CINCINNATI, OH (Ivanhoe Newswire) - The New England Journal
of Medicine calls it a milestone. Patients who've tried it say it's changed
their lives. Now, there's a new breakthrough in the treatment of a lung disease
that kills patients by their mid-thirties.
Growing up, Angela Riddell loved swimming and softball, but
cystic fibrosis made it hard for her to play.
"[I] couldn't run, [I] was constantly coughing and
couldn't catch my breath," Angela Riddell told Ivanhoe.
Angela's spent most of her life in and out of the hospital,
struggling to survive.
"Rough, it's been real rough," Angela said.
Cystic fibrosis is caused by a genetic abnormality. It
results in thick, sticky mucus building up in the lungs and digestive tract
leading to life-threatening infections and difficulty maintaining weight.
"Patients are dying right in the prime of their lives,"
JP Clancy, M.D., a professor and director of CF and clinical and translational
research at Cincinnati Children's Hospital Medical Center, explained.
Doctor Clancy believes a new oral drug could change that.
VX770 targets one of the genetic mutations that leads to CF and reverses it.
"It's really unprecedented and many people consider it
a game changer," Dr. Clancy said.
In a phase 3 clinical trial, adult participants taking the
drug gained an average 10.6 percent more lung function after 24 weeks and put
on seven pounds. Children increased lung capacity by 12.5 percent and gained
eight pounds.
It has put Angela back in the game. Before the drug, her
lung capacity was at 48 percent and now it's shot up 23 points to 71 percent and
she's also gained 20 pounds.
"I can see my future and it's getting older and seeing
grandbabies," Angela said.
Neither kids nor adults in the study experienced side
effects that were clearly related to the new medicine. It's important to note
the drug only targets one of the genetic defects that leads to CF. The FDA is
expected to approve VX770 early this year.
Additional clinical trials are underway targeting some of
the other common mutations that cause the condition.
RESEARCH SUMMARY
BACKGROUND: Cystic fibrosis (CF) is an inherited chronic disease that
affects the lungs and digestive system of about 70,000 adults and children
across the globe; at least 30,000 of those affected with the disease can be
found in the United States. A defective gene and its protein cause the body to
produce unusually thick, sticky mucus that clogs the lungs and leads to
life-threatening lung infections; and obstructs the pancreas and stops natural
enzymes from helping the body break down and absorb food. Cystic fibrosis not
only affects one's breathing and digestive, but people with cystic fibrosis can
also have problems with growth and development. There is no cure for cystic
fibrosis and the disease generally gets worse over time.
SOURCE: (www.cff.org);
(www.webmd.com)
INSIDE SCOOP: 1 in 29 Caucasian Americans have the CF gene. The disease
is the most common, deadly, inherited disorder affecting Caucasians in the
United States. It's more common among those of Northern or Central European
descent. About 1,000 new cases of cystic fibrosis are diagnosed every year; and
more than 70 percent of patients are diagnosed by the age of two. The life
expectancy for people with cystic fibrosis has been steadily increasing over the
past 40 years. In the 1950s, most children diagnosed with the disease did not
make it to elementary age. Now people with cystic fibrosis live into
their mid-to-late 30s, although new treatments are making it possible for some
people to live into their 40s and longer.
SOURCE: (www.webmd.com);
(www.ncbi.nlm.nih.gov/pubmedhealth);
(www.cff.org)
SYMPTOMS: Symptoms for cystic fibrosis differ from person to person;
however, people with the disease are often diagnosed at an early age – mostly
by age two—however in rare cases some people are not diagnosed until age 18 or
older. These patients usually have a milder form of the disease. Some common
symptoms an infant may display are: a blocked small intestine at birth, this
prevents the baby from passing their first stool; salty sweat or skin;
diarrhea, and breathing problems. The baby may not be growing or gaining weight
at the same rate as other infants their same age. The child may also
experience nausea; a loss of appetite; and breathing problems.
SOURCE: (www.webmd.com);
(www.ncbi.nlm.nih.gov/pubmedhealth)
LATEST BREAKTHROUGH: A new drug created by Vertex Pharmaceuticals called VX-770
is designed to treat the underlying cause of cystic fibrosis. VX-770 allows
proteins to function correctly, improving the flow of salt and fluids in and
out of the cell. Patients who took the drug, showed marked improvements in lung
function and other key indicators of the disease, including sweat chloride
levels, likelihood of pulmonary exacerbations and body weight. So far, the drug
shows no side effects.
SOURCE: (www.cff.org)
INTERVIEW
Dr. John Clancy, Professor and
Director of CF Clinical Translational Research at Cincinnati Childrens Hospital
and Medical Center. Discusses a new medication for Cystic Fibrosis patients
with a particular gene that is showing some promise.
