Vivienne Parry, Professor Bill Newman, Anita Hanson and Professor Matt Brown: Can genomic testing prevent adverse drug reactions?

Pharmacogenomics plays a critical role in personalised medicine,
as some adverse drug reactions are genetically determined.
Adverse drugs reactions (ADRs) account for 6.5% of hospital
admissions in the UK, and the application of pharmacogenomics to
look at an individuals response to drugs can significantly
enhance patient outcomes and safety.


In this episode, our guests discuss how genomic testing can
identify patients who will respond to medications and those who
may have adverse reactions. We hear more about Genomics England's
collaboration with the Medicines and Healthcare products
Regulatory Agency in the Yellow Card Biobank and our guests
discuss the challenges of implementing pharmacogenomics into the
healthcare system.


Our host Vivienne Parry, Head of Public Engagement at Genomics
England, is joined by Anita Hanson, Research Matron and the Lead
Research Nurse for clinical pharmacology at Liverpool University
Hospitals NHS Foundation Trust, and Professor Bill Newman,
Professor of translational genomic medicine at the Manchester
Center for Genomic Medicine, and Professor Matt Brown, Chief
Scientific Officer at Genomics England.


 


"I think we’re moving to a place where, rather than just doing
that one test that might be relevant to one drug, we’d be able to
do a test which at the same price would generate information that
could be relevant at further points in your life if you were
requiring different types of medicine. So, that information would
then be available in your hospital record, in your GP record,
that you could have access to it yourself. And then I think
ultimately what we would really love to get to a point is where
everybody across the whole population just has that information
to hand when it’s required, so that they’re not waiting for the
results of a genetic test, it’s immediately within their
healthcare record."


 


You can watch this video learn more about Jane's lived experience
with Stevens-Johnson syndrome, on The Academy of Medical
Sciences' (AMS) YouTube channel. The story, co-produced by Areeba
Hanif from AMS, provides an in-depth look at Jane's journey.


Want to learn more about personalised medicine? Listen to our
Genomics 101 episode where Professor Matt Brown explains what it
is in less than 5 minutes: Genomics 101: What is personalised
medicine? 


You can download the transcript or read it below.


Vivienne: Hello and welcome to Behind the Genes. 


Bill: What we’ve seen is that the limited adoption so far in the
UK and other countries has focused particularly on severe adverse
drug reactions. They’ve been easier to identify and there’s a
clear relationship between some drugs and some genetic changes
where that information is useful. So, a good example has been the
recent adoption of pharmacogenetic testing for a gene called DPYD
for patients undergoing cancer treatment, particularly breast and
bowel cancer. And if you have an absence of the enzyme that that
gene makes, if you’re given that treatment, then you can end up
on intensive care and die, so it’s a really significant side
effect. But as you say, the most common side effects aren’t
necessarily fatal, but they can have a huge impact upon people
and on their wellbeing. 


Vivienne: My name’s Vivienne Parry and I’m head of public
engagement at Genomics England, and today we’ll be discussing the
critical role of pharmacogenomics in personalised medicine,
highlighting its impact on how well medicines work, their safety,
and on patient care. I’m joined today by Professor Bill Newman,
professor of translational genomic medicine at the Manchester
Centre for Genomic Medicine, Anita Hanson, research matron, a
fabulous title, and lead research nurse for clinical pharmacology
at the Liverpool University Hospital’s NHS Foundation Trust, and
Professor Matt Brown, chief scientific officer for Genomics
England. And just remember, if you enjoy today’s episode, we’d
love your support, so please like, share and rate us on wherever
you listen to your podcasts. 


So, first question to you, Bill, what is pharmacogenomics? 


Bill: Thanks Viv. I think there are lots of different
definitions, but how I think of pharmacogenetics is by using
genetic information to inform how we prescribe drugs, so that
they can be safer and more effective. And we’re talking about
genetic changes that are passed down through families, so these
are changes that are found in lots of individuals. We all carry
changes in our genes that are important in how we transform and
metabolise medicines, and how our bodies respond to them. 


Vivienne: Now, you said pharmacogenetics. Is it one of those
medicine things like tomato, tomato, or is there a real
difference between pharmacogenetics and pharmacogenomics? 


