Alhamdulillah, akhirnya tuntutan Ubat Kimoterapi Sutent yang ku mohon sejak Januari 2010 telah diluluskan. Ku maklumkan kepada Pegawai Kebajikan Hospital USM. Aku mesti memindahkan duit dari Akaun Maybank ku ke Akaun CIMB syarikat Farmasi Prima Sdn.Bhd. Ku minta dicetak penyata akaun tetapi Maybank mengenakan caj RM10.00 untuk semuka helain. Ku merungut juga kerana kalau kemaskini buku akaun dulu cuma percuma. Sekarang Maybank tak beri buku akaun lagi. Nak cetak kena caj. Tak adil. Nak guna maybank2U dah kena blok kerana lama tak guna.
Selepas confirm duit dah masuk, ku membuat Kiriman Wang. Jumlahnya RM54,000.00 untuk 3 bulan uabt. Moga penyakit ku sembuh selepas 3 bulan memakannya Ku tak mahu membebankan kerajaan dengan kos ubat yang tinggi dan paling penting tak sanggup lagi menderita penyakit kanser ini.
Moga Allah kabulkan doa ku ini.
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It was the first time
the agency has approved a new oncology
product for two cancers simultaneously.
Sutent, which
received a priority review and was
approved in less than six months, is a
tyrosine kinase inhibitor. The
once-daily, 50 mg. capsule blocks
several enzymes that deprive the tumor
cells of the blood and nutrients needed
to grow.
“Today’s approval is
a major step forward in making
breakthrough treatments available for
patients with rare and difficult to
treat forms of cancer,” said Dr. Steven
Galson, director of FDA’s Center for
Drug Evaluation and Research. “New
targeted therapies such as Sutent are
helping FDA expand options for patients
for whom there are limited
alternatives.”
Sutent won approval
for the treatment of Gleevec-resistant
GIST and for GIST patients unable to
tolerate Gleevec, the current treatment
for GIST. In clinical trials,
researchers did an early analysis of
data that showed Sutent delayed the time
it took for tumors or new lesions to
grow. Specifically, the median
time-to-tumor progression for patients
treated with Sutent was 27 weeks
compared to six weeks for patients given
a placebo.
Of 312 clinical trial
participants, 207 received Sutent, while
105 were given placebos.
Typically, patients
in cancer trials are not given placebos
because it is considered unethical to
deny them effective treatments. But
Sutent maker Pfizer said a third of the
patients were given placebos in this
trial because no standard drug is known
to work against such stomach tumors once
they develop resistance to Gleevec.
When it became clear
that patients taking Sutent were
surviving longer than the placebo group,
all patients in the study were allowed
to start taking Sutent.
FDA also granted
accelerated approval for Sutent in the
treatment of patients with advanced
renal cell carcinoma (RCC). In contrast
to the approval for GIST, which was
based on the drug’s ability to delay the
growth of the tumors, this approval was
based on Sutent’s ability to reduce the
size of the tumors in patients. An
overall response rate ranging from 26 to
37 percent was found in patients with
metastatic kidney cancer whose tumors
had progressed following cytokine-based
therapy.
Pfizer is studying
the drug for use in treating other
cancers, including colorectal, breast
and lung cancer.
Pfizer says it
expects the average cost of Sutent per
six-week treatment cycle to be about
$4,000, putting the annual cost of
treatment at about $38,000. The drug is
expected to be available to patients
Feb. 3, and will come in 12.5 mg., 25
mg. and 50 mg. capsules.
Patients and
physicians can visit www.sutent.com or
phone FirstRESOURCE at (877) 744-5675
for information about patient assistance
for those who don’t have drug coverage
and for information about reimbursement
issues or appeals assistance.
The FDA said in a
statement that it has a long-standing
commitment of providing patients with
serious and life-threatening diseases
access to safe and effective treatments,
in some cases prior to FDA approval.
