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-6-phosphate

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