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This is the second episode of the National MPS Society's Podcast: Our Voices with host, Stephanie Cozine. Join us as we talk to Dr. Emil Kakkis and Ryan Dant about the trials and tribulations of drug development. We share a story of a passionate doctor racing to bring treatment to patients, like Ryan, that will alter the course of those living with MPS I.
We explore the unique lives and work of our community's leaders, professionals, and inspirational members--conversations about the challenges, courage, and dedication that are pillars of this community. We share new perspectives, insights, and knowledge about the rare disease that impacts our daily lives and guides our individual journeys.
The National MPS Society exists to cure, support and advocate for MPS and ML.
Stephanie Cozine: Thank you for
tuning into the national NPS societies
official podcast, our voices.
I'm your host, Stephanie cozy today.
I have the pleasure to share with
you the personal stories of two
incredibly inspiring individuals.
It isn't often that you get
to meet someone who has such a
profound impact on your life.
As many of you know, my son, Ethan was
diagnosed with MPS one further syndrome
when he was nine months old, started in
some replacement therapy shortly after
and had a bone marrow transplant bias.
Navigating the difficulties of a
devastating diagnosis and treatment
searching the internet for whatever I
could find about my son's condition.
One story I came across was
the glimmer of hope I needed.
It was the story of Ryan dance.
Today.
I have the privilege and the honor
to introduce to you Ryan Dant and Dr.
A.
Cactus who led the development and
approval of enzyme replacement therapy.
Aldurazyme a drug that is now the
standard of care for MPS one, a drug
that went through too many obstacles
before becoming the treatment.
So many families in our community
had hoped for and desperately needed.
And his recent book saving Ryan, Dr.
Kakkis passionately Chronicles,
his research and mission to treat
patients with MPS one for which
he is here to share with us today.
Thank you, Ryan and Dr.
Kakkis for joining me.
Dr. Emil Kakkis: Thanks for having us.
Thank you for having us.
Stephanie Cozine: Excellent.
Dr.
Kakkis, let's talk about
your book saving Ryan.
What inspired you to write this book?
Dr. Emil Kakkis: Well, There are
many reasons, but I felt that the
struggle of a family to figure out a
way to save their child and to connect
with a scientist at the beginning
of their career was an important.
Concept for them to think about in
dealing with their own children every
week, thousands of kids get diagnosed
with new rare diseases that many
of which have no treatment at all.
Many parents are in the same position.
Mark Dan was in the book, gives them
an outline of what it could be like
for an average person and family
to get struck by genetic level.
And to fight through the struggle, the
pain, to find a way to be active and
create a solution and save your child.
Stephanie Cozine: Now, there are several
threads throughout your book on, you
had described him to me previously.
Would you mind going over
a couple of them with us?
Dr. Emil Kakkis: The first one, I
just stayed with families finding.
Second one was about biotechnology
and the science that involved
in putting it together and
developing it and what it takes.
So there's some learning that there is,
I think one of the real important thing
relates to the public policy about drug
development and what it takes to get a
rare disease drug approved, or in the
story you learned that in the early days,
the beginning, the FDA played a prominent
role in accelerating the work by giving
us the opportunity to get into the.
And breaking down barriers
and that was so important,
actually getting success at all.
And then we ran into changes at
the FDA and became more difficult,
more cynical, more difficult.
And we ended up losing a lot of time.
And with that delay in time,
we ended up spending a lot
more money and more tragically.
We lost a number of patients who didn't
get treated because of that delay.
And so the book, one of
the important threads.
We need to do better and how we
regulate and manage these treatments.
So the science we have
is reaching patients.
Stephanie Cozine: Now reaching
patients that need it.
That is basically what this
book is centered around.
Delivering drug to the patient,
how you were going to do that.
You take the time to look back at
different moments and individuals
that guided you in some way.
To that moment in that room, giving
the drug to patient for the first
time you mentioned your father his
practice as a physician and the deep
respect you have for the researchers
that paved the way to your work.
