[Ip-health] Canada's federally funded program aimed at bringing rare gene and cell therapies to Canadians at an affordable price.

James Love james.love at keionline.org
Mon Oct 28 07:06:16 PDT 2019


This story, by Kelly Crowe for CBC News, describes a very interesting
initiative in Canada:  "a new federally funded program aimed at bringing
rare gene and cell therapies to Canadians at an affordable price."

The treatment in the story is Glybera, "the world's first approved gene
therapy, was developed in Canada but only approved for sale in Europe."
The price was $1 million per treatment in Europe, and was withdrawn from
the market, given a lack of demand.

* Glybera treats a rare and potentially deadly genetic disorder called
lipoprotein lipase deficiency, or LPLD. Canada has the world's largest
population of LPLD patients clustered in the Saguenay region of Quebec,
where an ancestor with the genetic mutation settled several hundred years
ago.

* Stanimirovic said the fact that Canada has such a large population of
LPLD patients was an important factor in deciding to give Glybera a second
chance.

* "This gene mutation is very prevalent in Canada compared to other places
in the world," she said. "For us, it was almost calling us to do something
on the manufacturing side for this particular gene therapy."

* The ultimate plan is to develop public sector manufacturing capacity to
create not just an affordable version of Glybera but other gene and cell
therapies as well. The total federal funding for six projects including
Glybera is estimated at about $80 million over seven years.


https://www.cbc.ca/news/health/glybera-lpld-rare-drug-orphan-disease-nrc-cbc-price-1.5312177

Canadian breakthrough that became the world's most expensive drug, then
vanished, gets second chance
Kelly Crowe · CBC News
Oct 17, 2019

Glybera, the world's first approved gene therapy, was developed in Canada
but only approved for sale in Europe. The drug was pulled from the market
after only two years and a single commercial sale. At the time, Glybera was
the world's most expensive drug, priced at $1 million for a one-time dose.
(Craig Chivers/CBC)

A made-in-Canada medical breakthrough that disappeared from the market
because it wasn't profitable is being revived by the National Research
Council of Canada (NRC).

It's the latest chapter in the saga of Glybera, the world's first approved
gene therapy, which also became the world's most expensive drug after it
was licensed to a Dutch company and priced at $1 million for a one-time
dose.

Glybera treats a rare and potentially deadly genetic disorder called
lipoprotein lipase deficiency, or LPLD. Canada has the world's largest
population of LPLD patients clustered in the Saguenay region of Quebec,
where an ancestor with the genetic mutation settled several hundred years
ago.

People with LPLD lack a critical enzyme that helps their bodies process the
fat from food. There is currently no available treatment and no cure. Those
with LPLD must avoid most dietary fat to try to prevent painful and
dangerous attacks of pancreatitis.

The decision to re-develop a Canadian version of Glybera is the result of a
serendipitous series of events, beginning when the NRC's director of
research and development for translational bioscience happened to be
watching CBC's The National  last November.

The National: The million dollar drug that patients can't access

How a Canadian medical breakthrough became the world's most expensive drug
— and then quickly disappeared

Dr. Danica Stanimirovic was in the process of selecting the first project
for a new federally funded program aimed at bringing rare gene and cell
therapies to Canadians at an affordable price. Then she saw CBC's feature
report telling the story of how Glybera was pulled from the European market
after only one commercial sale. The drug was never offered for sale in
Canada or the U.S.

Dr. Danica Stanimirovic is the director of research and development for
translational bioscience at Canada's National Research Council. She
selected Glybera as the first project for a new federal program to
develop affordable
versions of gene therapies after seeing a CBC News report on Glybera's
commercialization failure. (NRC)

"That really sparked some thinking," she said. "We really have the ability
to advance that."

So she picked up the phone and called Dr. Michael Hayden in Vancouver. He's
the scientist at the University of British Columbia and the BC Children's
Hospital whose team developed Glybera. Hayden said he was happy to get the
call.

"I was thrilled because this represented a unique response to solve a big
Canadian problem, particularly for families in Quebec. And I was just
thrilled that we could do something as a national effort to achieve this."

Made-in-Canada medical breakthrough

The Glybera story started at UBC in the early 1990s, when Hayden and his
team discovered the first genetic mutations that caused LPLD. The
researchers then developed a method to fix the malfunctioning gene and
allow patients to live a nearly normal life.

After doing the preliminary research, the Canadian discovery was licensed
to a Dutch company called uniQure, which took Glybera through the rigorous
clinical trial and approval process.

When the treatment was approved by the European Medicines Agency in 2012,
it made headlines as the world's first gene therapy — the first treatment
that could repair a faulty gene.

When it went on sale in Europe in 2015, Glybera quickly made headlines
again, this time as the "world's most expensive drug," priced at $1 million
for the one-time dose.

