Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

What you can read here is the story of the development of enzyme replacement therapy (ERT), the first effective treatment for Pompe disease. It is an incredible story, rich with events, characters and science. Above all, it is the story of an international community of scientists, doctors, patients and companies, working together towards a common goal.

It is not a story that features in Geeta Anand's book, The Cure , or the film based on it, Extraordinary Measures despite the fact that they are ostensibly about the development of ERT for Pompe ( you can link straight to the relevant articles covering the events described in the book and film here, here and here).

This blog represents my small attempt to set the record straight and to give the story back to its rightful owners - the international Pompe community. It is written here in roughly chronological order i.e. you'll need to start at the bottom of the April 2009 archive page and work your way up.

It is also a personal account and, although I've tried to make it as objective as possible, there is an inevitable degree of subjectivity. For that reason I have included contributions from other members of the worldwide Pompe community and would be delighted to receive more. Feedback is also welcome.

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Sunday, 3 January 2010


I didn't see this one coming - though they, arguably, saw me.

Let me say at the outset that the Novazyme story is not one in which anyone (including me) emerges with any credit at all.  It was, in my view, a time and resource wasting piece of nonsense that quite possibly delayed the wider availability of a treatment for Pompe disease. That's only my own opinion, of course; you can judge for yourself.

I will now tell the story from the beginning. You may feel aggrieved at knowing the ending already. But think of it as watching a magic show. You know that what you're going to see unfold is an illusion but the entertainment is in trying to work out how it was done.

After some rumblings and rumours, Novazyme burst onto the scene in October 2000 via a press release announcing that they had US 'orphan disease' designation for a planned Pompe disease treatment.

A website followed in early November 2000, which was 'patient friendly' and generated some discussion about Novazyme and what they were doing.  My own thoughts at the time, as published on GSDNet, were:

What I've personally found difficulty doing here is to separate my opinion of John Crowley (a good guy and one of us) from Novazyme (a hungry new company competing in a tough market). In other words, we need to give Novazyme the same critical appraisal as we have given Genzyme and Pharming.I think it's important to do this. Having tried to do so, I find I'm left with a number of unanswered questions about Novazyme. These principally boil down to 'where's the beef'.

They say that their method of phosphorylating alpha-glu leads to increased uptake. That's good - but where's the evidence? They mention animal studies - but these don't appear to be published. Are they going to be published and, if so, where and when. If not, why not? The alarm bells set ringing by this rang a good deal louder when a saw the graph on their website. It shows uptake of 'well phosphorylated' enzyme versus 'poorly phosphorylated' enzyme. The phosphorylated enzyme does much better. The
conclusion that we're invited to draw is that this is a comparison of Novazyme's product against..well, against what exactly? Pompase? the transgenic enzyme? Bog-standard unphosphorylated alpha-glu? We are not told which, sceptic that I am, leads me to think that the last option is the most likely answer. I hope I'm wrong - only Novazyme can tell us and they've chosen not to.

The second thing we need to consider is this. Given that the existing enzyme brings levels back up to normal in Pompe's patients, would any increase in uptake make any difference clinically? Is there any evidence from animal models that this is the case?

These are the questions we need answered, I think.

I should have printed that out and stuck it on my wall as a reminder not to let my enthusiasm become detached from the evidence.

Naturally, I was keen to get the story from the horse's mouth and eventually had a telephone conversation with John in February 2001. What he told me sounded astonishing.  
He said that Novazyme had already carried out a fibroblast (cell culture) study comparing the Novazyme super-enzyme against the equivalent to that used in the YT Chen study. They had found that their enzyme was 99% phosphorylated, compared with only 3% for the "Synpac equivalent". This meant, John told me, that treatment could be carried out with only one hundredth of the Synpac dose - or one thousandth of the Pharming one. Many more patients could therefore be treated with the same amount of enzyme - because the Novazyme product was so much better!
John went on to say that they had considered 3 different contractors for manufacturing their product but had concluded that the best way forward was to construct their own. Their target was to begin clinical trials by Autumn 2001. I was slightly sceptical about all this - if something sounds too good to be true, it generally is. However, John then said something that brought me on board: "Kevin, no-one will ever be deprived of this drug because they cannot afford it."

This had been a real concern for the patient community - the Genzyme Gaucher treatment was, after all, the most expensive drug supplied by the UK's National Health Service. But here was someone talking our language! One of us! In charge of a new go-ahead company with a fantastic product! It just couldn't get any better than that, could it?

In February 2001, Novazyme announced the opening of their new facility in Oklahoma. Hot on the heels of that, in April 2001, Novazyme announced successful results using an animal model. This showed an 'unprecedented' response to ERT using the Novazyme product. Just two doses had cleared accumulated glycogen from the mice and restored muscle function!

This was beginning to look like business. So when Novazyme offered me the opportunity to visit them on Oklahoma (along with Randall House) I jumped at the chance. Who wouldn't?

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