- Dr. Segal gave a nice segue into this talk.
As he has already alluded to,
I have an interest in clinical trials.
I'm focusing on taking what's been discovered
in the laboratory to human beings for some new MS treatment
so I'm going to spend some time
talking about some of that today.
What I'd like to do first is talk a little bit
about sort of where we were before a few years ago
and kind of where we are now and where we're going.
And a little bit about just a brief timeline
and the history of MS treatments
so we can kind of see how things have been evolving
over the last few years.
And I hope that this will convince you
that this is actually a very promising time
for MS treatments.
I also am going to spend a little bit of time
talking about clinical trials and reviewing those concepts
and exactly what a clinical trial is.
And to try to hopefully drive home how important
clinical trials are in terms of evaluating drugs
and ultimately finding and discovering
the best treatments for MS patients.
I think a lot of times people hear about clinical trials,
and they don't really understand necessarily
what that process is.
So I'm hoping I can shed some light on that for you today.
Then I'm going to talk
about a couple of recently approved MS treatments.
Two treatments in particular: fingolimod or Gilenya,
which is a new disease modifying therapy,
and also a medication for symptoms called Ampyra.
And then I'm going to talk about a few new treatments
that are in the pipeline and on the horizon
currently being tested in clinical trials.
But treatments that we think are most likely
to be approved soon.
There's a lot of treatments out there,
and I'm going to keep this talk relatively focused.
But I would encourage you in terms of other treatments,
if you have questions about other treatments
that weren't mentioned in the talk
certainly those questions can be submitted in writing.
So this is just to kind of give you a sense
of where things were and where things are going.
I wish I could've made this timeline longer.
If I had about three more screens
to take you back even into the 1960s,
you could see that things were relatively sparse
in terms of things we had to offer
our MS patients in the past.
If you look at the slide here,
even in the 1980s, in the pre 1980s,
we really only had a few treatments.
Steroids were used to treat patients with MS.
And there was another medication called ACTH,
or adrenocorticotropin hormone.
Some of you who have had MS for many years
may recognize this as a treatment that helps your body
stimulate its own steroid production.
And a few chemotherapies including Cytoxan.
But really, that was the extent of the MS treatments
back before 1980.
And it wasn't until the 1990s
when we started to see therapies
that were more specifically targeted for multiple sclerosis.
Betaseron came out in 1993,
that was the first of the drugs.
One of the interferons as many of you may know.
And then eventually, Avonex, Rebif, and Copaxone
all came out sort of in rapid succession
between 1993 to 2001.
And since that time
we've seen more promising treatments become available.
Tysabri, and there a few other chemotherapies here,
one's called Novantrone.
But as you can see that really it's been a boom
since the early 1990s, and it's going to continue to grow.
Because there are many, many new treatments
coming down the pipeline.
So every one of these red arrows here
along this timeline are things
that have already been approved by the FDA.
But this blue arrow just reflects all the other medications
that are currently being evaluated right now
for multiple sclerosis.
So obviously as you can see,
it's actually quite reassuring to see
that so many new medications are being tested
and evaluated at this point.
But what else has changed?
Well Dr. Segal kind of alluded to this as well.
That the timeliness of the diagnosis is improving
with the advent of MRI.
But also the effectiveness of treatments.
So in addition to having more options for our patients,
the new treatments that are being evaluated
are much more effective.
More powerful and efficient methods
of evaluating these drugs is also very important.
And doing our best to get these drugs evaluated
in a timely basis so that they can be available for patients
if they turn out to be effective.
And this is where I'm going to talk a little bit about
the importance of clinical trials.
So what is a clinical trial?
Well, a clinical trial is a study or an experiment
that compares the effect of an intervention.
So this intervention can be a new medication,
a new method of performing a procedure,
a new medical device,
but ultimately something new
that is hopefully going to be used in patients,
and testing it against some sort of a control,
or a comparator. Something where a new medication
if you're going test it, you want to test it
against something that's already available,
such as a medication that's already on the market.
Or in some cases a placebo.
But you're comparing it to another substance
and what you're doing is you're testing
its effectiveness in a particular disease.
And this is a study of humans.
Clinical trials do not involve animals.
When we talk about clinical trials,
we're talking about human studies.
This is the preferred method for the evaluation
of medical treatments and procedures.
And even though this may seem somewhat obvious,
it hasn't been until the last few decades
that this has been more of the standard way
of doctors applying their medical knowledge
and using treatments in patients.
It wasn't that long ago when doctors
would primarily rely on their own experience
or even recommendations from mentors and things like that
to decide which treatment was most appropriate
for their patients.
But with clinical trials, we have much better
and much more objective evidence
that medications do work in patients
and just how effective they can be.
It also helps to evaluate drug safety.
And so this is very important as well
when you're trying to make decisions
about the risks and benefits of a treatment.
And this will give you the best method for evaluating
whether or not a drug is appropriate for each patient.
The purpose of this is to maximize safety
and also to eliminate biases that all of us humans have
when we're evaluating medications.
And so clinical trials are done
in the most objective measure possible.
So you probably, when you're reading about MS medications,
a lot of times you'll see reports
that say a Phase II trial showed this.
