronicle Podcast System, this is the NPC Podcast of the National Pharmaceutical Congress, for July 21, 2021. The NPC Podcast was created to discuss and consider the purpose, process and people of the pharma industry during the year of Covid. And today we’re continuing the healthcare conversation by answering questions from listeners, just like you.

 

This program is presented in cooperation with Impres, Canada’s next generation commercial partner. The industry is rapidly evolving and Impres is designed to help you evolve with it. Learn more about Impres tailored best-in-class solutions at www.impres.com.

 

To start our fifth season of podcasts, our guest is Dr. Angela Genge, she is the Executive Director of the Clinical Research Unit at the Montreal Neurological Institute. Dr. Genge will be in conversion with your host, Peter Brender. But first, here is Mitch Shannon, the CEO of Chronicle Companies.

 

Mitch, how is your summer going?

 

MITCH SHANNON (MS):

 

Well Liona, we’re into what Nat King Cole called those lazy, hazy, crazy days. But the work goes on.

 

A lot of the important work in the world of CNS research takes place at the Montreal Neurological Institute. Under the direction of todays’ guest, the institutes Clinical Research Unit established the first of its kind Phase I unit, dedicated to neurological disorders. That includes a long list of conditions that takes in ALS, dementias and other diseases that lack therapies.

 

Here’s Dr. Angela Genge in conversion with Peter.

 

PETER BRENDERS (PB):

 

Welcome to the NPC Podcast. I'm Peter Brenders, your host. In our continuing to look at the purpose, process, and people in pharma in Canada, we will take a look at where pharma first becomes real for patients, the clinical trial. In this episode we will talk with a physician expert who not only has decades of clinical trial and research experience in academic and healthcare settings, but has also worked for a time in the pharmaceutical industry.

 

Joining us today from the Montreal Neurological Institute of McGill University is Dr. Angela Genge, Executive Director of the Clinical Research Unit, the Neuro. 

 

Welcome to the NPC Podcast, Angela.

 

DR. ANGELA GENGE (AG):

 

Thank you, Peter. It's my pleasure to be here.

 

PB:

 

Okay, before we do a deep dive into the mysteries of the clinical trial, I was hoping you could give us an overview of the MNI and some background or history on its clinical trial activities.

 

AG:

 

So the MNI is known as The Neuro. It is a part of McGill University, Faculty of Medicine, and it is a hospital and Research Institute in one building. It was started by the preeminent clinical trialist, Wilder Penfield, who literally used every neurosurgical procedure he did as an opportunity to understand the brain. 

 

My involvement and the involvement of The Neuro in sponsored, pharma sponsored clinical trials, dates back to the late 80s, really, at the time when multiple sclerosis was still untreatable. The unit at that time, started by Dr. Gordon Francis who went on to be critical in the development of one of our best molecules to treat multiple sclerosis, he started a clinical trial unit and became part of all of the early pivotal trials in multiple sclerosis in relapsing remitting Multiple Sclerosis in the early 90s. 

 

This unit then became a larger than MS unit when I started working with Gord after having been trained by him on bringing neuro muscular and ALS clinical trials to The Neuro. The history continues. It's really the history of drug development in neurology and rare disease. And as we develop more and more new and effective therapies for MS, The Neuro began doing more and more trials in neurodegenerative diseases in primary brain tumors, in rare neurological diseases, to where it is now. 

 

And I'm proud to say, in fact, that we have now hit 120 active clinical trials with a very strong focus on rare neurological diseases that are currently not treatable. So I think my passion in this and what's kept me working in drug development and clinical trials since I was a resident under Dr. Francis and helped him out with neuro AIDS clinical trials, if you can think back that far, has been to find therapies in those diseases that are currently not well treated. And for better or worse, that's a lot of Neurology.

 

PB:

 

A couple things you said there sort of make me go wow, or just make you think a bit. One is, you said in the beginning, back when MS didn't have a treatment. And it's funny to think about as we forgot that MS didn't have a treatment in living memory. It wasn't that long ago that there were new treatments and therapies that have come to market to help people and it's a good reminder. It's like, those are drugs. Those are the treatments that are coming out. 