You mentioned how enzyme replacement
therapy, wasn't exactly the
bright and shiny science that you
originally had wanted to work with.
And.
If you wouldn't mind sharing with us a
little bit about the influential people in
your life and your career decisions that
ultimately led to this drug development?
Dr. Emil Kakkis: Growing up with my
father who was a neurologist and a very
good neurologist and highly respected.
And I learned at a time when I didn't
think I was going to be a doctor.
About what it takes to be a great doctor
and how sometimes you have to start
things that no one's ever done before.
And sometimes those things
fail and you have to learn
how to support your patients.
Or as I said in the
book, , hold their hand.
When things don't go well, and that
was very important in my thinking,
he also developed a new or worked on
a new treatment for Park's disease.
So I could see how exciting it was.
But at that time, I didn't
know I was going to do.
Rare disease, drug Velma.
I know I was even going to be a doctor,
but those early memories do provide an
imprint on my thinking as I move forward.
Another important threat is my
other side of the story is Dr.
Neufeld, who was a a young woman
scientist in the sixties when she
started working at NIH at a time when
there were very few women and those
that were in fine, she thought were
considered eccentric, but she didn't care.
She.
Hardcore deeply driven by the science
and discovered a way to treat MPS one
in 1968 and spent the next 30 years
working out how to turn that science
into something that could be used.
But her story kind of led
and connected with my story.
I was a fellow and she basically said
to me, we finally have the science
to be able to replace that enzyme.
That MPS one patients are.
And to me as a scientist, thinking
about my career in research, it
was a relatively industrial like
project just to make enzyme.
It wasn't very sexy science.
It was pretty basic.
But what I didn't appreciate
is that the science may not be
fancy, but it's so powerful.
If it can change future the patients
in front of you and that direction,
she sent me on, put me on the
path to be able to develop a true.
I trusted her because we're years
of experience to guide me accepted
that and went wholeheartedly, edit.
And over time I realized
something really important.
Doesn't matter how fancy the
sciences, how cool the journals are.
If you don't help anyone, you
haven't really done anything.
And when you get the chance to
take an enzyme therapy and treat
kids like Ryan for the first time,
You want to do that over and over
again for the rest of your career.
And you realize doesn't matter what
it is, if it can actually change
their future, that's what you want.
That's the measure.
Stephanie Cozine: Now, she was actually in
the room with you with your first patient
receiving enzyme replacement therapy.
Could you explain to us.
What that feeling was like?
Dr. Emil Kakkis: When we finally got
there, I called her up and I told
Liz we're ready to start this trial.
And she said really so early so soon.
And she was a little bit nervous and
I said, look, Liz, we're ready to go.
And I want you to come down
and start the first infusion.
And she was a little bit nervous
that if I press the button,
what if something happens?
Now going to happen, it's going to take
four hours for the infusion and go in.
So it's symbolic.
And honestly, after 30 years of
work, how could he not let her be
in the room and actually treat the
patient for the first, say, 30 years
from figuring out how to treat.
I had to give her that symbolic
moment, come in, start the
first infusion to correct.
As she used to call it
the deficiency in MPS one patient.
That was an amazing moment.
We captured on video and I was so
excited to be able to give her thrill
of her career and seeing senior
science come back to the patient.
That's incredible.
Stephanie Cozine: throughout the
book, it was very obvious in your
writing, how important developing
and guiding your team was.
I appreciate the detail that you gave
about each team member and every person
that contributed to this mission.
It was very humbling, especially
as a parent, I often think about,
who all was involved in creating
this drug that has positively
impacted my son's life and my life.
Reading this and getting to know them, and
then reading about the struggles and the
blows that your team faced over the years.
Could you tell us how you help
keep them motivated and focus?
And one example that comes to
my mind is the picture of ginger
that you placed on the lab door.
Dr. Emil Kakkis: No matter what project
you're doing, it takes more than me.
So I didn't do the thing by myself.
I did, I started it, but it took a
strong dedicate team to make it.
And I learned that early on, talk
about realizing how much I need to find
people that were aligned and directed
to your goal, that they wanted this,
that they wanted as bad as you want.