Or a Phase III trial showed this,
and what does that exactly mean.
Well clinical trials are broken up into phases actually.
This is something, it's a very systematic process.
So it goes through a very, very well-planned out scheme
for a drug to make it from the laboratory bench
to the patient.
We have what we call the Pre-clinical Phase,
and this is actually the phase
when you're evaluating a drug at the laboratory bench.
And so this means testing the drug on a line of cells
or in animals, to see if the drug has any benefit.
But ultimately this has to be moved on to the humans,
to test it in human people.
In humans, I'm sorry.
So the first step of this is what we call
the Phase I clinical trial.
And the Phase I trial is actually
just the first step in human research.
And what this means is
that this medication is now being taken to human beings,
but it's primarily for the purposes of focusing on safety,
to make sure that this drug is safe for patients.
And this is the one time when a lot of times
the drug is actually tested on healthy people first,
people who don't have the disease.
So this is really just the first step.
It's usually only done in a very small number of people
to find out if it's safe,
and also to find out what the safest dose is.
If the drug passes the Phase I clinical trials
and ultimately looks like it's a safe drug,
and we find a well-tolerated dose,
then the drug will go on to be studied
in what we call Phase II clinical trials.
And this is usually a bigger number of people,
usually within one to two hundred people.
And this is the first study now, this is the first step
in deciding "Is this particular drug active
for the disease that we're using it for?"
So at this point, we're using patients.
We're using people with the disease that we're studying
as opposed to healthy people.
And this is usually what we call a proof of concept study
which means we want to see if this drug is working
in the disease we're studying it in.
Even if we're successful however
and the Phase II studies look good,
and it looks like the drug is effective in patients
who have the disease, there is one more step.
It's called the Phase III study.
And this is a larger study.
It's more confirmatory that what we saw
in the Phase II study is actually true.
We look at the efficacy of the drug
in a larger group of patients at this point.
Usually even as many as one to two thousand people.
And the purpose of the Phase III study
is not only to confirm that the drug works,
but also to gather more safety data.
In larger groups of people,
you can see more safety outcomes.
So it's really important to make sure
you're applying this to a larger number of patients
to make sure that this drug is safe.
And oftentimes this, even though in previous years
this has often been tested against a placebo
or an inactive drug or an inactive substance,
we're moving to an era now where the new drugs
that we're studying are being tested against something
that's already out there on the market.
It's standard care.
So this, we're much more in favor of this
because we do feel for ethical reasons
that patients who are enrolled in a clinical trial
should be receiving some sort of treatment.
And also it helps to know, head-to-head,
how does the new drug stack up against the medications
that are already out there on the market.
So usually this is the last step prior
to a drug receiving FDA approval,
and I'll talk a little about that later.
But just to give you a sense of how things move,
and when you hear these phases, this is what this means.
There are also Phase IV studies.
Oftentimes after a drug becomes approved,
it's still being studied,
even after it's been approved by the FDA.
And companies will continue to gather longterm safety data
and efficacy data on the drugs.
They may be thinking about using it for other indications.
But really the Phase II and Phase III studies
are the ones that I'm going to focus on,
which is why they're highlighted here.
So this is just kind of a neat a depiction.
It's a timeline showing you exactly just what happens
and how a compound makes it from the bench
to the bedside.
So this is your timeline down here
and how long each one of these steps takes.
So for every one drug that gets approved by the FDA,
and anywhere from five thousand to ten thousand
compounds are studied.
So this is not for the weak-hearted.
This is a very competitive area.
But what we see is that it takes three to six years
to study these compounds initially at the bench
or in the laboratory.
But eventually, some of those drugs will look promising,
at least in pre-clinical studies.
And if they're fortunate enough
to look promising in the pre-clinical studies,
they go on to the Phase I clinical trials
like we talked about.
So maybe checking in and testing the safety
in about ten or twenty subjects.
Usually healthy people.
And then ultimately if it passes muster,
it moves on to Phase II and Phase III.
And then eventually, you know if things continue
to look very promising, FDA approval.
And on average the process takes about twelve years.
But this just gives you a sense of where things go.
And then again, more Phase IV studies
to keep monitoring patients for safety.
So on to some of these medications.
So fingolimod, I'm sure many of you
have either read about fingolimod
or have already been talking about it with your doctors.
The brand name for this medication is called Gilenya.
This is the first FDA approved oral treatment
for multiple sclerosis.
It's been almost a year already
since it's been out on the market.
It was approved September 21st of last year.
It is indicated for relapsing-remitting MS.
FDA approved for relapsing-remitting multiple sclerosis.
And this drug works in kind of a unique way.
It actually traps some of the immune cells
that are implicated in multiple sclerosis.
It traps them in the lymph nodes
so that they can't escape into the blood stream
and get into your nervous system to cause damage.
So it's a unique mechanism,
and it's fairly convenient dosing.
It's one capsule, taken daily.
There's only one dose. It's 0.5 milligrams per day.
Another dose was studied in the clinical trials,
and I'll tell you a little bit about that.
But ultimately it was found that
there was no extra benefit in using the higher dose.
And so for safety reasons, only the lower dose has been.