Can you give us
the basics on Cystic Fibrosis?
Dr. Clancy: Cystic Fibrosis is a common problem,
and is the most common inherited lung disease that causes a shortened lifespan
in the Caucasian population. About one in three thousand kids in the US are
born with CF. And the problem with CF has to do with a gene that doesn't work
correctly. When that gene doesn't work it causes problems with how salt moves
in different parts of the body. And when salt doesn't move correctly in the
lungs and airway tubes it causes mucus to build up and is prone to infections.
And over time it damages the lungs and leads to shortened lifespan.
What are some
of the symptoms?
Dr. Clancy: Patients with CF have a lot of trouble
with cough, recurrent infections, hard breathing, and in addition they can have
symptoms in different parts of their body. They have problems with growth,
stomach aches, sinus symptoms, problems with dehydration, and a variety of
other things. All of those places where we find symptoms are where this CF gene
isn't working correctly.
You said it's
just in Caucasians?
Dr. Clancy: The most common population includes
people with a Caucasian background. It is being found much more frequently in
Hispanic and African/American populations, but with less than half as many
patients between those two groups compared to Caucasians though.
So Cystic
Fibrosis obviously leads to death?
Dr. Clancy: Over time it causes lung injury and
damage that eventually the body is not able to heal. The average life
expectancy of CF patients is currently the mid to late thirties. There have
been great improvements over the last two to three decades but still patients
are dying right in the prime of their lives.
Tell us where
this new medication comes in.
Dr. Clancy: This is very exciting. It's name
is VX770 and it is a medicine that is taken by mouth and it helps treat the
underlying cause of CF, by opening up the salt transport pathway that doesn't
work correctly in CF. And when that is activated it allows the salt to move
normally, helps the mucus to be cleared from the lungs and really helps to
improve lung function, how patients feel, how they gain weight and how many day
to day symptoms they have. There have been three studies with VX770 over the
last two to three years which have been conducted and they have all shown
dramatic improvements in lung function, weight gain, reductions in symptoms,
and in general patients feel so much better when they're on the medicine.
But it's not a
cure?
Dr. Clancy: It's not a cure, though I wish I could
say that it was. CF patients who take VX770 still have CF. The improvements are
dramatic, however, and they are really exciting because they target the root
cause of CF. However, we still believe that patients, particularly those who
have had some injury to their lungs over time from having CF are still going to
need therapies to help remain well. But we're very excited about the fact that there's
a great clinical improvement and it's really unprecedented. Many people
consider it a game changer in terms of how we may be able to care for patients
in the future.
The patient I'm
going to talk with today will be thirty one.
Dr. Clancy: She's had some amazing responses, her
lung function has improved by approximately twenty five points, her weight has
gone up about twenty pounds and her symptoms are vastly improved compared to
before she was on medicine. VX770 is really exciting and I wish I could say
it's available for all CF patients today or was going to be an immediate
treatment for all CF patients. It really targets one way in which the CF gene
is broken and we hope it's going to be valuable to a lot of CF patients, but at
this point it really just applies to patients who have a certain type of
CF-causing mutation.
So are those
mutations endless?
Dr. Clancy: There are about fifteen hundred
mutations that cause CF and there are all sorts of variations in the way that
mutations in the gene cause the symptoms. Thankfully they can be grouped into
common causes, and those different groups can be targeted for new medicines in
a similar kind of way.
So this
medicine only targets one particular change?
Dr. Clancy: Correct, it targets one of the ways in which
the CF gene and protein is not working. We think it may be valuable to apply on
top of other medications eventually, so it may end up over the long haul being
able to be used in many more CF patients. But right now we only have data on
patients with a certain single type of mutation.
This is a phase
III trial?
Dr. Clancy: This is a phase III trial, there was
one that included patients above the age of twelve, and then its follow up
study (which wasn't as big) included patients who were between the age of six
and eleven. But both of them showed pretty dramatic improvements in all the
different ways that CF can be measured.
What could a
typical patient taking this medication expect?
Dr. Clancy: The average improvement in lung
function was more than ten points and it was very sustained all throughout the
study. The study was a one year long double blind placebo controlled study, so
it was well done from a scientific standpoint. And there was definitely a rapid
and sustained improvement in lung function, and a more gradual but steady
improvement in weight. And another important factor we measure is how stable
symptoms are. The number of symptoms that patients reported were essentially
cut in half. And that's pretty exciting for the day to day life of a CF patient.
And points is
that the same as percent?
Dr. Clancy: Exactly, we measure a percent of lung
function based on how tall you are and how old you are and these improvements
were by percentage points.
