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 About 30 percent of people in the U.S. now suffer from fatty liver
diseases, such as NASH (nonalcoholic steatohepatitis), fueled by
obesity, diabetes and over-indulgent lifestyles, according to the
American Liver Foundation. Without treatment, sufferers can develop
advanced damage, including the scarring known as fibrosis;
cirrhosis, which destroys liver function; and even cancer.
For now, testing patients in trials of experimental medicines
involves a liver biopsy, a painful, expensive and potentially risky
test. Its accuracy is also limited as it draws just a tiny piece of
the liver, which may not be affected uniformly by disease.
"It's a pretty nasty test involving a needle five inches long you
plunge blindly into a patient's side," said Dr. Scott Friedman, dean
of therapeutic discovery at Mt. Sinai Hospital in New York and one
of the world's top liver disease experts. "We don't like to do them.
You can't do more than one at the beginning, one at the end (of a
trial). So there's this frantic effort now to develop (diagnostics)
that will give us the information necessary to know if a drug is
working."
More than a dozen drugmakers are working on new treatments for fatty
liver disease. Frontrunners include Gilead Sciences Inc, a leader in
the hepatitis C field, Intercept Pharmaceuticals and France's Genfit.
If approved, each of their drugs could reap sales of $10 billion
annually, Reuters reported last year.
They will find eager partners in several small companies, such as
KineMed and Perspectum Diagnostics, often spawned from academic or
hospital research, which are working on alternatives to liver
biopsy.
Some of the new techniques use MRI scans that view the entire liver.
Others involve blood tests to measure liver scarring or function.
One diagnostic evaluates liver damage via exhaled breath. They could
replace biopsy or be used to provide interim results during lengthy
studies.
U.S. health regulators "recognize that biopsy is an inadequate way
to power trials," Friedman said. "We can't get interim data about
efficacy."
The U.S. Food and Drug Administration declined to discuss tests in
development. The agency "supports innovation, especially where new
tests and diagnostic procedures might eliminate or decrease the need
for an invasive procedure such as a liver biopsy," a spokesman said.
CONTROLLING COSTS
New diagnostics will also help U.S. health insurers determine which
patients are most in need of treatment to keep a closer watch on
cost. Gilead's hepatitis C cure Sovaldi racked up $10.3 billion in
its first year on the market, prompting a campaign by U.S. payers to
reduce the cost of new medications.
"Who is at risk for progressing to serious liver disease? That's a
giant question," said Marc Hellerstein, president and chief
scientific officer of KineMed and a professor of nutritional science
and toxicology at the University of California, Berkeley. "We cannot
possibly treat 60 million people for a new disease with expensive
new medicines.”
KineMed's test has a patient drink a small amount of water with the
non-radioactive hydrogen molecule, deuterium, which accumulates in
new collagen, the main component of fibrotic scarring. Using a
highly sensitive mass spectrometer, KineMed can distinguish in a
small blood sample how much collagen is being made. The information
could tell companies whether a drug is working in a month versus
years.
"If you've reduced the scar formation rate by 50 percent, then you
know that in a year or two that's going to add up," Hellerstein
said.
KineMed, which is eyeing going public perhaps late this year or
early 2016, is in talks with several drugmakers on using its test in
clinical trials, Hellerstein said.
Collagen Medical, which was spun out of research at Boston's
Massachusetts General Hospital, has developed a contrast agent that
binds to collagen and uses MRI to provide a 3D image of the whole
liver.
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"If you have liver fibrosis then that part of the liver becomes very
bright in the MRI scan," said company co-founder Peter Caravan,
director of the Institute for Innovation and Imaging at Mass
General. The company expects to begin testing on humans for both
liver and cardiac fibrosis with help from grants from the National
Institutes of Health.
Perspectum Diagnostics, started by Oxford University researchers,
has another MRI-based test that won U.K. approval last year.
Chief Executive Rajarshi Banerjee said he was stunned by the
prevalence of liver disease he found during a medical rotation in
the Channel Islands off the coast of Normandy, France, which have a
reputation as a tax haven for the rich.
"You had very wealthy women presenting in their 50s with end-stage
liver disease," he said. "You don't expect that in the U.K.
equivalent of the Hamptons."
His company's Liver MultiScan takes about 15 minutes and offers
easy-to-read full liver images that measure inflammation, fibrosis
and iron build-up, producing a score that can determine need for
medical intervention. It could also help select patients for
clinical trials depending on whether a drug is targeting
inflammation or fibrosis.
He shared with Reuters an image of the liver of a 12-year-old boy
with a 41-inch waist whose advanced NASH was obvious even to an
untrained eye, with large areas of the liver showing dense fat
deposits.
"The chances of this boy reaching pensionable age are minuscule
unless we do something about it," Banerjee said. "It's a sad
indictment of the way we live."
Raptor Pharmaceuticals is testing a drug in children whose NASH was
confirmed through biopsy. Having non-invasive tests or biomarkers
that can prove a drug works would be "a giant leap forward for the
field," Raptor CEO Julie Anne Smith said.
Aurora, Colorado-based HepQuant has discussed using its blood test
with Gilead and others, said company founder Greg Everson, who's
also director of hepatology at the medical school at the University
of Colorado, Denver. Patients either drink or are injected with a
liquid that contains a non-radioactive molecule. A series of blood
tests over 90 minutes measures how it is cleared by the body,
providing information on liver function and physiology.
"We found that the test had tremendous sensitivity over the full
range of liver disease, not just at late stage," Everson said.
"We're hoping we can work with the FDA to set a pathway that's not
too onerous and get this available quickly."
The idea of a breath test for liver function has been around for
decades, but Israeli-based Exalenz Bioscience Ltd may be the first
to bring one to market.
A patient drinks a small amount of water containing a non
therapeutic drug that interacts with the liver. Breath exhaled
through the nose is measured for an isotope, C13, which is released
in carbon dioxide. The less C13, the higher the likelihood of poor
liver function, said Exalenz CEO Lawrence Cohen.
"We've got extremely good results that correlate with biopsies," he
said.
(Reporting by Bill Berkrot; Editing by Michele Gershberg and John
Pickering)
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New
market for liver disease spawns race for better testing