 

You talk about like 120 different sort of therapies and trials. So it's even more, like, can you give me a little bit of context of like, have trials changed over the years?

 

AG:

 

The trials have changed, Peter. When they started, everything was untreatable, except maybe epilepsy. We had some anti epileptics in the 80s. When I started my training in the late 80s, in neurology, MS was an untreatable disease. One of my very first patients when I came to the neuro was a woman who was 29, who actually died of MS. 

 

So think about that. At that same point in history, neuro AIDS was completely fatal. AIDS was fatal. It wasn't HIV with triple therapy, I actually was involved very peripherally with the patients who received the first effective therapies for HIV. MS was actually exactly the same at that time. Two revolutions happen and these revolutions are still happening and are happening now. 

 

One revolution was the magnetic resonance imaging at the time that the therapies were developed for MS. The items on the MRI that we now considered so standard, and we have abilities to digitally, and using AI to do all sorts of massive data interrogation, and make really simple and really clear statements. Those white matter lesions were called UBOs, they were called UBOs because we didn't know what they meant. We were still doing double dose delayed CT scans on MS patients. So that's where it started. 

 

And when we look at what we do now, so MS is like our poster child, for how much you can do when pharma partners with academics who develop new techniques and clinical trialists who have the patience, you get 12 approved therapies for MS. I believe all of this can be applied to rare disease. And I believe we can use the lessons and we are using the lessons to get faster to that point in time, where all rare diseases have the option of being treatable.

 

PB:

 

You're listening to the NPC Podcast, I'm Peter Brenders, your host. 

 

Let's talk about a little bit more recently, in earlier episodes. In our podcast, we've talked to a number of guests on the impact of Covid. What was the effect of Covid on clinical trial activity at The Neuro? Was there an effect?

 

AG:

 

We were pretty unique, the provinces of Quebec that went through a lot of different things with Covid. Early on in January 2020 deemed two hospitals to be non-Covid institutions, us - the Montreal Neurological Institute and hospital - and the Institute of Cardiology were deemed to be non-Covid. What that meant was no Covid positive patients would be transferred to these two institutions. And if someone turned positive with Covid, they were transferred out of the institution. 

 

The reason that was so important is that it allowed us to continue every clinical trial that we have active throughout Covid. We in fact, became a reference center for certain programs, where we were literally at times the only place in the country of Canada, that were open for certain clinical trials. So I consider us blessed that we were able to contain the impact of Covid on The Neuro and therefore, we basically protected all of these clinical trial patients who were dependent on us to continue to participate, to continue to get treatments, we were able to continue that throughout Covid. 

 

Now Quebec is in a very different scene, as you know, but I think we were very blessed. We did have to make a lot of adjustments. Even given that, we were flying people from Vancouver, Calgary, Edmonton, New Zealand, Israel and Italy, during Covid to treat them.

 

PB:

 

Flying internationally, coming into Montreal, do their treatment, fly back. And just. 

 

It's a bit mind boggling to think about the work involved and the cost involved in terms of being able to bring a therapy and give patients that chance to take a look at it. It's like, just the transportation alone is huge.

 

AG:

 

Yeah. We're in an era now. And where we have to use these breakthroughs in therapeutics, some of which have been driven by academia, many of which has been driven by industry, these breakthroughs are really making a difference. For people with rare disease, some of these rare diseases are fatal, so they can't wait for two years for Covid to be over to get their therapy, right. So we need to really do everything we can to focus on getting these breakthrough innovative therapies to the patients who will benefit. 

 

And the other thing we're trying to do is to make that process, and I think some of your listeners have been in the industry for a long time. In rare disease in neurology, I consider us a bit like Star Trek: The Last Frontier. And we're there now, the breakthroughs in ALS therapy, the breakthroughs in gene therapy, the breakthroughs in RNA therapies, neurology is reaping the benefit almost more than any other discipline in those breakthroughs, maybe with the exception of oncology, so we have to be able to get those therapies to the patients.

 

PB:

 

So it seems like you're talking about rare diseases and it seems like rare diseases are becoming more prevalent. Or are we just now starting to see the benefits of research and these new technologies on rare diseases becoming possible treatments? I mean, when I think about it, they're still rare. The patients are still rare, is out there. So how can one centre find enough patients to participate in a trial? 