Bill: So, people, as you can imagine, do get quite irate about
this sort of thing, and there are lots of people that would
contest that there is a really big important difference. I
suppose that pharmacogenetics is more when you’re looking at
single changes in a relatively small number of genes, whereas
pharmacogenomics is a broader definition, which can involve
looking at the whole genome, lots of genes, and also whether
those genes are switched on or switched off, so the expression
levels of those genes as well would encompass pharmacogenomics.
But ultimately it’s using genetic information to make drug
prescription safer and more effective. 


Vivienne: So, we’re going to call it pharmacogenomics and we’re
talking about everything, that’s it, we’ll go for it. So Matt,
just explain if you would the link between pharmacogenomics and
personalised medicine. And I know that you’ve done a big Genomics
101 episode about personalised medicine, but just very briefly,
what’s the link between the two? 


Matt: So, personalised medicine’s about using the right dose of
the right drug for the right individual. And so pharmacogenomics
helps you with not only ensuring that you give a medication which
doesn’t cause problems for the person who receives it, so an
adverse drug reaction, but also that they’re actually getting the
right dose. Of course, people’s ability to metabolise, activate
and respond to drugs genetically is often genetically determined,
and so sometimes you need to adjust the dose up or down according
to a person’s genetic background. 


Vivienne: Now, one of the things that we’ve become very aware of
is adverse drug reactions, and I think they account for something
like six and a half percent of all hospital admissions in the UK,
so it’s absolutely huge. Is that genetically determined adverse
drug reactions? 


Matt: So, the answer to that is we believe so. There’s quite a
bit of data to show that you can reduce the risk of people
needing a hospital admission by screening genetic markers, and a
lot of the very severe reactions that lead to people being
admitted to hospital are very strongly genetically determined. So
for example, there are HLA types that affect the risk of adverse
drug reactions to commonly used medications for gout, for
epilepsy, some HIV medications and so on, where in many health
services around the world, including in England, there are
already tests available to help prevent those leading to severe
reactions. It’s likely though that actually the tests we have
available only represent a small fraction of the total
preventable adverse drug reactions were we to have a formal
pre-emptive pharmacogenomics screening programme. 


Vivienne: Now, I should say that not all adverse drug reactions
are genetic in origin. I mean, I remember a rather nasty incident
on the night when I got my exam results for my finals, and I’d
actually had a big bee sting and I’d been prescribed
antihistamines, and I went out and I drank rather a lot to
celebrate, and oh my goodness me, I was rather ill [laughter].
So, you know, not all adverse drug reactions are genetic in
origin. There are other things that interact as well, just to
make that clear to people. 


Matt: Yes, I think that’s more an interaction than an adverse
drug reaction. In fact frankly, the most common adverse drug
reaction in hospitals is probably through excess amounts of
water, and that’s not medically determined, that’s the
prescription. 


Vivienne: Let me now come to Anita. So, you talk to patients all
the time about pharmacogenomics in your role. You’ve been very
much involved in patient and public involvement groups at the
Wolfson Centre for Personalised Medicine in Liverpool. What do
patients think about pharmacogenomics? Is it something they
welcome? 


Anita: I think they do welcome pharmacogenomics, especially so
with some of the patients who’ve experienced some of the more
serious, life threatening reactions. And so one of our patients
has been doing some work with the Academy of Medical Sciences,
and she presented to the Sir Colin Dollery lecture in
2022, and she shared her story of having an adverse drug reaction
and the importance of pharmacogenomics, and the impact that
pharmacogenomics can have on patient care. 


Vivienne: Now, I think that was Stevens-Johnson syndrome. We’re
going to hear in a moment from somebody who did experience
Stevens-Johnson’s, but just tell us briefly what that is. 


Anita: Stevens-Johnson syndrome is a potentially life threatening
reaction that can be caused by a viral infection, but is more
commonly caused by a medicine. There are certain groups of
medicines that can cause this reaction, such as antibiotics or
anticonvulsants, nonsteroidal anti-inflammatories, and also a
drug called allopurinol, which is used to treat gout. Patients
have really serious side effects to this condition, and they’re
often left with long-term health complications. The morbidity and
mortality is considerable as well, and patients often spend a lot
of time in hospital and take a long time to recover.  