If you improve
your lung capacity by ten percent what does that really mean for the patient?
Dr. Clancy: Like all medicines there's a range of
responses, there are the big responders and the small responders. But with an
average improvement of ten points most of us in the field feel it's something
that people would feel every day. You know they would have more stamina, more
ability to go up and down stairs, take care of their home, go play with their
kids, participate in sports, be part of regular activities. And that was sort
of reinforced by the fact that patients had a lot less symptoms, meaning less
cough, felt better, and in general their breathing was easier. A variety of
different kinds of measurements, in addition to just these lung function points
were better. Patients actually felt better, and that's the most important
thing.
On the patient
we're going to see today she was pretty dramatic the, twenty five points.
Dr. Clancy: She really has been, and obviously not
every patient responds in that fashion, but her response was pretty exciting.
She really is pretty inspirational.
What's her
prognoses would you say now that she was able to increase her lung capacity
because before you said mid thirties is what a lot of these people are looking
at.
Dr. Clancy: I wish I could tell you for sure, but
I'm a lot more optimistic about the future when I can see a patient's lung
function jump up by twenty five points. There are t really no therapies that
have that kind of effect that are in use today. So I'd say that the future is
bright, and although hard to predict I foresee a really bright future, there's
a good chance that her CF lung disease will be completely different than it
would have been otherwise.
But it's hard
to say how many years it would add?
Dr. Clancy: We don't know that yet. Unfortunately
these medications have only been studied for about two years in individual
patients. So obviously we're very encouraged, but it's going to take time to be
able to draw the conclusion that what we see over two years translates into
twenty. We just don't know.
You said this
was a game changer, would you say this is probably the biggest breakthrough in
Cystic Fibrosis in a while?
Dr. Clancy: I personally would say that. There
have been a lot of improvements and exciting new approaches to treatments.
Different types of antibiotics, different ways to give them, different types of
medications to treat inflammation and to clear mucus, but this really gets at
the root cause of CF. And it's really very personalized medicine. One of our
goals is to be able to match medicines to patients. And this is really matching
a specific drug to a specific CF-causing mutation, and having it turn around
and really reverse a number of the symptoms that come with it.
You said
basically this was for one specific mutation so I would imagine that mutation
affects a pretty big population of Cystic Fibrosis patients?
Dr. Clancy: There are a number of groups of
mutations that sort of behave the same. VX770 is one that basically opens the
CFTR protein, which is a pathway or a channel for chloride or salt to move
through cells. And as long as the mutant CFTR is at the cell membrane and the
reason it's closed is that it doesn't listen to the right signals on the inside
of the cell, this medicine in theory should open it up. That particular cause
of CF is not very common. It's about five to ten percent of patients that have
mutations that act like that. The most common cause of CF is one called F508
and that's where the problem is that the CFTR protein (which is the product of the
gene) gets stuck inside the cell and doesn't get to the cell membrane where it
can be opened. VX770 targets the second most common cause of CF, and the name
of this mutation is called G551D. It's basically a CFTR protein that gets up to
the cell membrane and won't open, it's just locked closed. And what VX770 does
is comes along and open it to allow salt to go through, which helps water move
correctly. The most common cause of CF is called DeltaF508 and that's a problem
where the protein gets stuck inside the cell and doesn't ever get to the cell
membrane. So it's not available for a drug like VX770 which needs the protein
to be at the cell membrane. So Vertex has developed additional drugs that are
being developed that actually help make DeltaF508 get to the cell membrane. And
one of the studies that's going on now is to take one medicine to help get it
to the cell membrane, and also take a second medicine to help open it up. And
that's the combination therapy that we hope will be available for the majority
of CF patients. That approach is really going to be valuable to up to ninety
percent of CF patients.
Anything else
you would like to add?
Dr. Clancy: I just think it's a really exciting
time, and I think people need to know that this is a very novel way to try to
treat CF. We're not trying to treat downstream symptoms, we're trying to treat
the root cause of CF. The types of responses that we've had with VX770 are
really unprecedented and give us confidence that this approach could really
work to change the face of CF care.
You were saying
this was exciting?
Dr. Clancy: It's a really exciting time for CF
research. It's a brand new and very novel approach trying to help treat the
root cause of CF compared with all of the other current treatments which really
treat downstream problems that result from problems with the CF gene and
protein. The findings we have had with VX770 make us think that indeed this is
a realistic approach and we are very encouraged regarding additional drugs that
are coming down the pipeline. We think that these new strategies will target
additional causes of CF and hopefully be available to the vast majority of CF
patients.
FOR MORE INFORMATION, PLEASE CONTACT:
Jim Feuer
Media Relations Manager
Cincinnati Children's
Jim.Feuer@cchmc.org
