Woman misdiagnosed with MS and enrolled in Tysabin clinical trial dies
By Evelyn Pringle
Online Journal Contributing Writer
Mar 3, 2006, 01:24
It's always about
money. Despite an annual cost of $23,500, initial sales of Tysabri were
booming. As a once-a-month drug administered by a doctor, it received
fast-track approval in late 2004. When it was withdrawn from the market three
months later, 5,000 patients were on it and 15,000 more were awaiting insurance
verification for the first dose.
Biogen Idec of
Cambridge, Mass., and Elan, in Dublin, Ireland, viewed their new product as a
potential blockbuster. The companies needed just 20,000 patients to break even,
according to the February 18 Los Angeles Times.
And Wall Street
projected yearly sales to one day reach $3 billion.
However, the rosy
financial projections went up in smoke in February 2005, when the drug makers
suddenly withdrew Tysabri from the market after five patients contracted a rare
brain disease called PML, short for Progressive Multifocal Leukoencephalophy.
In reaction to the
news, Biogen stock dropped 43 percent and Elan shares plunged 70 percent,
according to the LA Times. The drug makers are currently awaiting a decision by
the FDA on their request to allow Tysabri back on the market which is expected
to come after hearings are held this month.
frequently reported other adverse events in the Tysabri clinical trials,
overshadowed by the reports of PML, are listed by the FDA to include
infections, severe or life threatening allergic reactions, depression
(including thoughts of suicide), and gallbladder problems.
events occurred at rates ranging from 0.8 percent to 2.1 percent," the
(MS) is a central nervous system disease that can lead to muscle weakness,
difficulty concentrating, slurred speech and paralysis. About 400,000 Americans
and 2.5 million people worldwide are believed to be affected by MS. It is more
common in women than men and usually strikes between the ages of 20 and 50,
according to the National Multiple Sclerosis Society. The disease causes the
body�s immune system to rebel by attacking, inflaming and damaging its own
Anita Smith, a
patient enrolled in the Tysabri study for treatment of MS, died from PML, and
another patient taking Tysabri for Crohn's disease also died of PML.
According to WebMD
Medical News, "PML is a progressive disease of the brain and spinal cord
that primarily affects people with weakened immune systems."
is caused by a virus that destroys the sheath that covers the nerves," it
said. "Symptoms include mental deterioration, vision loss, speech
disturbances, and movement abnormalities or paralysis," WebMD reports.
A March 2, 2005,
article by Forbes.com titled, �The Virus That Took Down Tysabri," explains
how a specific virus causes the development of PML.
The JC virus
discovered in 1971, was named with the initials of the patient in whom it was
found. The virus is present in almost everyone, according to the article, but
only destroys the brain when something damages the immune system and allows the
virus to run rampant.
By suppressing the
immune system, Forbes says, Tysabri allows the JC virus, ordinarily latent in a
patient�s kidney, to travel to the brain via the bloodstream, where it begins
first description of the disease in 1958, it had remained a rare
occurrence," Forbes said, "seen mostly in organ transplant patients
whose immune systems were suppressed by drugs." About 5 percent of people
with full-blown AIDS also develop PML
On February 25, in a
new development, News Infirno.com announced a major court ruling in
Massachusetts in a wrongful death action filed on behalf of the estate of the
46-year-old wife and mother of two, Anita Smith, that ordered Biogen to produce
all medical records on Ms Smith immediately.
It seems that
although she had been diagnosed and treated for MS, an autopsy revealed that Ms
Smith never had MS, thereby making her enrollment in the trial problematic at
best News Inferno reported.
The allegations in
the lawsuit complaint contain a number of interesting facts. In February 2000,
Anita Smith was diagnosed with MS and her neurologist began treating her with
Avonex, another MS drug manufactured by Biogen.
In April 2002, she
was enrolled in a clinical trial and began receiving Tysabri in addition to
Avonex. During her treatment with Trysabri, she received 30 IV infusions
beginning on April 12, 2002 and ending in January 2005.
fast-track FDA approval in November 2004, the same month that Ms Smith began to
suffer severe neurological problems.
She was hospitalized
on February 12, 2005, when diagnosed with PML, and died on February 24, 2005.
Sales of Tysabri were suspended on February 28, 2005.
An autopsy confirmed
that Anita Smith died of PML.
Based on animal and
other studies, some of the scientists who developed Tysabri concluded as far
back as 1992, that it was far too dangerous for use in humans. Dr Lawrence
Steinman, a professor of neurology at Stanford University who participated in
an animal study that led to the development of Tysabri, told the New York Times
on March 1, 2005, that the FDA should not have approved the drug based on one
He said the risk of
serious infections like PML was "unfortunately logical" given that
Tysabri works by interfering with the immune system.
�I�m shocked that it
happened so soon," he told the Times, "but I knew it was going to
happen sooner or later.�
Critic say the Anita
Smith case highlights the problems with the way MS drugs are being tested.
years," the February 18 LA Times said, "drug companies have been
trying out medicines on people with mild symptoms or none at all at the time of
treatment, several experts say, including some who, like Smith, might not have
Ms Smith was
diagnosed with MS after a bout of weakness in her right leg, followed by
blurred vision. "Although the symptoms disappeared," the LA Times
said, "she started taking injections of Avonex."
In fact, most of the
1,171 patients in Ms Smith's trial suffered no disabilities, according to FDA
documents reviewed by the Times.
broadened the market for MS drugs but, critics say, put patients who don't need
powerful new medicines at risk.
Dr Steinman and
another Stanford neurologist, Dr Annette Langer-Gould, have urged the FDA to
tighten criteria for selecting patients for MS drug trials.
explained how Biogen led the push toward earlier treatment of MS with a study
on Avonex six years ago in patients who did not meet the clinical definition of
MS in effect at the time.
trial, which showed that Avonex could delay relapses, benefited patients
because it led to earlier treatment," she told the Times, "it also
benefited Biogen Idec by expanding the market for Avonex."
Dr Langer-Gould said
the study did not raise concerns because the drug was already on the market and
considered safe. But she told the Times that she worries that patients with
mild cases of MS face greater risks from experimental drugs than from their
"What was the
rush to treat these patients?" she asked.
Dr Abhijit Chaudhuri
a London neurologist, shares her concern. "Patients with mild MS and who
are fairly stable generally don't get that bad," he told the Times.
"Why on Earth would you go into a treatment trial with the possibility of
side effects and complications when you don't expect to get much worse?"
Dr Steinman agreed.
"People with no active disease -- in other words, people who are doing fine
-- shouldn't be given an experimental drug with unknown risks," he told
In addition to the
unnecessary risks associated with the MS drugs, they are extremely expensive
and patients who believe they need the drugs are in effect being bribed into
recruitment for the clinical trials.
Although Ms Smith's
insurance covered some of the cost of the drugs she was led to believe she
needed, the couple still had to pay about $1,000 a month, her husband told the
He said the
motivation for entering the Tysabri trial was largely financial, because the
neurologist told the couple that as a trial participant, Ms Smith could receive
the Avonex for free.
If true, the
revelation of the money trail involved in this trade-off may turn out to be the
show stopper in the eyes of the jury.
According to the
lawsuit's complaint, when Ms Smith's neurologist misdiagnosed her with MS, and
recruited her for the study, the doctor was being paid for serving as an
"Investigator" in the Tysabri clinical trial.
For information for injured parties go to Lawyers and
Copyright © 1998-2006 Online Journal
Email Online Journal Editor