Pompe disease: a case study of the development of a successful treatment for a rare disease

1. Pompe disease: a case study of the development of a successful treatment for a rare disease Kevin O’Donnell

2. This talk will cover… • What is Pompe disease? • The 70-year march • The roles of scientists, industry and patients • Enzyme Replacement Therapy

3. The Hollywood version “Don’t hope for a miracle. Make one up.”

4. Joannes Cassianus Pompe • Dutch pathologist • Published description of disease in 1932 • Identified it as a glycogen storage disease • Joined Dutch resistance in 1940

5. April 14, 1945

6. A puzzle • Glycogen storage But • Normal glycogen metabolism enzymes present

7. Christian de Duve • 1955 - Researching effect of insulin on the liver • Discovered intracellular compartments • Lysosomes • Nobel prize in 1974

8. Lysosomes

9. Henri-Gery Hers • Co-worker of de Duve • Interested in glycogen storage disease • Alpha-glucosidase deficiency • A lysosomal enzyme • Lysosomal Storage Disease concept - 1965

10. The Turning of the Tide • 1991 -Arnold Reuser and Ans van der Ploeg • Showed enzyme replacement therapy could work • Mannose-6-phosphate

11. Enzyme Replacement Therapy (ERT)

12. Patient groups • Patient groups organised across world • Championed Dutch work • Funding lifeline • Industry interest generated

13. 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

14. 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.

15. Novazyme

16. 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?

17. 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)

18. 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

19. 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.”

20. 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.”

21. 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.”

22. Resources www.pompestory.blogspot.com www.pompe.org.uk www.pompe.com www.worldpompe.org www.amda-pompe.org

23. 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