In the GIST clinical
trial, significant clinical benefit was
determined through an interim analysis
of data, thereby allowing researchers to
convert all patients in the trial to
treatment.
“Expanded access
programs have proven to be an effective
way to get treatment to patients who
need it most, especially in cancer,”
said Ellen Stovall, president of the
National Coalition of Cancer
Survivorship. “There needs to be a
greater awareness among patients and
doctors about both the option to
participate in clinical research as well
as in these expanded access programs in
order to make promising new therapies
available to as many patients as
possible.”
Pfizer said the most
commonly reported side effects included
diarrhea, nausea, stomatitis, dyspepsia,
and vomiting. Patients also experienced,
fatigue, high blood pressure, bleeding,
swelling, and altered taste.
Hypothyroidism was also observed.
Skin discoloration
possibly due to the drug color (yellow)
occurred in approximately a third of
patients. Other possible dermatologic
effects may include dryness, thickness
or cracking of skin, blister or rash on
the palms of the hands and soles of the
feet.
Pfizer, which
acquired Sutent in 2003 through its
purchase of Pharmacia Corp., has said it
intends to become a major player in the
oncology arena. It is now far better
known for drugs such as Viagra and
cholesterol fighter Lipitor.
GIST Patient Susan Farmer
Axel Ullrich, founder of Sugen
Peter Hirth, a former Sugen president
3-D Model of a Melanoma Drug
Dr. Keith Flaherty of MassGen Hospital
March 5 (Bloomberg) --
George Demetri had witnessed
countless near-death experiences in his career as a cancer
doctor. This time, the life of a drug was on the line.
It was called SU11248, and
Pfizer Inc. had just acquired
the company developing it. Tumors were shrinking in two thirds
of the digestive tract cancer patients in the clinical trial
Demetri had been running since February 2002. One dying man’s
malignancy had stopped growing so suddenly after five doses that
it was a “miracle,” the oncologist said.
“Interesting parlor trick you’ve got there, but this isn’t
a market,” he said Pfizer executives responded when they
learned of the results. The trial’s patients had a type of
cancer accounting for less than 1 percent of new U.S. cases
diagnosed every year. “We are probably going to shut this
down,” he said they warned.
Still, a Pfizer official agreed to accompany him to a
December 2003 meeting with U.S. Food and Drug Administration
regulators, who were encouraged by the data and sanctioned a
second, larger trial. “Credit to Pfizer for realizing it had a
winner,” Demetri said. Company spokesman
Chris Loder declined
to comment on the doctor’s recollection of events.
In January 2006, Sutent became the first treatment
simultaneously approved for two cancers: gastrointestinal
stromal tumors, or GIST, and renal cell carcinoma. A pill that
almost landed on the scrap heap of medicine has, according to
New York-based Pfizer, since generated $2.6 billion in
sales.
‘It’s Not Sustainable’
Sutent is part of an explosion of treatments that attack
cancer at the molecular level, holding the promise of turning
intractable malignancies into chronic diseases like diabetes or
HIV. Targeted therapies are already extending life -- and adding
to the cost of end-of-life care, which in the case of Sutent
could be on the order of $48,720 a year.
The story of the drug, which took 15 years to get from
theory to therapy, shows why such medicines, which have limited
periods of effectiveness, are so expensive that some governments
resist paying for them. On the advice of
the British National
Institute for Health and Clinical Excellence, the U.K. National
Health Service refused for three years to buy Sutent for its
patients. The price, the institute decided in 2006, was simply
too high for the amount of time it bought.
“We are all worried that it’s not sustainable,” said
Demetri, 53, director of the Ludwig Center at the Harvard
University-affiliated
Dana-Farber Cancer Institute in Boston, in
an interview. “Ultimately, our country may say, ‘OK, we can
have these expensive cancer drugs or we can have vaccines for
our kids -- what do you want?’”
Just 29 Days
For those who can afford a pill with a
retail price of about
$200, or whose insurer will cover it, Sutent is a life extender.