Vivienne: And let’s now hear from Jane Burns for someone with
lived experience of that Stevens-Johnson syndrome. When Jane
Burns was 19, the medicine she took for her epilepsy was
changed. 


Jane: I remember waking up and feeling really hot, and I was
hallucinating, so I was taken to the Royal Liverpool Hospital
emergency department by my parents. When I reached A&E, I had
a temperature of 40 degrees Celsius. I was given Piriton and
paracetamol, and the dermatologist was contacted. My mum had
taken my medication to hospital and explained the changeover
process with my epilepsy medication. A decision was made to
discontinue the Tegretol and I was kept in for observation. Quite
rapidly, the rash was changing. Blisters were forming all over my
body, my mouth was sore and my jaw ached. My temperature remained
very high. It was at this point that Stevens-Johnson syndrome, or
SJS, was diagnosed. 


Over the next few days, my condition deteriorated rapidly. The
rash became deeper in colour. Some of the blisters had burst, but
some got larger. I developed ulcers on my mouth and it was
extremely painful. I started to lose my hair and my fingernails.
As I had now lost 65 percent of my skin, a diagnosis of toxic
epidermal necrolysis, or TEN, was made. Survivors of SJS TEN
often suffer with long-term visible physical complications, but
it is important to also be aware of the psychological effects,
with some patients experiencing post-traumatic stress disorder.
It’s only as I get older that I realise how extremely lucky I am
to have survived. Due to medical and nursing expertise, and the
research being conducted at the time, my SJS was diagnosed
quickly and the medication stopped. This undoubtedly saved my
life. 


Vivienne: Now, you’ve been looking at the development of a
passport in collaborating with the AMS and the MHRA. Tell me a
bit more about that. 


Anita: Yes, we set up a patient group at the Wolfson Centre for
Personalised Medicine approximately 12 years ago, and Professor
Sir Munir Pirmohamed and I, we wanted to explore a
little bit more about what was important to patients, really to
complement all the scientific and clinical research activity
within pharmacogenomics. And patients recognised that, alongside
the pharmacogenomic testing, they recognised healthcare
professionals didn’t really have an awareness of such serious
reactions like Stevens-Johnson syndrome, and so they said they
would benefit from having a My SJS Passport, which is a booklet
that can summarise all of the important information about their
care post-discharge, and this can then be used to coordinate and
manage their long-term healthcare problems post-discharge and
beyond. And so this was designed by survivors for survivors, and
it was then evaluated as part of my PhD, and the findings from
the work suggest that the passport is like the patient’s voice,
and it really does kind of validate their diagnosis and raises
awareness of SJS amongst healthcare professionals. So, really
excellent findings from the research, and the patients think it's
a wonderful benefit to them. 


Vivienne: So, it’s a bit like a kind of paper version of the
bracelet that you sometimes see people wearing that are on
steroids, for instance. 


Anita: It is like that, and it’s wonderful because it’s a
handheld source of valuable information that they can share with
healthcare professionals. And this is particularly important if
they’re admitted in an emergency and they can’t speak for
themselves. And so the passport has all that valuable
information, so that patients aren’t prescribed that drug again,
so it prevents them experiencing a serious adverse drug reaction
again.  


Vivienne: So, Stevens-Johnson, Bill, is a really scary side
effect, but what about the day to day benefits of
pharmacogenomics for patients? 


Bill: So, what we’ve seen is that the limited adoption so far in
the UK and other countries has focused particularly on severe
adverse drug reactions. They’ve been easier to identify and
there’s a clear relationship between some drugs and some genetic
changes where that information is useful. So a good example has
been the recent adoption of pharmacogenetic testing for a gene
called DPYD for patients undergoing cancer treatment,
particularly breast and bowel cancer. And if you have an absence
of the enzyme that that gene makes, if you’re given that
treatment, then you can end up on intensive care and die, so it’s
a really significant side effect. But as you say, the most common
side effects aren’t necessarily fatal, but they can have a huge
impact upon people and on their wellbeing.  


