Home Depot not long ago, Jay Konduros was hefting a 40-pound
box of shelving into his cart when it suddenly slipped — and
blood welled up from a gash in his shin, and his mind flashed
back to a lifetime of caution and pain.
minor mishap with a snow-shovel that put him out of commission
for weeks, his leg so swollen he could not see his knee.
days he told friends he could not come out to play, but didn’t
want to say why. The times his mother rushed him to the
hospital, carrying him because he couldn’t walk.
then, staring at his gashed shin at Home Depot, he thought
this time might be different.
was born with hemophilia, the blood clotting disorder.
he banged up an arm or leg, and sometimes even without any
apparent injury, he might develop the swelling and pain that
are the hallmarks of dangerous internal bleeding. Each time it
happened, he had to infuse himself with costly synthetic
clotting factor — a lifetime tab that so far had run into
last year, the 52-year-old was among the first in the world to
receive a one-time, experimental treatment: a dose of
genetically engineered particles that would enable his liver
to make enough clotting factor on its own.
was lucky, this one-shot treatment — developed by Spark
Therapeutics, a biotech startup spun off from Children’s
Hospital of Philadelphia — would ward off his disease for
what could be many years.
Depot accident, near his home outside Toronto, represented an
unplanned test of the treatment. In the hours and days after
the heavy box slammed into his leg, Konduros waited and
was no bruising. No swelling. No debilitating pain.
kind of smile and think, ‘Ok, that’s abnormal,’ "
A. High’s first extended experience treating patients with
hemophilia came during an especially dark period for the
advent of donated clotting factors had revolutionized
treatment for a condition that once meant a shortened, painful
life. But in the 1980s, scientists learned that HIV could be
transmitted through these donated blood proteins. As many as
half of the patients in the U.S. — the condition affects
mostly males — would become infected with HIV. Some also
contracted hepatitis C, another serious blood-borne illness.
physician then in her first faculty job at the University of
North Carolina at Chapel Hill, wondered if the answer lay in
the young field of genetics.
desperately wished that we had a better treatment," she
said in a recent interview.
long before the days of high-speed gene sequencing machines,
she and colleagues announced a breakthrough. They pinpointed
the mutation that caused a form of the disease, called
hemophilia B, in dogs.
1990s, by then at Children’s Hospital of Philadelphia, High
pursued the idea of treating hemophilia with gene therapy:
infusing patients with "vector" particles that
carried the genetic recipe for clotting factors they could not
make on their own.
her colleagues got the treatment to work first in mice, then
in dogs. Then in 2006, they announced it had worked in humans,
but only temporarily.
because the vectors carrying the recipe were made from
viruses, which had provoked a response from the patients’
are an ideal tool in the field of gene therapy, as they are
equipped with the natural ability to invade a human cell and
deliver DNA. In the case of the hemophilia patients, the viral
vector was loaded with the DNA recipe to make clotting factor.
Also key: it was a type of virus that did not cause human
the outer shell of the particles triggered an immune response.
Within weeks of treatment, the patients’ bodies destroyed
the enhanced liver cells, and the benefits of the treatment
team, and others, went back to work. In 2013, she decided the
best pathway to success was through the private sector.
Children’s Hospital investing $50 million, High co-founded a
biotech startup called Spark Therapeutics.
its aim to produce one-shot treatments for hereditary
diseases, the company chose a fitting ticker symbol on the
NASDAQ stock exchange: ONCE.
time Jay Konduros was an adult, the standard treatments for
hemophilia had made great strides. Careful screening and
purification methods all but eliminated the risk of
contracting disease from donated clotting factors.
came the development of synthetic clotting factor, which was
judged to be even safer. And unlike the early days, he could
administer the treatment at home. In his case, that was
clotting factor IX, the protein that is deficient in people
with hemophilia B.
doctor told him it cost $30,000 (about $22,500 in the U.S., at
current exchange rates) for enough of the precious fluid to
treat a typical injury, a cost picked up by Canada’s
national health service.
made me kind of gulp a bit," he said. "You do think,
‘Damn, I’m glad I live in Canada.’ "
on the severity of an injury, he might get away with one or
two treatments. But if he waited too long, or misjudged the
amount, it meant trouble.
shoveling snow two years ago, the blade caught on the ground
and the handle rotated sideways, jamming hard into his thigh.
He took two treatments at home, yet ended up in the hospital
for 10 days, and had to walk with a cane for months.
November 2015, Konduros’ doctor told him about High and the
gene therapy at Spark.
latest version of the treatment, the vector was programmed
with the DNA of a super-clotter — a patient in Padua, Italy,
whose clotting activity levels were four to eight times
meant patients could make do with just one-fourth the dose of
the viral particles, greatly reducing the risk of an immune
came to Philadelphia in June. Lindsey George, a hematologist
at Children’s Hospital, administered the infusion, known as
SPK-9001. Trillions of the special particles traveled through
a tube into his arm, destined for his liver.
is one of 10 patients to get the treatment so far. Spark has
announced results for nine, all of whose ability to make
clotting factor has soared. Two patients experienced an immune
reaction and their factor activity levels, after rising,
started to decline. But their levels stabilized after they
were given steroids, High says.
seen their factor activity levels climb from 1 or 2 percent
well into the double digits; short of normal, but still
considered a big improvement. At those levels, patients do not
experience spontaneous bleeds, and most injuries are not a
problem, either. As of Nov. 30, the patients had all but
eliminated the use of synthetic clotting factor, for a
collective estimated savings approaching $2 million.
physicians not involved with the study are impressed.
pretty exciting news," said Jason A. Taylor, associate
director of the Hemophilia Center at Oregon Health &
Science University. "We’re still not exactly sure what’s
going to happen in the long term."
should this therapy cost? High won’t say, but some analysts
have said they expect the company to aim for a treatment price
in the range of $1 million, an eye-popping cost even in an era
of high drug prices. Yet this is potentially a one-time fix
for a disease that can cost many millions to treat over a
lifetime. Some in the gene therapy field have discussed a
the month after Konduros got his infusion, the U.S. Food and
Drug Administration granted "breakthrough" status to
the therapy, allowing for an expedited review process.
giant Pfizer has bought the right to sell the therapy, if it
is approved, and has paid Spark $50 million to date. The
startup is eligible for up to $230 million more plus
the company’s president and chief scientific officer, is
all of these people, it’s a little bit like they come in,
they get the infusion, they walk out, and they leave their
hemophilia behind," she said. "How long will it
last? I don’t know. Were they very brave to volunteer?
STORY CAN END HERE)
refuses to call it a cure, since the therapy is too new to be
certain how long the effects will last. In dogs who got the
treatment, the improvement has lasted more than a decade so
who runs a bakery in Kitchener, Ontario, calls it "The
Philadelphia FIX," playing on the abbreviation for factor
speaking out about it because already he sees a future when
the disease is no big deal. He equates it to the huge advances
made with vaccines that have turned childhood scourges like
polio into distant memories.
say ‘What’s hemophilia? Apparently people in the past had
it,’" Konduros said. "They won’t know what they’re