The metastatic cancer of GIST patients on Sutent was held in
check for about 21 weeks longer than that of patients who began
a clinical trial on a placebo,
according to Pfizer.
While about a third of those with GIST who switch to Sutent
get no benefit, the drug has been a lifeline for thousands,
Demetri said, often buying enough time for a new medicine to
roll out of the targeted therapy pipeline.
Terence Foley, a musician and teacher living in
Philadelphia, was one for whom it offered no benefit. A
combination of
Genentech Inc.’s Avastin and
Bayer AG’s Nexavar
helped keep his kidney cancer at bay for 17 months, but he died
29 days after his first dose of Sutent.
A Grandson’s Birthday
“I didn’t see it coming,” said Keith Flaherty, 39, a
protégé of Demetri’s who was Foley’s oncologist at the time of
his death in December 2007 at age 67. Why didn’t Sutent extend
his life? Perhaps, Flaherty said, his patient’s tumor was made
up of preponderance of cells that were Sutent-resistant.
Susan Farmer was a different case.
Sutent worked for the retired Rhode Island public
television executive, who has fought metastatic GIST for seven
years with what doctors call daisy chaining. When her malignancy
no longer responds to a treatment, she switches to another,
moving from one targeted therapy to the next to the next. She
took Sutent, the second in her chain, for 18 months.
“I am alive because of these drugs,” said Farmer, 67.
She credits
Novartis AG’s Gleevec, the first, for allowing her
to see her second grandson born in 2005. Sutent kept her well
for his fifth birthday.
The company that developed Sutent,
Sugen Inc., got its
start in Redwood City, California, in 1991. Cancer treatment at
the time had been largely unchanged for decades. Doctors bombed
tumors with a toxic chemical mix and hoped for the best. They
rarely got it, and patients suffered chemotherapy side effects
including hair loss and debilitating nausea.
A Kinases Race
The idea propelling Sugen had been postulated 20 years
earlier by Harvard Medical School’s
Judah Folkman, who became
director of vascular biology at Children’s Hospital Boston. His
theory was that malignant solid tumors depended on a genetic
corruption of angiogenesis, the blood-vessel building process.
Shut down angiogenesis, his thinking went, and the tumors would
starve for lack of blood.
By 1989, scientists had identified a protein -- known as a
kinase -- as the primary driver of angiogenesis: vascular
endothelial growth factor, or VEGF. The discovery set off a race
to isolate others and develop inhibitors.
One of Sugen’s founders,
Axel Ullrich of Germany’s Max
Planck Institute of Biochemistry, had cloned human insulin as a
researcher for South San Francisco-based Genentech. Ullrich, now
66, also helped discover the gene HER2, thought to be
responsible for runaway cell replication in some cancers.
Gen for Genetics
His partner was Joseph Schlessinger, then head of the New
York University Medical School pharmacology department and now
director of Yale University’s department of pharmacology.
Schlessinger, 64, did research at Rhone-Poulenc Rorer Inc.
before it became part of
Sanofi-Aventis SA, and worked on the
technology that led to ImClone Systems Inc.’s colon cancer
treatment Erbitux and other drugs.
The company was named after them: S for Schlessinger and U
for Ullrich, followed by gen, for genetics.
Sugen’s first chief executive officer was
Stephen Evans-
Freke. He had raised more than $600 million for Thousand Oaks,
California-based Amgen Inc., and other biopharmaceutical
startups, according to the Web site of
Celtic Pharma Management
LP, a Hamilton, Bermuda-based private-equity firm where Evans-
Freke is a managing general partner. Evans-Freke pulled together
$2.5 million in venture capital for Sugen, which raised $20
million when it went
public in 1994.
$100 Million a Year
The hunt for kinase inhibitors was slow and expensive,
Ullrich said in an interview. For one thing, all the kinases had
to be identified, which Sugen did by building a “kinome,”
mapping the 500 or so that inhabit the body.
Another challenge was that kinases exist at the core of
cellular biology, sharing space with
adenosine triphosphate, or
ATP, the very engine of intracellular energy.