And it’s not just in terms of side effects. It’s in terms of the
effectiveness of the medicine. Because if a person is prescribed
a medicine that doesn’t or isn’t going to work for them then it
can take them longer to recover, to get onto the right medicine.
That can have all sorts of detrimental effects. And so when we’re
thinking about introducing pharmacogenetics more broadly rather
than just on a single drug or a single gene basis, we’re thinking
about that for common drugs like antidepressants, painkillers,
statins, the drugs that GPs are often prescribing on a regular
basis to a whole range of patients. 


Vivienne: So, to go back to you, Anita, we’re really talking
about dose here, aren’t we, whether you need twice the dose or
half the dose depending on how quickly your body metabolises that
particular medicine. How do patients view that? 


Anita: Well, the patient in question who presented for the
Academy of Medical Sciences, I mean, her take on this was, she
thinks pharmacogenetics is wonderful because it will allow
doctors and nurses to then prescribe the right drug, but also to
adapt the dose accordingly to make sure that they get the best
outcome, which provides the maximum benefit while also minimising
any potential harm. And so from her perspective, that was one of
the real benefits of pharmacogenomics. But she also highlighted
about the benefits for future generations, the fear of her son
taking the same medicine and experiencing the same reaction. And
so I think her concerns were, if we have pharmacogenetic testing
for a panel of medicines, as Bill mentioned then, then perhaps
this would be fantastic for our children as they grow up, and we
can identify and predict and prevent these type of reactions
happening to future generations. 


Vivienne: And some of these drugs, Bill, are really very common
indeed, something like codeine. Just tell us about codeine, ‘cos
it’s something – whenever I tell this to friends [laughter],
they’re always completely entranced by the idea that some people
don’t need nearly as much codeine as others. 


Bill: Yeah, so codeine is a drug that’s very commonly used as a
painkiller. To have its real effect, it needs to be converted in
the body to a different drug called morphine, and that is done by
an enzyme which is made by a gene called CYP2D6. And we all carry
changes in CYP2D6, and the frequency of those variants, whether
they make the gene work too much or whether they make it work too
little, they vary enormously across the world, so that if you go
to parts of Africa, about 30 percent of the population will make
more of the CYP2D6, and so they will convert the codeine much
more quickly, whereas if you go to the UK, maybe up to ten
percent of the white population in the UK just won’t be
converting codeine to morphine at all, so they won’t get any
benefit from the drug. So at both ends, you have some people that
don’t respond and some people that respond a little bit too much
so that they need either an alternative drug or they need a
different dose. 


Vivienne: So, all those people who say, you know, “My headache
hasn’t been touched by this painkiller,” and we say, “What a wimp
you’re being,” actually, it’s to do with genetics. 


Bill: Yeah, absolutely. There’s a biological reason why people
don’t – not for everybody, but for a significant number of
people, that’s absolutely right, and we can be far more tailored
in how we prescribe medication, and get people onto painkillers
that work for them much more quickly. 


Vivienne: And that’s so interesting that it varies by where you
come from in the world, because that means we need to give
particular attention – and I’m thinking, Anita, to working with
patients from different community groups, to make sure that they
understand the need for pharmacogenomics. 


Anita: I think that’s really important, Vivienne, and I think we
are now having discussions with the likes of Canada SJS awareness
group, and also people have been in touch with me from South
Africa because people have requested the passport now to be used
in different countries, because they think it’s a wonderful tool,
and it’s about raising awareness of pharmacogenomics and the
potential benefits of that, and being able to share the tools
that we’ve got to help patients once they’ve experienced a
serious reaction. 


Vivienne: So, pharmacogenomics clearly is important in the
prevention of adverse drug reactions, better and more accurate
prescribing, reduced medicines wastage. Does this mean that it’s
also going to save money, Bill, for the NHS? 


Bill: Potentially. It should do if it’s applied properly, but
there’s lots of work to make sure that not only are we using the
right evidence and using the right types of tests in the
laboratory, but we’re getting the information to prescribers, so
to GPs, to pharmacists, to hospital doctors, in a way that is
understandable and meaningful, such that they can then act upon
that information. So, the money will only be saved and then can
be reused for healthcare if the whole process and the whole
pathway works, and that information is used effectively. 


Vivienne: So, a lot of research to make sure that all of that is
in place, and to demonstrate the potential cost savings. 


