Most doctors will never see a case
of Fabry, but the disease is changing how we decide
on coverage of drugs for rare diseases and challenging
Canada's regulatory institutions to finally come up
with tenable solutions.
A coalition of pharmaceutical companies
along with CIHR and the FRSQ (Quebec's research body)
recently formed to conduct a post-marketing study of
treatments for Fabry disease. Although the research
sights have yet to be finalized, activity in this long
neglected area is welcome.
Fabry disease is a genetic disorder
caused by a deficiency of the enzyme alpha-galactosidase.
It affects about 300 Canadians and produces a range
of progressively worsening symptoms, including chronic
pain, chronic kidney disease, heart disease and strokes.
Symptomatic treatment for complications of the disease
was all that was available until Genzyme Corporation
got approval for its enzyme replacement drug Fabrazyme
and Shire Biochem for their product TKT in 2004. These
were rays of hope.
HOPE
CRUSHED
A number of provinces covered the drugs until the Common
Drug Review (CDR) stepped in and recommended that provincial
drug plans not list them. The CDR noted that no cost-effectiveness
evaluation was provided. The bigger concern, however,
was about the quality and amount of data. The CDR objected
to the lack of evidence on clinical endpoints, the small
number of patients and the limited length of follow-up,
understandable problems for a disease that affects so
few and a treatment that costs almost $300,000 per patient
per year. Patient outcry led to a reassessment by CDR
but they didn't budge on their "do not list" recommendation.
Dr Andreas Laupacis, former Chair
of the Canadian Expert Drug Advisory Committee (CEDAC),
the expert assessment arm of the CDR, told a forum organized
by the Canadian Organization for Rare Diseases in October
2006, that the drug never had a chance. "It was clear
that based on our criteria, even before the review,
Fabrazyme would not meet standards of cost-effectiveness,"
he said. "It becomes a societal policy decision whether
we, as a society, want to treat these drugs and patients
differently because of the special issues in dealing
with rare disorders. CEDAC is not appropriately constituted
to make those societal decisions."
WAVE
OF OUTRAGE
At the same time as the Fabry debacle, the health ministers
of all Canadian provinces and territories minus Quebec
established a task force to develop and implement a
National Pharmaceutical Strategy (NPS). While drugs
for rare disorders were not on the original list of
NPS priorities, the controversy around Fabry disease
prompted ministers to promise "consistent national processes
and standards to ensure that Canadians with rare, severe
and progressive or life-threatening diseases have access
to appropriate and affordable treatments."
The three-year $100 million post-marketing
study was announced shortly afterwards. On the up side,
patients who were previously receiving the drugs now
have some assurance their costs will be covered for
at least three years. In the absence of government coverage,
Genzyme had been providing its drug Fabrazyme to Ontario
patients free of charge.
But there are serious concerns
about the study design. "We need a different way of
assessing drugs for rare diseases," says Dr Durhane
Wong-Rieger, President of the Canadian Organization
for Rare Disorders, "though this particular study is
not a template for what I'd like to see in the future."
She adds the study is neither long enough nor large
enough to provide the answers needed to satisfy the
questions raised by the CDR.
Dr Wong-Rieger is sceptical that
the issues around Fabry disease will be any closer to
resolution three years from now. It's still a small
patient population and a short followup. "The manufacturers
keep international patient registries to follow outcomes
of people on their drugs," she says, "which have the
numbers, but government is reluctant to use this proprietary
information as a basis for decision-making." We need
ways to get over that impasse rather than create a new
set of insufficient data.
In the meantime Fabry patients
can take some solace in the largely positive findings
in the largest-ever study of Fabrazyme, published in
the January 16 Annals of Internal Medicine. The
double-blind study, which included a site in Halifax,
found that taking the drug halved the risk of the disease
progressing.
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