And there, we're not just taking a
job to get paid, but they're taking a
job to do something with their lives.
And we started building that team,
that dreams, as we're getting
going, for many of them, they
had no connection to patients.
Whereas I had a constant connection to
patients were calling me in waiting.
When is this coming?
And one of those patients had some
chemical problems that had to get surgery
for cord compression named ginger Griffin.
She was a wonderful young woman
with milder disease, but mild
doesn't mean you're not terrible.
She'd had heart valve surgery and
she'd had this terrible problem.
And I convinced her to go get surgery
because I thought the enzyme therapy was
coming and she'd be a great candidate.
She went and got the surgery and then
she died the year before we got to
the clinic and she couldn't make it.
And it brought to home something
that I wanted the team to know.
Is that somewhere right now,
there's someone waiting for you,
someone who may not make it.
If we don't get there, I want them to
have that sense of urgency and importance
on their mind when they enter the lab.
So I took a picture of ginger
Griffin and a little inscription.
I put it on a plaque
right in the front door.
When you go in the labs every
day, gender Griffin's face.
If you forgot you remember what we're
doing and why getting it done really.
Stephanie Cozine: It's powerful
to put the face to the mission
and the heart of that mission.
There was also another part where
you were talking about the urgency
of getting this to patients.
I believe it was over
a Christmas holiday.
And just reminding your team about how
you couldn't put it off any longer, do you
mind telling us a little bit about that?
. Dr. Emil Kakkis: That year,
which was 1997, the team,
which has less than 10 people.
Had been working incredibly hard.
It was a 24, 7, 7 days a week thing
for months and we were tired, but
we're working very hard to get to
the clinic because we wanted to
treat the patient as soon as possible
as it was getting into December.
We were planning to have the first
patient treated actually late in
December the week before Christmas.
And.
The team saw that coming.
And my head of the lab, Becky taught
Amachi was terrific and great at
running lab and holding them together.
By the way, in that stressful year came
to me and said, the team's exhausted.
We need a break.
If you dose them in December, we
won't be able to take Christmas off.
And we really want to take a little time
off because they've done all this work.
I thought about it for
a little bit, a moment.
I said, okay, Becky.
So what you're telling me is you want me
to call up the family that's coming in
for infusion and tell them that they, you
can't come for your first infusion because
the team needs a break until next year.
And she looked at me, as I said that
and said, nevermind and defined and.
A lot of people wonder what was my meat?
Why was I saying that?
I said, I wanted them to
understand this is the truth.
If it sounds bad, maybe
it's cause it is bad.
And that's not to say they
didn't work hard or not to say
that didn't deserve a break.
But right now, at the beginning of
it, the very first patient putting
it off would crush that family,
and disrupt a lot of people.
Fortunately that team held it together
crazy year and a crazy year after that.
But honestly, there was such a great
return when we got to be in the room
in December and see the first kid
treated with all the work that we did.
There was no better moment than that.
Stephanie Cozine: That's awesome.
Ryan you're here today and you were
a patient number three and as I am
reading through all the accounts from
your father and your mother and Dr.
Kakkis, there are a lot of things that
I start to think about and something
that I relate to your family with.
When do.
When will he start to notice that maybe
he's different or that he has NPS?
And so my question for you is, at what
age or what, like timeframe did you
start to notice that you were maybe
different from the other children?
And when did you realize the
severity of your condition?
Ryan Dant: I think, I didn't really notice
I was that different because yes, I was
going to a lot of doctor's appointment
prior to getting the first dose.
And I was getting sent home with
terrible headaches and vomiting and
passing out for the night, but I
just didn't really connect it with my
age group that I was any different.
But then when we went out to UCLA
in 98 for the first trial for my
first dose, that's when I start.
Actually notice that the severity
of it, because I'm thinking I
haven't heard any kids in my class
going to a doctor and having to do
medicine and things of this nature.
But now here I am out at UCLA Harbor
spending a couple of months out
here and I'm getting a medicine.