“The worry was that you couldn’t drug these kinases
without shutting down every energy-generating process in the
body,” Demetri said. “You’d kill people faster than the
disease would.”
A solution required designing drug molecules so precise
they could slip into the pockets of specific kinases without
interfering with ATP. Sugen scientists bombarded cancer-driving
proteins with synthesized chemical compounds to figure out which
of them showed promise as kinase inhibitors.
By 1998, Sugen was “burning through about $100 million a
year,” and running out of money for the clinical trials that
are fundamental to bringing a drug to market, according to
Peter
Hirth, who was president at the time.
Betting on VEGF
Pharmacia & Upjohn Inc., based in Bridgewater, New Jersey,
stepped in with the cash in 1999, buying Sugen for $650 million.
Genentech, acquired last year by
Roche Holding AG, had
shown that targeted therapy could be a commercial success after
FDA approval in 1998 of the metastatic breast cancer drug
Herceptin. It attacks the HER2 gene, the one Ullrich helped
find, and was the first kinase inhibitor on the market.
In May 2001, Novartis, based in Basel, Switzerland, secured
FDA approval for Gleevec, which worked by knocking out the main
molecular driver in chronic myeloid leukemia. Genentech was by
then in trials with what it would call Avastin -- used today
against five cancers -- and early results indicated it would
prove that VEGF inhibitors could thwart angiogenesis.
Sugen’s bet was on targeting VEGF, and of the 50,000
compounds scientists threw at it in the lab, exactly three
seemed promising, according to Ullrich and Hirth.
A Dirty Inhibitor
One of the three -- christened SU5416 because it was the
5,416th substance tried out -- was given in 2001 to 350
colorectal cancer patients. So few responded that the trial
“failed statistically,” according to Ullrich.
The scientists concluded SU5416 wasn’t soluble enough to
slip with adequate dosage into its molecular target. They turned
to SU11248, the 11,248th of the compounds tested, and tweaked
it. The adjustments “made it less specific,” and SU11248 went
after VEGF and also as many as 200 other kinases, Ullrich said.
Because protein kinases regulate many normal cell signaling
functions, not just those driving cancer, the drug might block
healthy activities, too, Ullrich said.
“Nobody was sure they wanted a dirty kinase inhibitor like
SU11248,” Ullrich said.
Then Sugen tested it in a 2002 “basket trial,” so named
because people with a variety of cancers took part. SU11248 was
sent to oncologists worldwide, and in what Ullrich called a
“lucky accident” a Paris doctor gave it to three kidney cancer
patients. Two “had outstanding responses,” he said.
The Lipitor Company
The basket trial occurred before Pfizer closed its $58
billion acquisition of Pharmacia in April 2003. Pfizer, which
disbanded Sugen as a unit, decided to finance trials focusing on
renal patients. Demetri was wrapping up his clinical evaluation
of SU11248’s ability to target kinases driving GIST for patients
who had run out of treatment options.
After Pfizer learned about his patients’ “spectacular”
results, Demetri said he was quizzed on his estimate that the
market for the drug would be only a few thousand patients.
“A few thousand? Look, we’re the Lipitor company, we’re
looking for a few million,” he said Pfizer executives told him.
Lipitor, Pfizer’s cholesterol pill, is the world’s top selling
drug with more than $11.4 billion in 2009
revenue.
At the December 2003 meeting, FDA officials wouldn’t
accelerate the SU11248 approval process, because standard scans
didn’t show tumors were shrinking definitively enough, Demetri
said. Pfizer agreed to fund placebo trials.
A Vampire Cancer
The drug would be given to two-thirds of a group and sugar
pills to the rest -- rare in oncology where lives are on the
line. The FDA agreed that sugar-pill patients whose tumors grew
would be given the real drug. The trial started in January 2004.
