Drug treatment Omegaven that could save infants' lives not yet approved by FDA
Dr. Mark Puder of Boston
Children's Hospital developed
a treatment with a drug made
with fish oil called Omegaven
that he's been using to help
reverse fatal liver disease in
infants. Despite the drug's
effectiveness, it has yet to be
approved by the Food and
Drug Administration. Puder
says that the FDA has told
him they want the usual
rigorous controlled study
where half the patients get
the experimental drug and the
other half does not. Puder
refuses to do the randomized
drug trial because it would
mean that some infants may
die. Dr. Nancy Snyderman
reports.
By Sarah Koch, Deirdre Cohen
and Linda Carroll, NBC News
When an Appleton, Wis., infant
developed fatal liver disease, his
family conducted and exhaustive
search for a cure, and found a
life-saving experimental
treatment developed by Dr.
Mark Puder of Boston Children's
Hospital. Other babies with fatal
liver disease, however, may not
be so lucky because the
treatment isn't currently
approved by the Federal Drug
Administration.
When Sam O'Connor was born in
March of 2008, he was a little
small, just over 5 pounds, but
seemed healthy otherwise.
Within days, however, he
became severely ill, dehydrated
and lost nearly 2 pounds, even
though he was eating well.
When his frightened parents,
Debra and Jason O'Connor took
him to the doctor, they were
urged "to just put him back in
the car and go straight to the
hospital," Jason told NBC's chief
medical editor Dr. Nancy
Snyderman.It took months - and an
intestinal biopsy - before
doctors at the hospital in
Milwaukee figured out Sam had
inherited an extremely rare
genetic condition called
Microvillus Inclusion Disease.
Children born with the disease
can't absorb fluid and nutrients
normally; the only treatment is a
food substitute called total
parenteral nutrition, or TPN,
injected directly into the veins.
While TPN keeps kids hydrated
and fed, long-term use can
cause liver damage. That's what
happened to Sam. The TPN that
was keeping him alive was
destroying his liver - and killing
him.
As the boy's condition
deteriorated, doctors told the
O'Connors that "there was
nothing more they could do,"
Jason said. "We should take him
home. We should make him
comfortable and enjoy whatever
time we would have. They said
he would never live to be 2 years
old," Jason added.
Through an exhaustive search,
the couple discovered an
experimental treatment for liver
damage from TPN used by a
doctor at Boston Children's
Hospital.
The potentially life-saving
medication Omegaven, an
intravenous mixture made with
fish oil, reduces the fatal fat
accumulation in children's livers
caused by TPN. Fish oil contains
anti-inflammatory omega-3 fatty
acids, which have been shown to
prevent fat buildup.It is unclear when or whether
Omegaven will be approved. The
normal FDA process for approval
is to test medications in large
trials that randomly assign
patients to receive either the
new drug or a placebo. In fatal
illnesses, that can present
doctors with a tough ethical
quandary: Do you do the science
right and potentially lose some
patients or just keep treating
patients in research studies
Not daunted by the lack of FDA
approval, Sam's family signed
him up for a Boston Children's
Hospital research study looking
at the new medication's efficacy.
It didn't take long to see results.
"For me, it was . . . the
personality change," Debra said.
"To have him start responding to
me and playing, it's just like he's
actually a person again. You
know, it's almost like his life
started at that point because
before it was just enduring."
Now 5, Sam is one of the lucky
ones because he was able to get
the drug he needed. Other
children aren't so lucky, says
Puder, who developed the
Omegaven treatment after
watching up to four children die
from liver failure each year at
his hospital alone.
Without FDA approval,
Omegaven is available only to
those who can come to Boston
to take the drug in a research
protocol, or at another hospital
with special dispensation from
the FDA, a provision called
"compassionate use."
Knowing that the babies who
need Omegaven could die
without it, Puder refuses to
conduct an FDA trial.
"The problem with the
randomized, controlled trial is
they say to take 50 babies all
with this liver disease and treat
only half of them, when I know
what our results are." Puder
said. "And, honestly, telling a
mother to do that for science is,
to me, unacceptable."
"It's beautiful science," Puder
said, but, he added, "it's bad
medicine."
The FDA wouldn't talk to NBC
News because the agency is not
allowed to discuss any drug
applications for approval. But
Dr. Timothy Cote, former
director of the FDA's division for
drugs that treat rare or so-called
orphan diseases, explained the
FDA's policies in general.
"They want to see real data,"
Cote told Snyderman. "They
don't want to hear your belief.
They don't want to hear how you
feel about the drug. They want
to see facts."
Cote says this is a process for
patients who will die without a
medication. It's called
"compassionate use," and
requires doctors to get special
approval from the FDA on behalf
of their patients.
"That's exactly what
compassionate use is for," Cote
said. "When you have a fatal
disease and you think something
might work. We're not having
babies die because the FDA
won't let the drug to, OK?"
Compassionate use is how Puder
and doctors at some other
hospitals, such as Texas
Children's, are providing
Omegaven for sick babies. But
doctors argue that the
application process is difficult
and wastes precious time.
"The problem with this disease is
it's so rapidly progressive that
you may lose the time to be able
to rescue them," Puder said. "So,
if their liver disease is bad at
two months, and then it's at four
months now, now you've hit a
point where there's a point of no
return."
And even if a child gets approval
for Omegaven and is doing well
on it, there can be problems
continuing the treatment
because it's illegal to ship non-
FDA approved medications
across state lines.
For the O'Connors, that's meant
traveling to Boston every eight
weeks to get Sam a checkup and
to pick up the next two month's
supply of the drug. It's an
expense the family can ill afford.
They've had to borrow money,
raise funds, and rely on the
kindness of people in their
community.
Jason O'Connor's message to the
FDA: "I would like some real
answers on why this process
takes so long."
In the meantime, Puder
continues to submit his data to
the FDA in the hope that the
agency will approve Omegaven
so it can become more readily
available.