And I'm thinking, wow, this must be bad
as well as I had to skip a couple of
weeks prior to that, the skip school,
and then get all my schooling done in Los
Angeles at a local grade school there too.
So I had to change all my regular
habits to move everything to
California for the clinical trials.
Stephanie Cozine: And that's
a lot transitionally for
a child at nine years old.
There was a story of where your
father, was laying next to you
in the middle of the night.
And you had a very profound statement
about asking him what death was like, do
you remember that conversation with your.
I
Ryan Dant: remember it a little bit,
because that was probably one of the
days I had a bad headache and I was just
getting tired of having the bad headaches
and I just thought to myself what's next.
So I asked my dad, what was that like
Stephanie Cozine: as a parent?
I don't even that's a tough one.
you were talking about being
out in California and having to
basically pick up your life and
move out there with that transition
and knowing, starting to realize.
That you needed this treatment.
Your family did a great job of
advocating for you and fundraising
and trying to find this treatment.
And here it is, you finally have it.
Did that change your perspective and
outlook on life as a nine year old?
Ryan Dant: I think it did because I
hadn't really noticed any difference,
anything different, like getting
medicine, needing to get medicine.
But once I got the first dose
I was realizing maybe there is
something drastically different.
That I need to do.
And let's see how long
this medicine lasts.
And I remember we had Dr.
Takas and I had a little bit going on
prior to pushing the button that he paid
me $10, that I would feel better soon.
Thankfully, I didn't take that
bet because he would have won it.
Stephanie Cozine: your parents did
an excellent job raising awareness.
And a lot of that, came out in
features like with 60 minutes
and articles and reader.
, even our first guest speaker, Isabel, she
read this article that brought her hope
and she was in Guatemala at the time.
And so this, you were very much in
the public light and in the spotlight,
especially representing our community.
What was it like growing up
and being a public figure?
For.
Ryan Dant: I didn't really notice
that I was a public figure.
And so one time when my family and I went
out to Florida for a family vacation,
we had a random family come up to us and
say, weren't you in such and such article.
I was like, oh wow, we're
all the way in Florida.
And people are talking about our story.
Then later that night we went
to an ice cream shop and we
saw the reader's digest cover.
I was like, holy cow, this is big news.
If this is making it a
lot of away, the Florida.
And that's when I started.
Gravitate or acknowledge that
yes, I am leading the way and
being type of an image for the NPS
community is just amazing to see.
Stephanie Cozine: Absolutely.
Do you feel like that's helped
shaped your life, like being in the
public spotlight for MPS, like your
decision making and all of that?
Ryan Dant: I think it has because when
I was younger, my parents always told
me not to grab it, not let this disease
defeat me, try to live a normal AKA
normal life to the best that I can.
And so that's what I did.
I went to grade school, lived, went
to grade school, got treated as
normal as possible, then went to a
new high school and we were worried
that I'd get treated differently.
But luckily I was treated just like
any normal kid, normal high schooler
just joined the football and baseball
teams there and then do a week the
IB infusion at home and just grab.
Continue to grow up and go through the
normal life of growing up as a teenager.
Now, young adult, I
Stephanie Cozine: know your
parents are very proud.
I'm proud as well.
I think we all can say that.
Obviously one of the biggest milestones
in this journey to save right.
Was being able to get
dropped to the first patient.
And in the first clinical trials, there
was a lot of detail describing the
process from its humble beginnings in the
dingy UCLA lab, and a lot of information
learning about GMP standards and so on.
Dr.
Kakkis what do you think were the
most difficult challenges and the
best lessons learned in your practice?
Dr. Emil Kakkis: We were beginning
in a place that had no experience
and no history of making a
product for human use at all.
So I didn't know anything nor
was the place really appropriate.
We were in world war II, era bungalows
have been there for 50 years and
were worn down and falling apart.
The only advantage of that space
is that I had a lot of space.
So I means I had room.
The biggest learning was that.
It doesn't matter what you want to do.
If you don't learn the practical
details of what are required to
actually produce a drug for human
use, and it's not going to happen.