Dr. Sander van Deventer, uniQure's chief scientific officer, told CBC News
last year that the price was a business calculation based on the price of
other drugs that treat rare diseases. Many of those drugs cost more than
$300,000 per patient per year. Because Glybera is a one-time treatment that
keeps working for years, the $1-million price seemed reasonable, he said.

CBC News Interactives: The million dollar drug
A team of maverick scientists is trying to build a bootleg version of a
million-dollar drug
Less than two years later, the drug was pulled from the market after only
one commercial sale. uniQure has no plans to revive the therapy.


Dr. Michael Hayden, director of the Centre for Molecular Medicine and
Therapeutics at the Child & Family Research Institute in Vancouver, will be
leading the Canadian scientific team as they re-engineer Glybera. (Darryl
Dyck/The Canadian Press)

Although Hayden discovered the gene mutation and developed the early phase
of the treatment, he had no role in the commercialization of his discovery.
And that meant he also had no control over the price.

"You don't determine the outcome, you don't determine its costs," he said.
"I'd say what went wrong is that it was very hard to be able to make sure
that this got to patients at a reasonable cost."

Stanimirovic said the fact that Canada has such a large population of LPLD
patients was an important factor in deciding to give Glybera a second
chance.

"This gene mutation is very prevalent in Canada compared to other places in
the world," she said. "For us, it was almost calling us to do something on
the manufacturing side for this particular gene therapy."

LPLD is rare, affecting one or two out of every million people around the
world. But in the Saguenay region of Quebec, where the gene mutation has
been passed down through generations, the numbers are 30 times higher. Up
to one in 50 people in some communities are carrying the gene mutation.
Both parents must have the mutation for a child to inherit the disease.

'Astronomical' price in 'pharma-driven model'

The ultimate goal of gene therapy is to fix a genetic problem by giving the
patient a new gene. Specially engineered viruses are used to deliver the
repair gene to the patient's cells. The cost of manufacturing those viruses
is often cited as one reason for the high price of therapies. The need to
generate pharmaceutical shareholder profits is another factor.

"[Gene therapies] are usually targeted to very small patient populations,"
Stanimirovic said. "It's hard to make them in a typical pharma-driven model
because it drives the price of these therapies to astronomical levels."


The NRC has developed expertise in manufacturing viral vectors to deliver
gene therapies. (NRC)

At its facility in Montreal, the NRC has already developed expertise in
producing viral vectors that act as the delivery system for gene therapy.
Because the scientists will be re-engineering Glybera using new viral
vectors, and improving the therapy, any remaining patents will not be an
obstacle, Stanimirovic said.

The ultimate plan is to develop public sector manufacturing capacity to
create not just an affordable version of Glybera but other gene and cell
therapies as well. The total federal funding for six projects including
Glybera is estimated at about $80 million over seven years.

"Our goal is to create new partnership models that will create therapies
that are more accessible and more affordable," said Stanimirovic. "We hope
we can do that through public partnership or public/private partnerships.
So the end goal is to really, through this project, develop Canadian
capacity to take on subsequent gene therapies."

Hayden called the plan a "beautiful Canadian story."

"Now we have to translate this into something that will truly be effective
for patients in a limited time frame and I'm so excited to do this."

We've been fighting for 10 years with doors closed. The possibility that
something is coming is encouraging, but yes, it's long.

For patients suffering from LPLD, the wait is frustrating.

Felix Lapointe, a 10-year-old from Repentigny, Que., was five weeks old
when his mother learned the terrible news that her son had the potentially
deadly genetic disease.

Brenda Potter helps her 10-year-old son Felix Lapointe assemble a jigsaw
puzzle. Felix has LPLD, a potentially deadly genetic disease that currently
has no available treatment and no cure. Potter is encouraged that the NRC
is planning to re-invent Glybera, but she says it's still going to be a
long wait, at least five years, before the first clinical trials. (CBC)

Because there is no treatment available right now, he's managing the
disease through a strict diet to reduce the risk of dangerous pancreatic
attacks. He will have to wait another five years for the first clinical
trials of the re-invented Glybera.

"We'd like it to happen tomorrow morning," said Brenda Potter, Felix's
mother. "Still, we're a little used to this. We've been fighting for 10
years with doors closed. The possibility that something is coming is
encouraging, but yes, it's long."

ABOUT THE AUTHOR

Kelly Crowe
Medical science

Kelly Crowe is a medical sciences correspondent for CBC News, specializing
in health and biomedical research. She joined CBC in 1991, and has spent 25
years reporting on a wide range of national news and current affairs, with
a particular interest in science and medicine.


-- 
James Love.  Knowledge Ecology International
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