Bill: Yes. I mean, there are very nice studies that have been
done already in parts of the world that have shown that the
savings that could be accrued for applying pharmacogenetics
across common conditions like depression, like in patients to
prevent secondary types of strokes, are enormous. They run into
hundreds of millions of pounds or dollars. But there is an
initial investment that is required to make sure that we have the
testing in place, that we have the digital pathways to move the
information in place, and that there’s the education and
training, so that health professionals know how to use the
information. But the potential is absolutely enormous. 


Vivienne: Matt, can I turn now to the yellow card. So, people
will be very familiar with the yellow card system. So, if you
have an adverse reaction, you can send a yellow card in – I mean,
literally, it is a yellow card [laughter]. It does exactly what
it says on the tin. You send a yellow card to the MHRA, and they
note if there’s been an adverse effect of a particular medicine.
But Genomics England is teaming up with the MHRA to do something
more with yellow cards, and we’re also doing this with the Yellow
Card Biobank. Tell us a bit more. 


Matt: So, yellow card’s a great scheme that was set up decades
ago, initially starting off, as you said, with literally yellow
cards, but now actually most submissions actually come online.
And it’s important to note that submissions can come not just
from healthcare providers, but majority of submissions actually
come from patients themselves, and that people should feel free,
if they feel they’ve had an adverse drug reaction, to report that
themselves rather than necessarily depending on a medical
practitioner or the healthcare provider to create that report.
So, Genomics England is partnering with the MHRA in building
what’s called the Yellow Card Biobank, the goal of which is to
identify genetic markers for adverse drug reactions earlier than
has occurred in the past, so that we can then introduce genetic
tests to prevent these adverse drug reactions much sooner than
has occurred previously.  


So, what we’re doing is basically at the moment we’re doing a
pilot, but the ultimate plan is that in future, patients who
report a serious adverse drug reaction through the Yellow Card
Biobank will be asked to provide a sample, a blood sample, that
we then screen. We do a whole genome sequence on it, and then
combine these with patients who’ve had like adverse drug
reactions and identify genetic markers for that adverse drug
reaction medication earlier, that can then be introduced into
clinical practice earlier. And this should reduce by decades the
amount of time between when adverse drug reactions first start
occurring with medications and us then being able to translate
that into a preventative mechanism. 


Vivienne: And will that scheme discover, do you think, new
interactions that you didn’t know about before? Or do you expect
it to turn up what you already know about? 


Matt: No, I really think there’s a lot of discovery that is yet
to happen here. In particular, even for drugs that we know cause
adverse drug reactions, mostly they’ve only been studied in
people of European ancestry and often in East Asian ancestry, but
in many other ancestries that are really important in the global
population and in the UK population, like African ancestry and
South Asian ancestries, we have very little data. And even within
Africa, which is an area which is genetically diverse as the rest
of the world put together, we really don’t know what different
ethnicities within Africa, actually what their genetic background
is with regard to adverse drug reactions. 


The other thing I’d say is that there are a lot of new
medications which have simply not been studied well enough. And
lastly, that at the moment people are focused on adverse drug
reactions being due to single genetic variants, when we know from
the model of most human diseases that most human diseases are
actually caused by combinations of genetic variants interacting
with one another, so-called common disease type genetics, and
that probably is similarly important with regard to
pharmacogenomics as it is to overall human diseases. That is,
it’s far more common that these are actually due to common
variants interacting with one another rather than the rare
variants that we’ve been studying to date. 


Vivienne: So, it’s a kind of cocktail effect, if you like. You
know, you need lots of genes working together and that will
produce a reaction that you may not have expected if you’d looked
at a single gene alone. 


Matt: That’s absolutely correct, and there’s an increasing amount
of evidence to show that that is the case with medications, but
it’s really very early days for research in that field. And the
Yellow Card Biobank will be one of many approaches that will
discover these genetic variants in years to come. 


Vivienne: Now, Matt’s a research scientist. Bill, you’re on the
frontline in the NHS. How quickly can this sort of finding be
translated into care for people in the NHS? 