Within a year, every placebo patient had been switched
because of “staggeringly statistically positive” results,
Demetri said. Tumor growth in those taking SU11248 halted for 27
weeks compared with six weeks for those on sugar pills,
according to FDA data.
For Farmer, the trial’s success meant more life.
Farmer, who served two terms as Rhode Island secretary of
state, was diagnosed with
GIST in October 2001 after an
abdominal tumor burst and hemorrhaged. A surgeon removed the
growth -- it was “about the size of a shot put,” she recalled
-- but by January 2003 the malignancy had spread to her liver.
Invincible to most treatments, GIST was known as a kind of
vampire cancer whose cells “have an anti-death pathway turned
on,” Demetri said. “They don’t know how to die, which is why
chemotherapy doesn’t work.”
‘Heart Flutters’
Doctors began building Farmer’s daisy chain with Gleevec,
which shrank her liver tumors within a month of her first dose
in February 2003. Side effects included puffy eyes, muscle
cramps, diarrhea “and chemo brain,” she said. “I thought I
was getting Alzheimer’s.”
A scan in April 2008 showed two of the largest growths were
active once more. Gleevec’s effectiveness had run out.
So Farmer started on Sutent. This time, her teeth became so
sensitive she couldn’t brush. Eating sugar hurt them. She
couldn’t catch her breath.
“I got heart flutters,” she said. “I got headaches. It
hurt to talk. One day I just sat there with my Sutent in my hand
saying I can’t possibly have one more of these things. It may
give me one more day of life, but it felt like death. I made the
decision I was just going to stop and not take it.”
She changed her mind after a scan showed the tumors
shrinking once more.
Every Customer’s Premium
Her dose was reduced, and the side effects abated. The
cancer didn’t grow again until last October, when Sutent was
replaced with Novartis’s Tasigna, developed as a Gleevec backup
and approved in November 2007.
Should Tasigna fail, two treatments in clinical trials seem
promising, Farmer’s doctors have told her. She said she would be
willing to keep the daisy chain going.
For people who have private health insurance like Farmer’s
or who qualify for
Medicare, the tax-funded program for
Americans over 65, Sutent isn’t a personal financial issue.
UnitedHealth Group Inc., the world’s largest health
insurance provider, pays for every cancer treatment for the use
for which the FDA approved it, and UnitedHealth’s competitors do
the same, said Lee Newcomer, senior vice president of oncology
at the Minnetonka, Minnesota-based company.
“Pfizer knows very well I can’t refuse to cover this
drug,” Newcomer said in an interview.
Rationing by Pricing
The cost of reimbursing for Sutent and other targeted
therapies is factored into every customer’s premium, which
results in a kind of rationing that is putting life-extending
treatments beyond the reach of more and more Americans, he said.
“Everyone’s premium goes up because we layer that across
everyone we insure,” he said. “All the recent health policy
talk is that in the U.S. we don’t ration, but that isn’t a true
statement. We just keep pricing more and more people out of the
ability to afford health insurance. We have chosen to ration by
just pricing some people out.”
To decide what to charge for targeted drugs, some companies
use as a benchmark kidney dialysis -- for which Medicare pays a
per-patient average of $71,000 a year -- because it is “another
heroic but effective way of keeping people alive,” said
Tim
Byers, associate dean of public health practice at the Denver-
based Colorado School of Public Health.
The “general estimate of the cost” of Sutent for the
average kidney cancer patient is $50,000 a year, according to
UnitedHealth.
‘Most Liberal Nation’
Pfizer won’t disclose what was spent bringing Sutent to
market or the profit it makes off the drug, Loder, the
spokesman, said. The company charges wholesalers an average of
less than $5,100 for a month at the highest dosage, he said.
Pfizer rose 15 cents, or less than 1 percent, to close at $17.48
today in New York Stock Exchange composite trading.
U.S. regulators don’t take pricing into consideration when
evaluating whether a therapy should be sold to the public.
“The U.S. is by far the most liberal nation in letting the
market decide the fate of these drugs,” said Flaherty, director
of developmental therapeutics at Massachusetts General Hospital
Cancer Center in Boston, affiliated with Harvard Medical School.