 

AG:

 

I totally agree with you that there is a fundamental shift. That fundamental shift is coming as a result of several things. The most important thing is innovation in therapies, no question. We couldn't do what we can do for the ALS community. What we're doing now we couldn't do 10 years ago, we couldn't even do five years ago.

 

The second piece that's making rare seem more common, actually, is the patient community itself. They're saying, and they've been saying this for at least a decade, and I would highlight cystic fibrosis, I would highlight some of the rare hematologic conditions. Certainly ALS, the patient groups have said, Hey, wait a second, you can develop another drug for cancer that already has 20 therapies, but we have no therapies. Look at us. And I think a few companies have broken through this 20 years ago, two decades ago, but a lot of interest has come because the patients are advocating for their own care. 

 

You asked how we attract and how a site can attract patients. In fact, in some ways, rare diseases are easier than common diseases. Because in the right setup, in the right clinic, you have a passionate clinician, you have a passionate patient population, who are willing to go wherever they need to go to get into a clinical trial. And you now have the perfect storm because you have biotechs and large pharmas who have identified potential therapies, and the potential of the rare disease market, if you want to put it in business terms, and are investing in it. 

 

So what we do at The Neuro, and I can talk to the network in a minute, is we use every form of communication to let the community and the world know. And our patients are really our partners in this. They have a very vested interest in spreading the word when we have a rare disease trial opening up. 

 

So we do it easily in ALS because of my long standing history. But we've developed, we've gone from zero to 100 in adult SMA patients. We've gotten fully invested in something called vascular scapula humeral dystrophy. We have developed a way of reaching out to patients and we find them and they find us. And they find us from around the world where you know, it's easier if we find them in Quebec, Ontario and New Brunswick, they can drive, but we actually have patients reach out from around the world. They know we're invested in getting patients into clinical trials, that companies know we will find those patients. And we have the experience of running trials now since, I would say 1987, is probably when Gordon started the unit.

 

PB:

 

You're listening to Dr. Angela Genge, Executive Director at The Neuro. 

 

You've got the tools to get the noise out there, to let the patient groups know, though, you have the trials, and then you can bring them together. But I think it's still a bit of a global game. And I think about Canada, like not just the MNI. But even Canada itself. We're a small population in the global sense. 

 

So why does a company bring a trial to the MNI? Why do they bring it here? I mean, is this hard for the MNI to attract them to showcase yourself?

 

AG:

 

You're asking all the right questions, Peter. So there are several things here. One is, I consider it a challenge. But our success speaks for itself. I look at every disease as a new challenge to figure out where the patients are. What we start with is a reputation for executing clinical trials extremely well to being very proactive in getting trials once we are approved through a very traditional feasibility process, which, that's a whole other podcast, what I think about feasability. But once were identified, we are on it. 

 

So we've evolved to an actual startup team with a phenomenal team. But once we know we're getting a trial, we are on it, if that means that we have to push the REB, it's a contract, whatever component of getting a trial started, happens. And we, at the same time, particularly if it's in a disease where we haven't done much work before. So somebody has just come to us with Fragile X. So we don't wait till we have approval to figure out where all the fragile X patients are. We reach out across the country, we see what clinicians follow Fragile X, we see what networks there are. All of this is legal. By the way, all of this is REB approved that we do, we do nothing without having approval.

 

PB:

 

So REB is the research ethics board. So I hear where we’re going, you guys have figured it out. So you've got it down to an art and a science. But I guess the question, I'm still struggling with too, is, alright, so you're the best in class. But if I'm a company internationally, like, why, you know, I hear stuff about Canada, like, why Canada?

 

AG:

 

Absolutely. What, we are 3% of the global pharma market? It's something ridiculously low. And a lot of the way particularly contractors and regulatory assess the different countries are based on stats that don't particularly frame Canada in a good light. But the big thing that I've done, and we've done is to flip the narrative. So if I hear of a program that's not coming to Canada, then I target them if they're within our landscape, not because they don't know that Canada exists at all, but Canada gets deprioritized because of some of our challenges. And so our strengths are often missed, because they're deprioritized before they've actually looked at the situation.

