'Right-to-try'
for the terminally ill
WASHINGTON — Fifteen-year old Austin Leclaire and his brother Max, 12, of
Pembroke, Mass., share the deadly degenerative diseaseBut over the course of the past 144 weeks, the boys' physical
conditions have progressed in opposite directions.
Max has regained functions — he has abandoned his wheelchair and can now
run, tote his own backpack to school and even ride a bike. Austin's
capabilities are diminishing. He cannot walk at all, and he's lost the ability
to brush his teeth or hold a water bottle. He expects that soon he won't be
able to play drums anymore, one of his few remaining physical pleasures.
The difference in their trajectories is that Max has been in a clinical
trial for nearly three years, during which he has been given weekly infusions
of the experimental drug eteplirsen, manufactured by Sarepta Therapeutics Inc.
Austin was deemed unqualified to get the drug because of his more advanced
condition.
Withholding experimental drugs from the most gravely ill has fueled several
states to pass so-called "right-to-try" legislation that would make
these drugs available without Food and Drug Administration approval to
terminally ill patients with no other options.
Some critics of the yearslong FDA drug approval process, with its
requirement for multiple clinical trials, contend that it is much longer than
it should be, thereby keeping some promising drugs from those who might
benefit, particularly those, like Austin, with time running out. The Tufts
Center for the Study of Drug Development says it normally takes 5 1/2 to 10 1/2
years for a drug to receive FDA approval.
Because of that, Colorado, Missouri and Louisiana all passed right-to-try
legislation this year that would enable those with terminal illnesses and no
other treatment options to secure investigational drugs after their first phase
of clinical trials (there usually are at least three) before final FDA approval
if the drug manufacturer is willing to provide them. Arizona voters will decide
a similar measure in a referendum in November.
The legislation passed overwhelmingly and with bipartisan support, often
after lawmakers heard anguished testimony from terminally ill patients or their
families.
The laws would cut the FDA out of the process, at least in terms of an individual
terminally ill patient. The decision would be left entirely in the hands of the
patient, the doctor and the drug company.
Whether these laws would withstand a court challenge is an open question.
Typically, state laws cannot supersede federal statutes. Even if the laws don't
withstand a challenge, advocates say, they may serve a valuable service in
spotlighting the issue.
"(A lawsuit) wouldn't be all bad news because it would further elevate
this issue in the public arena and put pressure on Congress and the FDA to make
this change and literally save thousands of lives every year," said Frank
Burroughs, head of the Abigail Alliance for Better Access to Developmental
Drugs, which he founded 13 years ago after his 21-year-old daughter died of cancer.
So far, only Colorado's law has taken effect, a little over a month ago. The
Goldwater Institute, a conservative nonprofit that defends states' rights,
created the model legislation for the new laws. While it has received word of
interest, no patients have yet formally tried to receive an experimental drug
under the new law, the institute said.
Under FDA rules for drug testing, Phase One, the first studies to use human
subjects, is quite limited in the number of patient participants (typically 20
to 80, according to the FDA website on the drug approval process). This first
step is intended to determine the drug's most frequent side effects and how the
drug is metabolized and excreted.
If Phase One doesn't reveal unacceptable toxicity, the drug can be approved
for Phase Two trials, where the emphasis is on testing the effectiveness of the
drug. This stage can involve a few dozen to 300 patients. If the drug passes
muster, it goes onto Phase Three, which gathers additional evidence on safety
and effectiveness and involves from several hundred to 3,000 subjects.
In the Leclaire brothers' case, those selected for the trial had to still be
ambulatory most of the time, but with the expectation that their walking days
would end within a year, said Jenn McNary, the boys' mother. Max fell down
occasionally, but he still didn't need the wheelchair most of the time. Austin
no longer qualified.
So even as Austin has watched Max get stronger from the drug treatments, he
wonders what motor skill he will lose next. And while he hopes s one day to
earn degrees in mechanical engineering and zoology, he is aware that those with
his condition rarely survive their 20s.
"I'm glad that Max has (the treatments), and he's proving that it does
work, and I should have it, too," Austin said by phone from home.
"But it's also unfair. ... I'm just really upset that the FDA won't
approve the drug, and it's their fault that someone might die."
The FDA has taken no official position on the new laws. "While the
agency is supportive of patients' access to experimental new treatments, the
FDA believes that the drug approval process represents the best way to assure
the development of safe and effective new medicines for patients," an FDA
statement said.
Although there are already provisions in place that allow for expedited
approval of drugs and to make certain experimental drugs available to
individuals prior to final approval, the Goldwater Institute insists that even
those procedures take too long for a person whose time is running out. "A
lot of patients don't have five or six months" that those procedures take,
said Victor Riches, a Goldwater spokesman.
The FDA said it receives about 550 applications a year from drug companies
to supply drugs to individuals before final approval and agrees to nearly all
of them.
But that doesn't account for patients who have been turned down by
manufacturers, such as Holly Singh, a Texas second-grade teacher whose
14-month-old daughter, Harper, has spinal muscular dystrophy, which leaves her
incapable of picking her head up, crawling or rolling over. Without help, her
life expectancy is quite limited.
Singh applied to Isis Pharmaceuticals, developer of the promising drug,
ISIS-SMN-rx, which is soon to enter Phase Three clinical testing, for early
access to the drug. In turning down her request, Isis chairman Stan Crooke
raised the possibility that granting it could have prolonged the overall
testing program and delayed the drug's approval for other patients. He also
said that all the safety concerns had not been fully addressed.
Singh's correspondence with Crooke demonstrates her desperation. She wrote,
"What kind of mother would I be if I just told my child, 'I'm sorry that
there's a drug, but unfortunately you can't have it. You just need to suffer a
little while longer.' "
While sympathetic to the situation of individual patients, the
pharmaceutical industry has been far from enthusiastic about the right-to-try
laws.
"We have serious concerns with any approach to make investigational
medicines available that seeks to bypass the oversight of the Food and Drug
Administration and clinical trial process, which is not in the best interest of
patients and public health," said Sascha Haverfield, vice president of
scientific and regulatory affairs for the Pharmaceutical Research and
Manufacturers of America. He suggested that medical providers, the
pharmaceutical industry and FDA should seek ways to improve access to clinical
trials.
Critics of the new laws contend that Phase One trials are too limited to
assure that a drug can be safely used. "Safety (in Phase One) is tested in
only the crudest way you can imagine, making sure it doesn't kill people,"
said David Gorski, an associate professor of surgery at Wayne State University
and the editor of the Science-Based Medicine blog, which has been critical of
right-to-try laws. Even for terminally ill patients, Gorski argues, the risks
are too great based solely on Phase One trials.
"They say it couldn't get any worse." Gorski said. "Well,
yes, it can get worse. If there's anything worse than dying of a terminal
disease, it's added suffering and potentially cutting the time you have
left."
According to a January article in the journal Nature Biotechnology, only 16
percent of investigational drugs that complete Phase One clinical trials
ultimately gain FDA approval.
Still, patients and families say they feel that they should be free to take
the chance given that the alternative is death. "I should be able to take
the risk of whether or not it would help," said Austin Leclaire.
"It's my life."
