Isaac McFadyen

POSTED AT 1:44 AM EDT ON 29/04/06

‘We're looking for a lifeboat'
LISA PRIEST

Globe and Mail Update

The parents of Isaac McFadyen have two choices. They can move to England
where a drug to treat their son's rare disease is funded by government —
at a staggering cost of $300,000 to $1-million per patient annually — or
they can stay in Canada and watch him be ravaged by the inherited
metabolic disorder.

The two-year-old Ontario boy is already suffering from the effects of
Maroteaux-Lamy syndrome: a piece of his skull and a portion of vertebrae
in his neck were removed earlier this month after they began compressing
his spinal cord. Isaac's corneas are clouding, his forehead protrudes
and he has an umbilical hernia ("outie" bellybutton).

The only drug available to treat the progressive disease, known by the
trade name Naglazyme, is so expensive that even its U.S.-based developer
and manufacturer, BioMarin Pharmaceutical Inc., acknowledges no patient
can afford it.

“For the average citizen, no matter what country you are in, it's
impossible to pay for this out of pocket,” Steve Aselage, senior
vice-president of global commercial operations for BioMarin, said in an
interview from Novato, Calif. “For most of the world, you need the
government to step up and pay for the product.”

The drug is used to treat mucopolysaccharidosis type VI, or MPS VI for
short, a disease so rare it's estimated only three to 10 Canadians have
it. In developed countries, there are an estimated 1,100 sufferers,
virtually all of whom will experience severe disability and shortened
life spans.

In most countries where Naglazyme is licensed, such as those in the
European Union, governments cover the drug's cost. In the United States,
it is largely funded by private insurance.

But in Canada, there is no policy for “orphan drugs” like Naglazyme —
medications for rare diseases, the incidence of which varies by country
— and no way for people like the McFadyens to afford such costly therapies.

The EU, the United States, Japan, and Australia all have some form of
orphan-drug policy. While the U.S. policy doesn't necessarily provide
access to rare drugs, it has been successful in providing incentives to
pharmaceutical companies to find treatments for rare diseases.

Whether it involves fast-tracking drugs for rare diseases, providing tax
incentives for pharmaceutical companies to develop treatments, or
extending market exclusivity for drug manufacturers, these countries
have found ways to deal with a problem that threatens small numbers of
people in the most devastating of ways.

People with MPS VI, for example, are missing an enzyme called
arylsulfatase B, needed to break down carbohydrates known as
glycosaminoglycans. The carbohydrate builds up in the body's cells and
many organs are affected.

Signs of the disease include stunted growth, enlarged tonsils and
adenoids that cause breathing problems, poor mobility, and dramatic
changes in facial features, including a flat nose and large head. Once
sufferers reach their teens, they often require heart-valve surgery.

In England, a national advisory group aims to help health-care providers
by assuring a cash flow to support rare and expensive treatments. The
group has approved the funding of Naglazyme and a small group of
patients recently began receiving weekly intravenous treatments in
London and Manchester.

“We hope that at a minimum, it will halt the disease process,” said Ed
Wraith, consultant pediatrician at Royal Manchester Children's Hospital,
where some of the 12 patients in that city have begun treatment. The
drug is given for life. Until Naglazyme became available, there was no
approved treatment for the disease.

“Canadian patients with rare diseases are the last people in the
developed world to gain access to drugs,” said Kirsten Harkins,
executive director of The Canadian Society for Mucopolysaccharide and
Related Diseases Inc.

“There are no clear policy guidelines in terms of licensing or funding
them in Canada.”

That could change in June, when a report on expensive drugs for rare
diseases is to be presented at a meeting of Canada's health ministers,
marking the first time the country has attempted to deal with the
orphan-drug issue.

“The important thing for the really expensive drugs is that we have a
national approach,” said Bob Nakagawa, assistant deputy minister for
pharmacare for British Columbia, whose government is co-chairing the
task force in June with Health Canada.

“If [provinces] have different standards, then do we force patients to
move to the province that covers them? Is that something we want people
to do?”

In the case of the McFadyen family, it isn't just a case of travelling
to another province but of uprooting their idyllic life in the town of
Campbellford, Ont., and crossing the Atlantic with young Isaac and their
five-month-old son, Gabriel.

Andrew McFadyen, a 28-year-old elementary school teacher in Kingston,
and his wife, Ellen Buck-McFadyen, a public health nurse, feel they have
no choice but to look for employment overseas to get treatment for their
son, Isaac.

“We're optimistic that even with the limitations he's had, they aren't
affecting his quality of life,” said Ms. Buck-McFadyen, 28. “We have to
get him on the enzyme-replacement therapy, at least to slow down the
progression of the disease.”

Because Mr. McFadyen is eligible for British citizenship through his
Welsh mother, he only needs to find a job in England and maintain
residency for a period of time for young Isaac to receive the drug,
where it is currently offered in specialized centres in London and
Manchester.

Even though the overseas move is onerous, the couple feels lucky that,
unlike others, they at least have a shot at being able to obtain
treatment for Isaac.

They are making plans to move to England this summer, taking their
infant son and his sandy-haired, high-spirited big brother, Isaac, with
them.

“We're looking for a life boat,” Mr. McFadyen said. “We're just so sure
that we're going to get him on this enzyme replacement therapy and it's
going to help. If we spent any real time thinking about it, it would be
terrifying.”

While Naglazyme can technically be obtained under Health Canada's
special-access program, patients are still faced with having to cover
its enormous costs. No hospital or provincial government funds it. Under
the special-access program, patients with serious or life-threatening
conditions can obtain unlicensed drugs when conventional therapies fail,
are unsuitable or are unavailable, so long as no licensed alternative is
available.

(One person applied for the enzyme-replacement therapy, but later put
the application on hold, said Health Canada spokesman Christopher Williams.)

Joe Clarke, director of the genetic metabolic diseases program at
Toronto's Hospital for Sick Children, and Isaac's physician, wrote a
commentary in the Canadian Medical Association Journal in January,
entitled “Is the current approach to reviewing new drugs condemning the
victims of rare diseases to death? A call for a national orphan drug
review policy.”

Part of the problem with assessing these types of drugs is that the
diseases are so rare that it's difficult to run a clinical trial study
with enough patients to scientifically prove whether the drug is effective.

“What I was proposing was an orphan-drug review policy,” said Dr. Clarke
of his commentary, which listed 19 therapies for various rare diseases
and their costs. Such a policy is required, he said, because it is
virtually impossible to assess the cost-effectiveness of treatments of
rare diseases, using conventional criteria. A key component would be a
commitment to evaluate patients through registries to collect clinical
information.

Durhane Wong-Rieger, president of the Canadian Organization for Rare
Disorders, said that without a national plan, Canadians are struggling,
trying to access treatment for their rare diseases and in many cases,
not getting them at all.

Though individual drugs are costly, they don't necessarily amount to a
big financial hit to government, due to the low numbers of patients who
require them.

“From an ethical point of view, it's imperative for the government to
fund treatments that are life-saving for which there isn't anything
else,” she said.

Other countries have found that such a policy can prompt pharmaceutical
companies to discover treatments for rare diseases. In the decade before
the United States created its Orphan Drug Act, only 10 products for rare
diseases came to market. Since the 1983 act, 286 products have been
created, the Food and Drug Agency reports.

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