 

PB:

 

So what are those challenges that you say out there? Like, what's the external world seeing in Canada that may not be what reality might look like? Because I think there must be a ton of patients out there that have no idea that Canada doesn't look as pretty as we think we are.

 

AG:

 

Right. So yes, because we have drunk the Kool Aid, Canada has a public health system, it does this and that. What really hinders us, is the size of our population, our geography where the sites are far apart, that has a feature, but much more importantly, particularly in rare disease, the fact that Health Canada never really implemented an orphan disease program or an orphan drug program, means that we've never had the opportunity to publicize how effective Health Canada can be with rare disease. 

 

Then you have the follow on which we all call PMPRB. And it actually is a very short acronym for a very big problem long term. And so companies look at Canada as a difficult sell for a small market. So you basically are fighting a number of battles at that point. So then you really have to go after what matters. What matters is your ability to recruit rare disease patients that have both the network on the patient side, and the ability of sites to deliver on recruitment and deliver in a clinical trial. So the quality of the sites that are seeing rare disease patients in terms, not of their clinical care, but in terms of their clinical trial experience, and setup. And you're still having to promote, what I have actually discovered is a very friendly regulatory environment to rare disease. 

 

So Canada takes a hit because we don't have certain structures. But in fact, because we don't have certain structures in place, particularly the Orphan Drug Act, Health Canada is actually very interested, and has been very friendly towards companies bringing in drugs and rare disease, but that is not very public.

 

PB:

 

Let's close on that high note, then as we think about that, there actually are some positives and some benefits within our system that may not be as well known as we would like them to be, to sort of those industries to bring those products here. What gets you excited about the future?

 

AG:

 

Lots of things. We're established this network called ERADICATE, which is really linking institutions from coast to coast to really upgrade our clinical trial effectiveness across the country. This upgrade will include a lot of efficiencies and really give us the ability to promote Canada for a range of rare diseases, not just the ones I love, but the ones that other people love. 

 

The technologies that are creating the new therapies are mind blowing. They're absolutely mind blowing. We were approached today for a gene therapy FTD trial that they're doing in the US, and they're looking at two sites in Canada. So gene therapy for frontotemporal dementia. It's wild, it's fantastic. 

 

In my lifetime, I expect to see several diseases turned into chronic diseases. I expect ALS, or at least certain populations of ALS patients will go from having a fatal disease to a chronic disease. I think the initial steps we're seeing in Alzheimer's, of frontotemporal dementia will be realized as much more effective therapies. And then I think there are a bunch of rare diseases that are being targeted by the RNAs, hopefully, eventually CRISPR, but patients don't really understand CRISPR. But there are a couple of small companies that have really done exceptionally well at developing RNA therapies. So I think the future is great.

 

PB:

 

So just the little asterisk on that one would be is what we heard through this one, is to make sure that Canadian patients are at the front of the line, not back of the line through sort of our own environment that we create.

 

AG:

 

Absolutely, Peter, that was what got me into ALS trials in 1994. Why should my patients wait?

 

PB:

 

We have been speaking with Dr. Angela Genge, Executive Director at The Neuro on the NPC Podcast. Thank you for listening.

 

MS:

 

Thanks to Dr. Genge and Peter.

 

If you’d like to learn more about her institute, check out www.mcgill.ca/neuro

 

If you have comments or questions about today’s conversation, message us via Twitter @2021NPC. You can also send us an email to health@chronicle.org or phone our comment line at 647-873-6995. If you liked today's podcast, please share it with your colleagues. Find it at Apple iTunes, Google Podcasts, Stitcher, Spotify, or anywhere you look for your podcasts.

 

 The NPC Podcast is presented in cooperation with our good friends at Impres, Canada's next generation commercial partner. Visit them at www.impres.com.

 

This is Mitch Shannon of Chronicle Companies. Podcast Producer for the season is Jeremy Visser and he is assisted by Aria Empakeris. The announcer was Liona Vox. The musical theme is performed with ardour by the NPC Podcast Orchestra under the direction of Maestro Alexi Millbrook. 

 

Stay safe and enjoy the outdoors. We’ll talk again next week.