Bill: So, really quickly is the simple answer to that, Viv. If we
look at examples from a number of years ago, there’s a drug
called azathioprine that Matt has used lots in some of his
patients. In rheumatology, it’s used for patients with
inflammatory bowel disease. And the first studies that showed
that there was a gene that was relevant to having bad reactions
to that drug came out in the 1980s, but it wasn’t until well into
this century, so probably 30-plus years later that we were
routinely using that test in clinical medicine. So, there was an
enormous lot of hesitancy about adopting that type of testing,
and a bit of uncertainty. If you move forward to work that our
colleague Munir Pirmohamed in Liverpool has done with colleagues
in Australia like Simon Mallal around HIV medicine, there was
this discovery that a drug called abacavir, that if you carried a
particular genetic change, that you had a much higher risk of
having a really severe reaction to that. The adoption from the
initial discovery to routine, worldwide testing happened within
four years.  


So, already we’ve seen a significant change in the appetite to
move quickly to adopt this type of testing, and I see certainly
within the NHS and within other health systems around the world,
a real desire to adopt pharmacogenetics into routine clinical
practice quickly and at scale, but also as part of a broader
package of care, which doesn’t just solely focus on genetics, but
thinks about all the other parts that are important in how we
respond to medication. So, making sure we’re not on unusual
combinations of drugs, or that we’re taking our medicine at the
right time and with food or not with food, and all of those other
things that are really important. And if you link that to the
pharmacogenetics, we’re going to have a much safer, more
effective medicines world. 


Vivienne: I think one of the joys of working at Genomics England
is that you see some of this work really going into clinical
practice very fast indeed. And I should say actually that the
Wolfson Centre for Personalised Medicine, the PPI group that
Anita looks after so well, they’ve been very important in
recruiting people to Yellow Card Biobank. And if anyone’s
listening to this, Matt, and wants to be part of this, how do
they get involved? Or is it simply through the yellow card? 


Matt: So at the moment, the Yellow Card Biobank is focusing on
alopurinol.  


Vivienne: So, that’s a medicine you take for gout. 


Matt: Which I use a lot in my rheumatology clinical practice. And
direct acting oral anticoagulants, DOACs, which are used for
vascular disease therapies and haemorrhage as a result of that.
So, the contact details are available through the MHRA website,
but I think more importantly, it’s just that people be aware of
the yellow card system itself, and that if they do experience
adverse drug reactions, that they do actually complete a report
form, ‘cos I think still actually a lot of adverse drug reactions
go unreported. 


Vivienne: I’m forgetting of course that we see Matt all the time
in the Genomics England office and we don’t think that he has any
other home [laughter] than Genomics England, but of course he
still sees some patients in rheumatology clinic. So, I want to
now look to the future. I mean, I’m, as you both know, a huge
enthusiast for pharmacogenomics, ‘cos it’s the thing that
actually, when you talk to patients or just the general public,
they just get it straight away. They can’t think why, if you knew
about pharmacogenomics, why you wouldn’t want to do it. But it’s
not necessarily an easy thing to do. How can we move in the
future, Bill, to a more proactive approach for pharmacogenomics
testing? Where would we start? 


Bill: Yes, so I think we’ve built up really good confidence that
pharmacogenetics is a good thing to be doing. Currently, we’re
doing that predominantly at the point when a patient needs a
particular medicine. That’s the time that you would think about
doing a genetic test. And previously, that genetic test would
only be relevant for that specific drug. I think we’re moving to
a place where, rather than just doing that one test that might be
relevant to one drug, we’d be able to do a test which at the same
price would generate information that could be relevant at
further points in your life if you were requiring different types
of medicine. So, that information would then be available in your
hospital record, in your GP record, that you could have access to
it yourself. And then I think ultimately what we would really
love to get to a point is where everybody across the whole
population just has that information to hand when it’s required,
so that they’re not waiting for the results of a genetic test,
it’s immediately within their healthcare record. That’s what we’d
call pre-emptive pharmacogenetic testing, and I think that’s the
golden land that we want to reach. 


Vivienne: So for instance, I might have it on my NHS app, and
when I go to a doctor and they prescribe something, I show my app
to the GP, or something pops up on the GP’s screen, or maybe it’s
something that pops up on the pharmacist’s screen. 