That means all of the mechanical and
simple things, the pieces that have
to be put together into assembled into
a controlled manufacturing process
to make a product and put it in a
vial that you can give to people.
Was incredibly difficult and gave me
great respect for what it takes to
manufacture biotechnology products
of the quality and care required.
We had to learn a lot about
good manufacturing, practice
rules and regulations, but the
truth was a lot of those rules.
Regulations are very superficial.
The standards are almost unknowing.
And so the other big lesson is you have
to hire people that have experienced
that, know this stuff because.
It's not like it's all
written down on a textbook.
You can look it all up.
Every situation is different.
It requires hiring talent.
With experience.
We're able to get a few people that
had experienced and the rest of us
went to classes and took classes
on how to become GMP compliant
and what a crazy year it was.
But we all learn.
Great people helped us.
And we managed to get it done even
in the dingy old world war II era
bungalow.
Stephanie Cozine: And that was
even before, modern internet and
Googles, search engines and all the
information just available to us.
So I definitely have an appreciation for.
The work then, in my opinion, some of
the most intense chapters in the book
are the ones detailing the ad comm
meeting that eventually recommended
the FDA approval with a 12 zero vote.
And I believe you titled it.
Yes.
For life.
Spoiler alert.
I obviously know that
the drug gets approved.
My son, he has been fortunate enough
to be able to receive Aldurazyme, but
as you detail this meeting, so many
emotions are evoked in me as a parent
and as a reader, listening to the patient
testimonies and just the exchanges with.
One of the most interesting
things I found is that you didn't
mention about conceiving your idea
for the every life foundation.
That was something that I had talked
to you about in a previous interview
leading up to now, which might
telling us a little bit more about
how you conceive that idea and why
you wanted to pursue creating this.
. Dr. Emil Kakkis: I think one of
things you understand as an advisory
committee is where outside experts
are brought in by the FDA to advise
them what came out of that meeting is
the absolute expert said 12 to zero.
The drug was working and the
FDA had said they weren't sure.
And they want us to know that.
The fact that group of X, we could
have such a different opinion,
told you there's a problem, right?
There's a problem with what's
happening at the FDA and how
we're approaching development.
And that problem was that we're taking
good science and we don't understand it.
And therefore we're creating difficulties
that translating into an approved
treatment at that meeting, I realized.
The views we had on this were right.
And the FDA was not right.
And their opinions on biomarkers
on the trial design and other
aspects were not necessarily the
right ones for a rare disease.
And so I decided there that point,
that when I have a chance, I wanted
to open foundation that was going
to focus on improving the process
of drug development, rare diseases.
So that kind of situation to them happen.
So we don't have those
delays that are unnecessary.
That we figure out how to take the
science and get it through the system
and that you have an FDA that wants
to help and collaborate and drive the
quality of what we do hire and assure
that drugs are safe and effective
and that we get it done properly.
And so the foundation's goal was
to take on whatever we had to at a
policy level to change the pathway
and the ability to innovate for rare
disease patients with biotechnology.
Stephanie Cozine: So one of my earliest.
Interactions with the
rare disease community.
After my son's diagnosis was
attending a And advocacy week in DC.
And it was hosted by the, every
life foundation and RD LA.
And it was just such an incredible event.
Getting to meet other rare disease
patients and family members, advocates,
networking with such incredible people
in positions that could really help our
families and just empowering us to be
able to use our voices To provide that
influence with our policy makers and it
was at that trip that actually, getting
to listen to those stories helped me
to develop the idea of developing this
podcast and bringing these voices forward.
So I just want to thank
you for that experience.
And it's something that I'm definitely
going to encourage others to, to seek.
Dr. Emil Kakkis: Yeah, rare disease week
is a great event, but it has two features.
One is to help parent patients, families
see other families in the same, but
the second is to bring you together and
make sure that Congress sees you too,
that you see all of you as a big group,
not just as individual rare disease,
that you're a power is being together.
And to have 600 800 rare disease
assets all going on the Capitol
hill and talking to legislators.
