Transcript Pompe disease - ESRC Genomics Network

Pompe disease:
a case study of
the development
of a successful
treatment for a
rare disease
Kevin O’Donnell
This talk will cover…
• What is Pompe disease?
• The 70-year march
• The roles of scientists, industry and
patients
• Enzyme Replacement Therapy
The
Hollywood
version
“Don’t hope for a
miracle. Make one
up.”
Joannes Cassianus
Pompe
• Dutch pathologist
• Published
description of
disease in 1932
• Identified it as a
glycogen storage
disease
• Joined Dutch
resistance in 1940
April 14, 1945
A puzzle
• Glycogen
storage
But
• Normal
glycogen
metabolism
enzymes
present
Christian de Duve
• 1955 - Researching
effect of insulin on
the liver
• Discovered
intracellular
compartments
• Lysosomes
• Nobel prize in 1974
Lysosomes
Henri-Gery Hers
• Co-worker of de Duve
• Interested in glycogen
storage disease
• Alpha-glucosidase
deficiency
• A lysosomal enzyme
• Lysosomal Storage
Disease concept - 1965
The Turning of the Tide
• 1991 -Arnold
Reuser and
Ans van der
Ploeg
• Showed
enzyme
replacement
therapy could
work
• Mannose-6phosphate
Enzyme Replacement
Therapy (ERT)
Patient groups
•
•
•
•
Patient groups organised across world
Championed Dutch work
Funding lifeline
Industry interest generated
To market, to market…
• Scale up needed for trials
• Pharming produced enzyme in rabbit milk
• Other companies then interested – including
Genzyme
• Succesful trials
• Genzyme bought out everyone else – scaled
up for market
• Patient groups championed development
Clinical Trial Results
I had some good videos of the clinical trial
results here which, due to patient
confidentiality, I cannot make widely
available.
They showed though that the treatment
was a success – heart size was
reduced and muscle function recovered.
Novazyme
How not to do it
• Genzyme paid $137 million for
Novazyme
• Product did not work
• Industry/scientist/patient group model =
how to do it
• Novazyme = how not to do it
• Delayed development?
Scale-up and Approval
• Genzyme scale up production via cell
culture
• Expanded trials
• 2006 – approved as a medicine in US
and Europe
• Available on NHS (but not in Scotland)
Timeline
1932 - JC Pompe discovers disease
1965 - H-G Hers explains disease
1991 - Reuser and van der Ploeg
demonstrate treatment
1999 - first clinical trials
2006 – Approval as a medicine
What the patients say
Hillary, 33, Oregon
“ERT has helped me stabilize my
pulmonary function and regain
some strength.
After a couple years on ERT I
started skiing again, which I
had given up a few years
before.”
What the patients say
Helen, Australia
“Myozyme changed my life from
spending hours a day on the Bi
pap to not needing it at all during
the day.
I have been able to get back into the
community, get out in the
garden, go for a drive and the
treatment allows me to
undertake a conversation without
losing by breath.
My future was so close to being put
in a nursing home.”
What the patients say
Phoenix, 8, Florida
“At the start of treatment Phoenix's
heart was very enlarged…The
Myozyme fixed that and today his
heart is described as "normal"!
We are extremely happy to be able to
spend our time with this little boy
who is quickly becoming a young
man.
However, from a skeletal muscle
standpoint he has not seen any
improvement. He is still very weak and
has to use a ventilator 24hrs a day
to breathe.”
Resources
www.pompestory.blogspot.com
www.pompe.org.uk
www.pompe.com
www.worldpompe.org
www.amda-pompe.org
Conclusions
• “Chance favours the prepared mind”
• Breakthroughs can come from
unexpected areas
• The pharmaceutical industry is a good
servant but a poor master
• Patient groups can make a difference