In the U.K., where the tax-funded
National Health Service
covers all residents, the calculus is different.
“This drug was way outside of what we considered cost
effective,” said
Peter Littlejohns, the clinical and public-
health director for Britain’s health institute, in an interview
about the 2006 decision again Sutent. “The average life
expectancy was in terms of months, not years, and there will be
some who have no benefit from it.”
Daisy Chaining Momentum
The institute reversed its ruling on Sutent last year,
persuaded by pressure from oncologists and patient advocacy
groups, a campaign by Pfizer and the company’s promise to
provide the first round of prescriptions to National Health Plan
patients at no cost.
At the same time, the U.K. rejected two other targeted
therapies covered by Medicare and U.S. insurers: Nexavar for
liver cancer and Avastin for advanced bowel cancer. Nexavar was
estimated to cost 65,900 pounds ($102,000) for every “quality
adjusted year of life,” while for Avastin it was 74,999 pounds,
according to institute reports.
The drugmakers are appealing.
The success of targeted therapy relies on a steady stream
of approvals of new drugs and on insurers being willing to pay
for them. Patients need alternatives because tumor cells that
survive one drug’s attack can regroup and grow, and only a new
medicine can work on them.
‘More Expensive Treatments’
With daisy chaining the momentum is undeniable, according
to Flaherty. In metastatic kidney cancer, for instance, Sutent
and five other drugs made available in the last four years moved
the average survival rate from 14 months to a range of 36 to 48
months, Flaherty said.
“Improving cancer survival rates are a real success story
that sometime get lost in the noise over our health-care
system,” said Douglas Blayney, president of the Alexandria,
Virginia-based American Society of Clinical Oncology, the
largest U.S. organization of cancer doctors. “Targeted drugs
are driving that survival in a major way.”
The FDA has approved 25 targeted agents since 1998, the
agency’s Web site shows. With hundreds in development, 40 more
could be on the market by 2015, according to a 2008 report by
the Boston-based
Tufts Center for the Study of Drug Development,
which is affiliated with Tufts University.
‘The Deep End’
As pharmaceutical companies continue to produce these and
other “more advanced, and more expensive treatments,” U.S.
cancer-fighting costs will rise faster than overall medical
spending, according to the
National Cancer Institute in
Bethesda, Maryland. Cancer treatment spending rose 75 percent in
the decade ending in 2004, to $72.1 billion, according to a 2007
NCI report, the latest data available.
Medicare already devotes about a quarter of its budget --
now $450 billion -- to care in the last year of life, according
to the policy
journal Health Affairs. As baby boomers age and
fall under the U.S. tax-funded program, they’re ushering in a
new era of spending.
People 65 and older have 10 times the cancer rate and 16
times the cancer mortality rate of those younger,
NCI data show.
Cancer is the No. 2 killer behind heart disease, responsible for
one in four non-accidental deaths, according to the
Centers for
Disease Control and Prevention in Atlanta.
That number might fall as researchers invent better
diagnostics that let doctors more quickly identify a cancer’s
genetic driver and make smarter drugs that cleanly knock out
cancer drivers, according to Flaherty.
“If we can get one more drug, can we push the tumor so far
into hibernation that, while not curing it, we’re managing it as
a chronic disease?” he said. “We think that’s possible.”
To contact the reporters on this story:
Ken Wells in New York at
kwells8@bloomberg.net;
Shannon Pettypiece in New York at
spettypiece@bloomberg.net
To contact the editors responsible for this story:
Robert Blau in Washington at
rblau1@bloomberg.net;
Reg Gale in New York at
Rgale5@bloomberg.net
FDA
worked with Pfizer, maker of Sutent, to
offer an expanded access program prior
to approval, making the product
available to patients not enrolled in a
clinical trial. Currently, more than
1,700 U.S. patients are being treated
with Sutent through the expanded access
program.