Bill: I think that’s right. I think that’s what we’re looking to
get to that point. We know that colleagues in the Netherlands
have made some great progress at developing pathways around that.
There’s a lot of public support for that. And pharmacists are
very engaged in that. In the UK, the pharmacists, over the last
few years, have really taken a very active role to really push
forward this area of medicine, and this should be seen as
something that is relevant to all people, and all health
professionals should be engaged with it. 


Vivienne: And on a scale of one to ten, how difficult is it going
to be to implement in the NHS? 


Bill: So, that’s a difficult question. I think the first thing is
identifying what the challenges are. So I have not given you a
number, I’ve turned into a politician, not answered the question.
So, I think what has happened over the last few years, and some
of our work within the NHS Network of Excellence in
pharmacogenetics and some of the other programmes of work that
have been going on, is a really good, honest look at what it is
we need to do to try to achieve pharmacogenetics implementation
and routine use. I don’t think the challenge is going to be
predominantly in the laboratory. I think we’ve got phenomenal
laboratories. I think we’ve got great people doing great genetic
testing. I think the biggest challenges are going to be about how
you present the data, and that data is accessible. And then
ensuring that health professionals really feel that this is
information that isn’t getting in the way of their clinical
practice, but really making a difference and enhancing it, and of
benefit both to the healthcare system but more importantly to the
patients. 


Vivienne: Now, when I hear you both talk, my mind turns to drug
discovery and research, and Matt, I’m quite sure that that’s
right at the top of your mind. Tell us how pharmacogenomics can
help in drug discovery and research. 


Matt: So, pharmacogenomics, I think actually just genetic
profiling of diseases in itself just to start off with is
actually a really good way of identifying new potential
therapeutic targets, and also from derisking drug development
programmes by highlighting likely adverse drug reactions of
medications that are being considered for therapeutic trials, or
targets that are being considered for therapeutic development.
Pharmacogenomics beyond that is actually largely about – well, it
enables drug development programmes by enabling you to target
people who are more likely to respond, and avoid people who are
more likely to have adverse drug reactions. And so that
therapeutic index of the balance between likely efficacy versus
likely toxicity, genetics can really play into that and enable
medications to be used where otherwise they might have
failed. 


This is most apparent I think in the cancer world. A classic
example there, for example, is the development of a class of
medications called EGFR inhibitors, which were developed for lung
cancer, and in the initial cancer trials, actually were
demonstrated to be ineffective, until people trialled them in
East Asia and found that they were effective, and that that turns
out to be because the type of cancers that respond to them are
those that have mutations in the EGFR gene, and that that’s
common in East Asians. We now know that, wherever you are in the
world, whether you’re East Asian or European or whatever, if you
have a lung adenocarcinoma with an EGFR mutation, you’re very
likely to respond to these medications. And so that
pharmacogenomic discovery basically rescued a class of medication
which is now probably the most widely used medication for lung
adenocarcinomas, so a huge beneficial effect. And that example is
repeated across multiple different cancer types, cancer
medication types, and I’m sure in other fields we’ll see that
with expansive new medications coming in for molecularly targeted
therapies in particular. 


Vivienne: So, smaller and more effective trials rather than
larger trials that perhaps seem not to work but actually haven’t
been tailored enough to the patients that are most likely to
benefit. 


Matt: Yeah, well, particularly now that drug development
programmes tend to be very targeted at specific genetic targets,
pharmacogenetics is much more likely to play a role in
identifying patients who are going to respond to those
medications. So, I think many people in the drug development
world would like to see that, for any significant drug
development programme, there’s a proper associated
pharmacogenomic programme to come up with molecular markers
predicting a response. 


Vivienne: We’re going to wrap up there. Thank you so much to our
guests, Bill Newman, Anita Hanson, Matt Brown, and our patient
Jane Burns. Thank you so much for joining us today to discuss
pharmacogenomics in personalised medicine, and the benefits, the
challenges and the future prospects for integrating
pharmacogenomics into healthcare systems. And if you’d like to
hear more podcasts like this, please subscribe to Behind the
Genes. It’s on your favourite podcast app. Thank you so much for
listening. I’ve been your host, Vivienne Parry. This podcast was
edited by Bill Griffin at Ventoux Digital and produced by the
wonderful Naimah. Bye for now.