(Music)
Hi, my name is Peggy and my son
Christopher was diagnosed at age four
and a half with late infantile Batten
disease.
Late infantile Batten disease
starts to show symptoms around age 3
beginning with seizures, loss of motor
skills, then loss of the ability to walk,
talk, swallow, interact and it is always
fatal.
Because its genetic
sometimes there are
two and three children in the same
family that are all affected, and again it's always fatal.
No child has ever
survived Batten disease.
It is neurodegenerative so there's an enzyme
in everyone's body that allows the brain
to rid the fatty deposits and around the brain cells.
Children with Batten disease
are missing that enzyme, so it's kind
of like having garbage without a garbage
truck.
So it just deteriorates the brain cells as
it progresses and it progresses fast.
Christopher passed away at age eight and
a half for Batten disease.
The vast
majority of rare diseases have no
Fda-approved treatment and so the
treating physicians really have to use
trial and error to try to find something
that works for patients.
Most people think
this is because the markets are so small
and no one is really motivated to
develop drugs for rare diseases but
there are other problems and challenges
that the stakeholders are working on.
And
one of the biggest ones is we really
don't know what happens with people with
rare diseases because in fact they're
uncommon and a physician might only see
one or two in their entire career and so
we don't have a good idea of what's
called the natural history.
In other
words, how do these diseases progress
over time.
FDA, along with multiple other
organizations, is working to remedy this
so that when developers are planning a
treatment for rare disease they'll be
able to plan a clinical trial, they'll
know what happens to people, they'll
understand what outcome measures to
measure or look for in the progression
of the disease.
And this will lay out a better path for developing treatment for any given rare
disease and make it a lot more likely
that an actual treatment will be found.
So
I encourage everyone to work together,
get those natural history studies, those
registries done so we have even more
success in treating rare diseases.
In 2017, the U.S. Food and Drug Administration's Center for Drug Evaluation and Research approved
many new innovative therapies for patients with rare diseases-including the first treatment
for Batten disease, a rare and fatal disorder of the nervous system.
The new FDA-approved drug, Brineura (also known as cerliponase alfa), treats the slow
loss of walking ability in children age 3 and older who have a form of Battens known
as CLN2.
FDA granted the Brineura application Orphan Drug designation (among other designations),
which gives incentives for drug development for rare diseases.
So how did this approval happen-and what are its implications?
There are many complex issues when conducting clinical trials for rare diseases.
The Brineura application is one of the first few applications that used a historical control-that
is comparing study data to natural history data for patients with the same disorder.
This presented challenges.
First, the study data and the data in the historical control had to be comparable.
Second, we had to make sure that rating scales to measure the efficacy endpoint were comparable.
We focused our evaluation of efficacy on walking data because the two studies were not comparable
in the measurement of another efficacy endpoint, language use.
At 96 weeks, there was a statistically significant difference in motor function favoring the
Brineura-treated group.
We've learned a lot reviewing this submission which will be helpful in guiding future rare
disease drug development including addressing complex clinical trial issues.
Many rare diseases affect the central nervous system, causing neurocognitive and neurodevelopmental
problems.
One of the problems of delivering drugs in general, and large molecules in particular,
is crossing the blood-brain barrier.
To deliver a drug to the central nervous system, one must bypass that barrier.
Now that's problematic because this barrier is designed to limit access to brain tissue.
As a pediatrician, I know that some solutions to this problem aren't practical,
especially for children because they're so very active.
So it's not just about developing the right treatment but delivering it effectively.
Brineura is administered into the cerebrospinal fluid by infusion via a specific surgically
implanted reservoir and catheter in the head.
This solution is a first step toward the goal of developing drugs that can be taken up into
the central nervous system.
Brineura isn't right for all patients.
The drug should not be administered to patients if there are signs of acute intraventricular
access device-related complications, such as leakage, device failure, or device-related
infection.
Brineura also should not be used in patients with shunts used to drain extra fluid around
the brain.
The most common adverse reactions in patients treated with Brineura included fever, ECG
abnormalities, hypersensitivity, decreased or increased protein in the fluid of the brain,
vomiting, seizures, and hematoma.