Is an incredibly powerful thing, is
that pulling people together that
gives us the strength to change.
What has to change for
rare disease patients?
Stephanie Cozine: Absolutely.
Some of the most touching yet
heartbreaking stories that are shared
in your book, saving Ryan are in
the epilogue where you give us many
updates on the original trial page.
You don't shy away from revealing
the heartache and the losses that
accompany a disease like MPS.
And I can tell how deeply you care for
each of your patients and their families.
Most of this interview has been centered
around how you've changed so many
lives into this state that is upwards
of 3000 individuals and NPS one alone.
What I would like to ask
you is how interacting with
these patients changed your.
Dr. Emil Kakkis: I think the most
important thing is to start to
realize that science for science
sake doesn't make any sense.
Science in the service of people, real
people, real problems, it's powerful
and what this work did and what meeting
all these families did was allowed me
to find my purpose in life, which was to
develop as many rare disease treatments
as I can to treat as many rare diseases.
And since that time I've been involved
in or had approval for 11 different rare
disease treatments, including Aldurazyme.
And it's been so powerful to
takes other communities and bring
them their first treatment ever.
And that finding that purpose of
what really came through and it came
through not only from saving people,
but even PayPal that you had help in.
Teach you something about life and
the meaning of the struggle that we
are in that the struggle we make as
a scientist, working with a family is
an important part of human endeavor in
feeling what makes us special as people.
And I don't think, I can't imagine
a better field for one to be in then
one where you're helping families
find a way forward and work with.
Sometimes saving them.
Sometimes you're holding their
hand through this incredible
crisis of their lives.
Nothing more powerful than doing that.
Stephanie Cozine: Absolutely.
And I remember the first time that I
met you, which was at the rare disease
week, it was such a humbling experience
to be able to meet the man who had
such an influence and developing a drug
that could help my son have a better.
So it's a wonderful opportunity
to have you here with us
talking about all of this.
Now, Ryan, it's been almost 25
years since your first dose of
Aldurazyme, which has completely
altered the course of your life.
You're in the book, your dad mentioned
that doctors first said, you know
what, take him home and love him.
And until you pass and he just
didn't find that to be acceptable.
So he saw a treatment and with that
treatment, you've now graduated college.
You have a career and you've
recently gotten married.
Congratulations.
What is some advice you would be
giving to the other Ryans out there?
Perhaps younger generation of
effected individuals or other rare
disease communities that are waiting
for that opportunity of treatment?
Ryan Dant: Never give up and
live life to the fullest.
Don't let the disease.
Hold you back from accomplishing
anything, because there will be a cure
for some of these diseases one day.
It just, you never know, you just
got to live life to the fullest,
Stephanie Cozine: And as a parent, I,
a lot of this really sounds cliche, but
like my entire perspective on life changed
when we got this diagnosis and I feel
like I am more capable of living life now.
Just because I know how incredibly
precious it is and the opportunity that
I have with my son now in this moment.
That's definitely some great advice
for, young adults or, maybe teenagers
as they, age into being an adult.
Thank you both very much
for joining me today.
It has been an honor and a privilege to be
able to talk with you about your book, Dr.
Caucus, saving Ryan and Ryan
speaking with you about your
journey with NPS and treatment.
Thank you very much.
Take care.
Again, I am Stephanie, Cozine
your host for this episode of
our voices, the official podcast
of the national MPS society.
I want to thank our guest speakers, Dr.
Amy and Ryan Dan for joining
us today and sharing their
experiences and personal stories.
If you would like to read Dr.
book, saving Ryan, it is available for
digital purchase for Kindle on Amazon.
And if you enjoy the traditional page
Turner, a hard copy will be available.
Thank you to the volunteers and staff
that made this episode possible.
If you want to learn more about NPS or
would like to donate to the national
MPS societies mission, check out
our website@wwwdotmpssociety.org.
Follow us on Facebook,
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Make sure to tune into our latest episodes
dropped on the last Tuesday of each month.
Looking forward to sharing
more of our voices.